mercaptopurine and Leukemia--Lymphoid

Methotrexate (MTX) and 6-mercaptopurine (6MP) have been used since 30 years in the maintenance treatment of acute lymphoblastic leukemia (ALL) of childhood. A synergistic effect of this combination was demonstrated in mouse and childhood leukemia. In this article an overview is given of our investigations, concerning the biochemical basis of this synergism. This synergism is caused by a selective inhibition of the purine de novo synthesis in malignant lymphoblasts by MTX, associated with an enhanced intracellular uptake of 6MP. Pharmacokinetic studies of MTX in various schemes of prophylactic central nervous system treatment in ALL are discussed. Treatment with 24-hr infusions of MTX in a dosage of 5 g/m2, as recommended in the new BFM-86/SNWLK ALL VII protocol, seems to be optimal. Pharmacokinetic studies of intravenous 6MP infusions demonstrated a good cerebral fluid penetration. Exploiting the synergistic action of the combination of MTX and 6MP may offer an improvement of the prophylactic central nervous systems treatment in ALL in the future, using intravenous administration of both MTX and 6MP.

Topics: Child; Drug Synergism; Humans; Leukemia, Lymphoid; Mercaptopurine; Methotrexate

Topics: Bone Marrow Diseases; Child; Drug Resistance; Female; Guanine Nucleotides; Humans; Leukemia, Lymphoid; Male; Mercaptopurine; Methyltransferases; Thionucleotides

This article reviews current chemotherapy of childhood acute lymphoblastic leukemia, with particular emphasis on the pharmacology of the drugs used. In the perspective of the overall treatment plan, the use, mode of action, toxicity and pharmacology of prednisone, vincristine, L-asparaginase, cyclophosphamide, 6-mercaptopurine, methotrexate and cytosine arabinoside are reviewed. Issues relating to central nervous system prophylaxis, drug compliance, drug resistance, and treatment failure are considered.

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Central Nervous System Diseases; Child; Cyclophosphamide; Cytarabine; Humans; Leukemia, Lymphoid; Mercaptopurine; Methotrexate; Patient Compliance; Prednisone; Vincristine

Topics: Adolescent; Animals; Antineoplastic Combined Chemotherapy Protocols; B-Lymphocytes; Central Nervous System Diseases; Child; Child, Preschool; Female; Humans; Infant; Leukemia, Lymphoid; Leukocyte Count; Male; Mercaptopurine; Methotrexate; Mice; Prognosis; Recurrence; T-Lymphocytes

Topics: Adolescent; Adult; Asparaginase; B-Lymphocytes; Bacterial Infections; Child; Child, Preschool; Chromosome Aberrations; Chromosome Disorders; Diagnosis, Differential; Drug Therapy, Combination; Female; Humans; Infant; Leukemia; Leukemia, Lymphoid; Leukocyte Count; Male; Meningeal Neoplasms; Mercaptopurine; Methotrexate; Prednisolone; T-Lymphocytes; Testicular Neoplasms; Vincristine

Topics: Asparaginase; Child; Cyclophosphamide; Germany, West; Humans; Injections, Spinal; Leukemia, Lymphoid; Mercaptopurine; Methotrexate; Prednisone; Prognosis; Remission, Spontaneous; Vincristine

Topics: Alkylating Agents; Antibiotics, Antineoplastic; Antineoplastic Agents; Aziridines; Chlorambucil; Cyclophosphamide; Drug Evaluation; Humans; Leukemia, Lymphoid; Mannitol; Mercaptopurine; Nitrogen Mustard Compounds; Phenylalanine; Piperazines; Prednisolone; Thiotepa

Topics: Adrenal Cortex Hormones; Alkylating Agents; Animals; Antineoplastic Agents; Asparaginase; Choriocarcinoma; Dactinomycin; Female; Folic Acid Antagonists; History, 19th Century; History, 20th Century; Humans; Leukemia, Lymphoid; Lymphoma; Mercaptopurine; Neoplasms; Pregnancy

Current therapy has resulted in improved prognosis in previously untreated children with acute lymphocytic leukemia less than 16 years of age. The induction phase of chemotherapy should include the use of at least prednisone and vincristine. This combination should result in a hematologic remission in about 90 per cent of the patients. The efficacy of the addition of either L-asparaginase or daunomycin, the consolidation phase or the periodic readministration of induction drugs has not been established. Specific central nervous system treatment, early in the course of therapy, is an integral component of recently reported effective protocols. Several modalities of prophalytic central nervous system therapy have been utilized. These include cranial irradiation plus intrathecal methotrexate, craniospinal irradiation and intrathecal methotrexate alone. An encephalopathy syndrome has been reported as a complication in 10 to 66 per cent of these patients. The most effective form of central nervous system therapy, associated with the least toxicity, has not been established. Maintenance chemotherapy should include a combination of two or more drugs. Complications are numerous, and include hematopoietic depression, immunosuppression, overwhelming infections, and, possibly, the development of secondary primary cancers. In the most successful protocols maintenance chemotherapy has been administered for 3 years. Because of the potential significant toxicity there is a need to define the optimal duration of maintenance therapy. Psychological complications developing in a patient with a disease now considered a potential long term chronic illness, rather than a disease once considered universally fatal, are also discussed. The possibility of an immunologic deficiency allowing for the initial development of acute lymphocytic leukemia and the role of immunotherapy are presented. While the use of intensive combination chemotherapy and specific central nervous system prophylactic therapy have resulted in an improved prognosis in childhood acute lymphocytic leukemia, because of a significant incidence of failures, a standardized single form of therapy has not been established.

Topics: Asparaginase; Central Nervous System Diseases; Child; Cyclophosphamide; Daunorubicin; Drug Therapy, Combination; Humans; Immunotherapy; Infections; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Mercaptopurine; Methotrexate; Neoplasms, Multiple Primary; Prednisone; Psychology; Remission, Spontaneous; Vincristine

Topics: Alkanesulfonates; Amidines; Bone Marrow Examination; Chickenpox; Child; Child, Preschool; Cyclophosphamide; Drug Therapy, Combination; gamma-Globulins; Humans; Leukemia, Lymphoid; Male; Mercaptopurine; Methotrexate; Nervous System Diseases; Phenyl Ethers; Physician-Patient Relations; Pneumonia, Pneumocystis; Prednisone; Pseudomonas Infections; Recurrence; Testicular Neoplasms; Vincristine

Topics: Acute Disease; Allopurinol; Antineoplastic Agents; Child; Humans; Leukemia, Lymphoid; Lymphoma, Non-Hodgkin; Mercaptopurine; Methotrexate; Prednisone; Uric Acid; Xanthine Oxidase

Topics: Acute Disease; Adolescent; Adult; Aged; Antineoplastic Agents; Child; Child, Preschool; Female; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Male; Mercaptopurine; Middle Aged; Prednisone; Prognosis; Remission, Spontaneous; Vincristine

Topics: Adrenal Cortex Hormones; Alkylating Agents; Antibiotics, Antineoplastic; Antineoplastic Agents; Cytarabine; Drug Synergism; Drug Therapy, Combination; Fluorouracil; Hodgkin Disease; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Mercaptopurine; Methotrexate; Mitosis; Neoplasm Metastasis; Thymine Nucleotides

Topics: Asparaginase; Child; Cyclophosphamide; Cytarabine; Daunorubicin; Doxorubicin; Humans; Leukemia, Lymphoid; Male; Meninges; Mercaptopurine; Methotrexate; Neoplasm Metastasis; Prednisolone; Remission, Spontaneous; Testicular Neoplasms; Time Factors; Vincristine

Topics: Adult; Burkitt Lymphoma; Child; Cyclophosphamide; Cytarabine; Daunorubicin; Drug Combinations; Hodgkin Disease; Humans; Immunotherapy; Infections; Leukemia, Lymphoid; Leukemia, Myeloid; Lymphoma; Mercaptopurine; Methotrexate; Middle Aged; Nitrogen Mustard Compounds; Prednisone; Procarbazine; Prognosis; Remission, Spontaneous; Vincristine

Topics: Acute Disease; Adult; Age Factors; Antineoplastic Agents; Asparaginase; Child; Cytarabine; Daunorubicin; Drug Therapy, Combination; Female; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Methods; Methotrexate; Prednisolone; Recurrence; Remission, Spontaneous; Vincristine

Topics: Acute Disease; Antineoplastic Agents; Chlorambucil; Chlorine; Chronic Disease; Daunorubicin; Dimethoate; Drug Therapy, Combination; Ethylamines; Glucocorticoids; Humans; Immunoglobulins; Immunosuppression Therapy; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Leukocyte Count; Lymphocytosis; Mercaptopurine; Methotrexate; Prednisolone; Remission, Spontaneous

Topics: Acute Disease; Adult; Aged; Antineoplastic Agents; Blood Coagulation Disorders; Cell Transformation, Neoplastic; Daunorubicin; Humans; Immunotherapy; Leukemia; Leukemia, Lymphoid; Mercaptopurine; Middle Aged; Mitosis; Prednisolone; Prednisone; Remission, Spontaneous; Vincristine

Topics: Asparaginase; Blood Transfusion; Cytarabine; Daunorubicin; Humans; Immunotherapy; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Leukocytes; Meninges; Mercaptopurine; Methotrexate; Prednisone; Remission, Spontaneous

Topics: Adrenal Cortex Hormones; Adrenocorticotropic Hormone; Animals; Antineoplastic Agents; Asparaginase; Central Nervous System Diseases; Child; Cyclophosphamide; Cytarabine; Cytopathogenic Effect, Viral; Daunorubicin; Humans; Kinetics; Leukemia, Experimental; Leukemia, Lymphoid; Meninges; Mercaptopurine; Methotrexate; Mice; Oncogenic Viruses; Patient Care Team; Remission, Spontaneous; Reverse Transcriptase Inhibitors; RNA Viruses; RNA-Directed DNA Polymerase; Time Factors; Vincristine

Topics: Asparaginase; Bacterial Infections; Central Nervous System Diseases; Child; Child, Preschool; Cyclophosphamide; Cytarabine; Daunorubicin; Drug Synergism; Hemorrhage; Humans; Immunotherapy; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Methotrexate; Mitosis; Neoplasms, Nerve Tissue; Prednisone; Remission, Spontaneous; Testicular Neoplasms; Uric Acid; Vincristine

Topics: Adult; Age Factors; Antineoplastic Agents; Child; Cyclophosphamide; Cytarabine; Follow-Up Studies; Humans; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Mercaptopurine; Methotrexate; Prednisone; Time Factors; Vincristine

Topics: Adenocarcinoma; Animals; Antineoplastic Agents; Bone Marrow; Bone Marrow Cells; Cell Division; Cyclophosphamide; Cytarabine; Female; Fluorouracil; Humans; Leukemia L1210; Leukemia, Lymphoid; Lymphoma; Melphalan; Mercaptopurine; Methotrexate; Mice; Multiple Myeloma; Neoplasms; Nitrogen Mustard Compounds; Prednisone; Pregnancy; Time Factors; Trophoblastic Neoplasms; Vinblastine

Topics: Child; Cyclophosphamide; Cytarabine; Daunorubicin; Drug Synergism; Humans; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Meningitis; Mercaptopurine; Prednisone; Remission, Spontaneous; Thioguanine; Vincristine

Topics: Animals; Antibiotics, Antineoplastic; Antineoplastic Agents; Asparaginase; Azaserine; Cell Division; Clinical Trials as Topic; Cyclophosphamide; Cytarabine; Disease Models, Animal; Drug Combinations; Humans; Kinetics; Leukemia L1210; Leukemia, Experimental; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Mercaptopurine; Methotrexate; Neoplasms; Prednisone; Remission, Spontaneous; RNA, Neoplasm; Vincristine

Topics: Adult; Antineoplastic Agents; Asparaginase; Carmustine; Child; Cyclophosphamide; Cytarabine; Cytosine; Daunorubicin; Drug Therapy, Combination; Hodgkin Disease; Humans; Immunotherapy; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Lymphoma; Male; Mechlorethamine; Mercaptopurine; Methotrexate; Nitrogen Mustard Compounds; Prednisolone; Prednisone; Procarbazine; Remission, Spontaneous; Vincristine

Topics: Adolescent; Adult; Antineoplastic Agents; Central Nervous System Diseases; Child; Cyclophosphamide; Cytarabine; Female; Guanidines; Humans; Hydroxyurea; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Leukopenia; Male; Mercaptopurine; Methotrexate; Middle Aged; Nitroso Compounds; Prednisone; Thrombocytopenia; Urea; Uric Acid; Vincristine

Topics: Busulfan; Cytarabine; Dexamethasone; DNA; DNA, Neoplasm; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Leukocytes; Mercaptopurine; Nucleic Acids; Prednisolone; Pyrimidines; RNA; RNA, Neoplasm

Topics: Acute Disease; Adrenal Cortex Hormones; Antineoplastic Agents; Asparaginase; Blood Transfusion; Cyclophosphamide; Diagnosis, Differential; Humans; Immunization; Leukemia; Leukemia, Lymphoid; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Mercaptopurine; Methotrexate; Nitroso Compounds; Prednisolone; Vincristine

Topics: Administration, Oral; Age Factors; Animals; Bone Marrow Examination; Child; Drug Synergism; Humans; Injections, Intramuscular; Leukemia, Lymphoid; Mercaptopurine; Methotrexate; Mice; Myelography; Prognosis; Time Factors

Topics: Anilides; Animals; Cell Division; Cyclophosphamide; Cytarabine; DNA, Neoplasm; Fluorouracil; Humans; Hydroxyurea; In Vitro Techniques; Leukemia; Leukemia L1210; Leukemia, Lymphoid; Mechlorethamine; Mercaptopurine; Methotrexate; Mice; Mitosis; Nitroso Compounds; Prednisone; Thymidine; Time Factors; Tritium; Vinblastine; Vincristine

Topics: Blood Cell Count; Blood Cells; Blood Transfusion; Child; Daunorubicin; Humans; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Mercaptopurine; Methotrexate; Prednisone

Topics: Antineoplastic Agents; Cyclophosphamide; Humans; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Mercaptopurine; Methotrexate; Prednisolone; Vincristine

Topics: Acid Phosphatase; Alkaline Phosphatase; Biochemical Phenomena; Biochemistry; Carbohydrate Metabolism; DNA; Folic Acid Antagonists; Glutathione; Heparin; Histamine; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Leukocytes; Lipid Metabolism; Lymphocytes; Mercaptopurine; Metabolism; Pathology; Peroxidases; Phagocytosis; Plasminogen; Pyrimidines; RNA; Thymidine; Trace Elements

Daily oral 6-mercaptopurine (6MP) is important in the treatment of childhood lymphoblastic leukaemia (ALL), but there is great inter-patient variability in the pattern of evident drug effect (myelosuppression) seen at a standard dose. In an attempt to reduce that variability the current practise in the United Kingdom for the last 4 years has been to escalate the amount prescribed in patients who do not experience cytopenias at 75 mg/m2. We undertook a study to see whether that strategy would increase the total dose of 6MP prescribed in such patients and whether it would alter the pattern of myelosuppression. Over a 6-month period we studied 44 children treated conventionally (without escalation) and compared them with another 44 (matched for sex) who were treated on the same protocol but where doses were increased in monthly 25% steps if 75 mg/m2 was tolerated without cytopenias. We then compared the two groups for the total dose of drug prescribed and the frequency and duration of neutropenia or thrombocytopenia. The median cumulative dose of 6MP received by the conventionally treated children (10,002 mg/m2) was not significantly different from that of the children treated with dose escalation (9,429 mg/m2). In a comparison of the 30 children who actually received inflated doses of 6MP with the 37 from the conventional cohort who would have been eligible to do so, it was again found that the cumulative median doses were similar (10,460 versus 10,916 mg/m2). There was a difference between the two groups in the pattern of myelosuppression -- the escalated group spent significantly more time off 6MP than did the non-escalated group (median 4.5 versus 3 weeks; P<0.005, 95% CI from -1 to -3). These findings imply that the method of dose escalation employed does not allow more 6MP to be prescribed in children tolerant of the standard dose. The chief effect seems to be to generate longer periods off therapy, and this could paradoxically decrease the anti-neoplastic activity of the drug. Alternative ways of prescribing should be explored.

Topics: Antimetabolites, Antineoplastic; Bone Marrow; Child, Preschool; Cohort Studies; Dose-Response Relationship, Drug; Drug Tolerance; Female; Humans; Infant; Leukemia, Lymphoid; Male; Mercaptopurine; Neutropenia; Thrombocytopenia

Children from the UKALL V trial were studied to assess the clinical importance of myelosuppression during uninterrupted 'maintenance' treatment of 'standard risk' lymphoblastic leukaemia. Those receiving daily 6-mercaptopurine and weekly methotrexate who were in first remission 20 months from diagnosis were divided into two groups on the basis of whether or not they had ever had an absolute neutrophil count of less than 0.5 x 10(9)/l recorded during maintenance treatment up to that time. Of 105 evaluable children, 45 (43%) became neutropenic at least once, and 60 (57%) did not. Seven (16%) of the neutropenic group subsequently relapsed compared with 27 (45%) of the remainder. This difference was still significant if the analysis was stratified by total treatment time (two or three years), age, sex, or diagnostic white cell count. Seven (16%) neutropenic children died in remission, compared with one (2%) of the non-neutropenic children. Therapeutic myelosuppression during standard maintenance treatment of 'standard risk' lymphoblastic leukaemia is associated with increased toxicity but a reduced risk of relapse. The unexplained improvement in long term survival in the United Kingdom in recent years may in large part be due to this.

Topics: Adolescent; Agranulocytosis; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Child; Child, Preschool; Female; Humans; Infant; Leukemia, Lymphoid; Leukocyte Count; Male; Mercaptopurine; Methotrexate; Neutropenia; Prognosis; Randomized Controlled Trials as Topic; Survival Rate; United Kingdom

From 1981 to 1983, 131 previously untreated patients with acute lymphoblastic leukemia (ALL) standard-risk group were entered to the protocol JCCLSG-S811. Of 119 eligible patients, 115 (96.6%) attained complete remission by treatment with prednisone (PRD) plus vincristine (VCR) or vindesine (VDS). After preventive central nervous system (CNS) therapy including 18 Gy cranial irradiation and three doses of intrathecal methotrexate (MTX), the patients were assigned randomly to the two maintenance chemotherapies, Regimen A and Regimen B. Regimen A (intermittent regimen) consisted of PRD (120 mg/m2/day by mouth for 5 days) plus 6-mercaptopurine (6MP) (175 mg/m2/day by mouth for 5 days) plus VCR (2.0 mg/m2 intravenously) alternating biweekly with MTX (225 mg/m2 intravenously). Regimen B (continuous regimen) consisted of 6MP (50 mg/m2/day by mouth) plus MTX (20 mg/m2/week by mouth) combined with pulses of PRD and VCR (the same dosages as Regimen A) every 4 weeks. As the late intensification therapy (LIT), five courses of high-dose MTX (2000 mg/m2 per dose per week intravenously for three doses every 12 weeks) with leucovorin rescue were administered to all patients who were in continuous complete remission (CCR) for more than 2 years. Sixty and 55 patients, respectively, were registered in Regimen A and B. The CCR rates in Regimen A and B were 75.1% +/- 5.8% (mean +/- 1 SE) and 49.7% +/- 7.3% (P less than 0.01) at 4 years, and 72.1% +/- 6.3% and 49.7% +/- 7.3% (P less than 0.05) at 5 years, respectively. In Regimen B, CNS and testicular relapses increased after 3 years of CCR. In addition, the patients in Regimen B had a much higher incidence of infections than Regimen A. The LIT did not seem to have important effects on the duration of CCR. From these data we conclude that the intermittent cyclic regimen of 6MP and MTX may be more effective as compared to the continuous administration of these drugs in the maintenance chemotherapy.

Topics: Antineoplastic Combined Chemotherapy Protocols; Child; Clinical Trials as Topic; Humans; Leukemia, Lymphoid; Mercaptopurine; Methotrexate; Nervous System Neoplasms; Prednisone; Random Allocation; Remission Induction; Time Factors; Vincristine; Vindesine

Topics: Child; Child, Preschool; Drug Administration Schedule; Humans; Kinetics; Leukemia, Lymphoid; Male; Mercaptopurine

Topics: Amsacrine; Antineoplastic Combined Chemotherapy Protocols; Child; Clinical Trials as Topic; Cytarabine; Drug Administration Schedule; Humans; Leukemia, Lymphoid; Mercaptopurine; Methotrexate; Random Allocation; Risk; Vincristine

Topics: Administration, Oral; Adolescent; Age Factors; Antineoplastic Combined Chemotherapy Protocols; Child; Child, Preschool; Clinical Trials as Topic; Humans; Infant; Injections, Intravenous; Leukemia, Lymphoid; Mercaptopurine; Methotrexate; Remission Induction

One hundred seventy-seven children with acute lymphoblastic leukemia (ALL) were admitted to a study designed to determine whether pulses of cytosine arabinoside (ara-C) and cyclophosphamide (cyclo) would improve disease-free survival (DFS). All patients received vincristine, prednisone, and asparaginase for remission induction, CNS prophylaxis with cranial irradiation and intrathecal methotrexate, and continuation therapy with 6-mercaptopurine plus methotrexate. Forty-seven of 101 patients with non-T ALL and 18 of 26 patients with T-cell ALL received ara-C/cyclo pulses every eight weeks during continuation therapy. The age, sex, and initial white cell count distributions were similar in both treatment groups. Patients with non-T-cell ALL had similar DFS with or without ara-C/cyclo pulses (36% versus 48%; P = 0.32). Ara-C/cyclo pulses significantly improved DFS in children with T-cell ALL (36% versus 0%; P = 0.015). Toxicities of the ara-C/cyclo pulses included reversible pancytopenia, drug induced fever, fever associated with neutropenia, and death in one patient from systemic candidiasis while neutropenic. This is the first clinical evidence to indicate that the combination of ara-C/cyclo used during continuation therapy is selectively beneficial in T-cell ALL.

Topics: Antineoplastic Combined Chemotherapy Protocols; Child; Cyclophosphamide; Cytarabine; Drug Evaluation; Humans; Leukemia, Lymphoid; Mercaptopurine; Methotrexate; Prednisone; Random Allocation; T-Lymphocytes; Vincristine

Topics: Adolescent; Asparaginase; Central Nervous System; Child; Clinical Trials as Topic; Electroencephalography; Humans; Injections, Intravenous; Injections, Spinal; Leukemia, Lymphoid; Leukocyte Count; Mercaptopurine; Methotrexate; Myelin Basic Protein; Prednisone; Prospective Studies; Random Allocation; Vincristine

Analysis of the results of United Kingdom Acute Lymphoblastic Leukaemia (UKALL) trials since 1972 showed that no improvement in remission or survival had been achieved over the 7 years up to 1979 for 1470 patients in trials UKALL II to VI. UKALL VII (1979-80) gave somewhat better results for a small group of good-prognosis patients. However, UKALL VIII, introduced in 1980, produced a 15-20% increase in 4-year disease-free survival compared with the best results of previous studies, despite a higher frequency of treatment-induced morbidity and mortality. Factors possibly contributing to this highly significant difference include the policy of continuing therapy without interruption during induction, a long course of intramuscular asparaginase over 3 weeks, full-dose mercaptopurine and co-trimoxazole during central-nervous-system prophylaxis, and the use of sustained maximum tolerated oral doses of mercaptopurine and methotrexate maintenance. An intensive sustained approach to chemotherapy in childhood ALL is needed, especially in the early stages of treatment.

Topics: Administration, Oral; Adolescent; Asparaginase; Child; Child, Preschool; Clinical Trials as Topic; Daunorubicin; Drug Combinations; Drug Therapy, Combination; Humans; Infant; Infant, Newborn; Injections, Intramuscular; Leukemia, Lymphoid; Mercaptopurine; Methotrexate; Random Allocation; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Between 1972-1977, 92 patients with acute lymphoblastic leukemia, between 0 and 14 years of age, were treated with C2-72 and D-74 protocols. Induction treatment consisted of prednisolone (PRED)-vincristine (VCR) with the addition of daunorubicin (prot. C2-72) or asparaginase (prot. D-74). In both protocols, preventive therapy on the CNS consisted of cranial irradiation (24 Gy) and 5 doses of methotrexate i.t. (MTX). For the maintenance phase in protocol C2-72, three combinations: mercaptopurine (MP)-MTX, MP-Ara.C and MTX-cyclophosphamide, were sequentially administered for 3 years, with reinductions of PRED-VCR every three months. In protocol D-74, only MP-MTX was used for 3 years; the random half of the patients also received "reinductions". In protocol C2-72, BCG was administered by scarifications for 2 years to patients in remission after 36 months; in D-74, the random-half patients received BCG and irradiated allogeneic blasts for one year. The other half of the patients received no other treatment. The overall disease-free survival rate is 45.6% with a duration of between 84 and 156 months. Only one death occurred after 7 years. In protocol C2-72, 9 of 26 initial patients (34.6%) and in protocol D-74, 33 of 66 initial patients (50%) are still alive, off treatment and with no sign of disease. Ten patients (10.8%) died in continuous remission of infection (8) or toxic encephalopathy (2); five deaths were caused by "Pn. carinii". The incidence of meningeal relapse was 11% and isolated testicular relapse in males 15.7%; moreover, in 6 of the 22 boys in remission, programmed testicular biopsy showed interstitial leukemic infiltrates. Analysis of initial risk factors permitted the establishment of a risk index (r.i.): in cases with a r.i. below 3 (76% of cases) the survival rate was 53%; in the group with a higher r.i. (24%), it was 22%. Further conclusions of this study were: the lack of effectivity of "reinductions" and immunotherapy and proof of a higher rate of relapses in males mainly owing to isolated testicular relapse.

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Asparaginase; BCG Vaccine; Child; Child, Preschool; Clinical Trials as Topic; Combined Modality Therapy; Cyclophosphamide; Cytarabine; Daunorubicin; Female; Humans; Immunotherapy; Infant; Infant, Newborn; Leukemia, Lymphoid; Male; Meningeal Neoplasms; Mercaptopurine; Methotrexate; Prednisolone; Random Allocation; Testicular Neoplasms; Vincristine

BHAC-MMP therapy, a combination of behenoyl-ara-C, mitoxantrone, 6-mercaptopurine and prednisolone, was applied to 49 patients with acute leukemia for remission induction. Complete remission was obtained in 6 out of 11 previously untreated patients (55%), and in 16 of 38 pretreated patients (42%). Median duration of complete remission was 41 weeks in previously treated patients, while 67% of untreated patients were still in complete remission. Most frequent side effects other than hematological toxicities were gastrointestinal disturbances, and GPT elevation etc., although most of these were not severe. In conclusion, BHAC-MMP therapy seems to be very promising for remission induction or for possible intensification treatment for acute leukemia.

Topics: Acute Disease; Adolescent; Adult; Aged; Anthraquinones; Antineoplastic Combined Chemotherapy Protocols; Clinical Trials as Topic; Cytarabine; Female; Humans; Leukemia; Leukemia, Lymphoid; Male; Mercaptopurine; Middle Aged; Mitoxantrone; Prednisolone

The Medical Research Council UKALL V trial for children with standard-risk acute lymphoblastic leukemia (ALL) (aged 1 to 14 years, leucocyte count less than 20 X 10(9)/L) was designed to determine whether the immunosuppressive effects of treatment could be reduced without sacrifice of antileukemic effect by alterations in the type of continuing therapy or in fractionation of cranial irradiation. Remission was achieved in 496 children on standard induction therapy, and 309 children received 24 Gy of cranial irradiation in ten to 16 fractions over 21 days, and 174 received 21 Gy in five to nine fractions over 21 days. The type of radiotherapy administered had no influence on relapse at any site or rate of death in remission. All 496 children were randomized to receive chemotherapy for 2 or 3 years with 6-mercaptopurine and methotrexate either as a continuous (group C) or a semicontinuous (group G) regimen or as a five-day pulse every 3 weeks (group I). All groups also received vincristine and prednisolone every 6 weeks. With a minimum follow-up of almost 7 years, patients in group I had significantly fewer remission deaths (P = .025) but a much higher rate of bone marrow relapse than those in group C or G (P = .002). There was an overall benefit for 3 years of chemotherapy compared with 2 years, which in contrast to previous studies, was more apparent in girls and in patients in groups C and G. Testicular relapse occurred in 37 boys, including 19 patients off therapy, with a previously negative biopsy. The overall results confirmed the prognostic significance of initial leucocyte count, even among these standard-risk patients, while girls had a superior rate of disease-free survival, but not of hematologic remission. It is concluded that, even among standard-risk patients, the prognosis is influenced by the height of the initial leukocyte count. While alterations in the fractionation of cranial irradiation do not appear to have influenced disease-free survival, intermittent continuing chemotherapy, although less immunosuppressive, is less effective than conventional continuous therapy in the treatment of ALL. In this study, 3 years of chemotherapy appeared superior to 2 years.

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Child; Child, Preschool; Clinical Trials as Topic; England; Humans; Infant; Leukemia, Lymphoid; Mercaptopurine; Methotrexate; Prednisone; Random Allocation; Vincristine

437 children with acute lymphoblastic leukaemia (ALL) have been treated at 9 different institutions in Austria utilizing common protocols and central registration between 1974 and 1984. 227 patients (132 boys and 95 girls, group I) were treated between 1974 and 1980 using 3 consecutive protocols (KMK, O 76, A 78), which were essentially derived from the Memphis studies VII and VIII. Patients with a high risk of relapse were treated according to the LSA 2-L2 protocol. 210 patients (112 boys and 98 girls, group II) were consecutively treated following the BFM protocols 76/79 and 81/83. In this group, treatment intensity was adjusted to the initially determined individual risk of relapse (BFM risk score or risk factor). To date, the life table analysis demonstrates that the probability of continuous complete remission for patients in group II is 60% after 5 and 3 years (BFM 76/79 and BFM 81/83, respectively), whereas group I reaches a level of 37.3%. The prognostic difference between risk and non-risk patients in both studies of group II was eliminated. Despite a higher morbidity and non-leukaemia-related mortality in group II, the therapeutic success can be attributed to the intensification of induction therapy.

Topics: Asparaginase; Austria; Child; Child, Preschool; Clinical Trials as Topic; Cyclophosphamide; Cytarabine; Daunorubicin; Female; Humans; Infant; Leukemia, Lymphoid; Male; Mercaptopurine; Methotrexate; Neoplasm Recurrence, Local; Prednisone; Risk; Vincristine

108 children with standard-risk acute lymphocytic leukaemia (ALL) were randomised to a post-induction treatment protocol including 15 doses of intermediate-dose methotrexate (1000 mg/m2) in addition to conventional oral therapy of mercaptopurine and low-dose methotrexate. After median follow-up of 26 months, 22 patients have had relapses. Among the 108 patients, rates of methotrexate systemic clearance ranged from 44.7 to 132 ml/min/m2. When the group was divided into three subgroups according to the patients' rates of methotrexate clearance, statistical analysis of the Kaplan-Meier curves estimating the probability of complete remission showed significant differences (p = 0.016) among the subgroups, patients with faster clearance having higher probability of relapse. Multivariate Cox's regression analysis incorporating other potential prognostic variables identified three significant variables influencing the risk of relapse--methotrexate clearance and white-blood-cell count and haemoglobin level at diagnosis (p = 0.0015). This study has demonstrated the potential clinical importance of the rate of drug clearance in children with ALL.

Topics: Bone Marrow Examination; Central Nervous System Diseases; Child; Clinical Trials as Topic; Drug Therapy, Combination; Female; Humans; Kinetics; Leukemia, Lymphoid; Male; Mercaptopurine; Methotrexate; Probability; Random Allocation; Recurrence; Testicular Neoplasms

Topics: Antineoplastic Combined Chemotherapy Protocols; Child; Clinical Trials as Topic; Drug Administration Schedule; Female; Humans; Leukemia, Lymphoid; Male; Mercaptopurine; Methotrexate; Prednisolone; Random Allocation; Vincristine

Topics: Age Factors; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Bone Marrow; Brain Neoplasms; Central Nervous System Diseases; Child; Child, Preschool; Clinical Trials as Topic; Drug Therapy, Combination; Female; Humans; Infant; Leukemia, Lymphoid; Leukocyte Count; Male; Mercaptopurine; Methotrexate; Prednisone; Probability; Prognosis; Random Allocation; Testicular Neoplasms; Vincristine

Two hundred and seventeen patients, 1-50 yr old, with acute lymphoblastic leukemia in complete remission were randomized to receive a 1-yr consolidation chemotherapy of either type P, comprising 7 different drugs, or type M, consisting of methotrexate interspersed with prednisone and vincristine. Thereafter, they were randomized a second time to receive a 4-yr maintenance of either chemotherapy or immunotherapy, comprised of allogeneic blasts and bacillus Calmette-Guérin (BCG). Consolidation P caused more toxicity than consolidation M. However, comparison between the consolidation therapies P and M showed no significant difference, neither for disease-free interval nor for duration of survival. Chemotherapy showed more lethal toxicity in adults than in children. Comparison between chemotherapy (C) and immunotherapy (I) as maintenance treatment showed a significant (p = 0.016) superiority of C for disease-free interval (DFI). The difference was even more pronounced (p = 0.009) in the group with less than 8 g/dl of hemoglobin (Hb) at diagnosis before therapy. On the other hand, for patients with more than 8 g/dl Hb at diagnosis, presumably those with T-ALL, no difference in DFI was seen. No difference has been seen so far between maintenance therapies I and C concerning the duration of survival. The patients who were receiving maintenance I when they relapsed and who were consequently retreated by chemotherapy, survived longer from relapse than those patients retreated for relapse while receiving maintenance C.

Topics: Adolescent; Adult; Asparaginase; BCG Vaccine; Carmustine; Child; Child, Preschool; Cyclophosphamide; Humans; Immunotherapy; Infant; Injections, Spinal; Leukemia, Lymphoid; Lymphocyte Transfusion; Mercaptopurine; Methotrexate; Middle Aged; Prednisone; Vincristine

In a comparison of treatments for standard-risk acute lymphoblastic leukaemia in children (UKALL III), there were no differences in remission lengths between regimens with or without second-line drugs (cytosine arabinoside and asparaginase) and with continuous or discontinuous mercaptopurine. The number of infections was significantly lower when maintenance followed the less immunosuppressive modified induction period and when there were 1-week gaps each month in the administration of mercaptopurine. As in the previous trial, a higher rate of relapse in boys was found to be due partly to testicular and partly to bone marrow relapse. Cell-typing by the FAB system showed that the proportion of patients still in their first remission at 5 years was very much higher in L1 than in L2 cases.

Topics: Adolescent; Antineoplastic Agents; Asparaginase; Bone Marrow Diseases; Child; Child, Preschool; Clinical Trials as Topic; Cytarabine; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Infant; Leukemia, Lymphoid; Male; Mercaptopurine; Neoplasm Recurrence, Local; Prognosis; Sex Factors; Testicular Neoplasms; Time Factors

Topics: Adolescent; Adult; Aged; Clinical Trials as Topic; Cytarabine; Daunorubicin; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Leukemia, Lymphoid; Male; Mercaptopurine; Methotrexate; Middle Aged; Prednisone; Vincristine

Topics: Adjuvants, Immunologic; Blood Proteins; Child; Child, Preschool; Clinical Trials as Topic; Complement System Proteins; Cyclophosphamide; Drug Therapy, Combination; Humans; Immunoglobulins; Leukemia, Lymphoid; Mercaptopurine; Methotrexate; Propionibacterium acnes; Time Factors

Topics: Adolescent; Asparaginase; Child; Child, Preschool; Cyclophosphamide; Cytarabine; Doxorubicin; Female; Humans; Infant; Leukemia, Lymphoid; Male; Mercaptopurine; Methotrexate; Prednisone; Vincristine

Topics: Adolescent; Child; Child, Preschool; Female; Humans; Infant; Leukemia, Lymphoid; Male; Mercaptopurine; Prednisone; Prognosis; Recurrence; Risk; Time Factors; Vincristine

From 1976 until 1978, 136 adult patients with acute leukemia were treated in four hospitals in Berlin. A complete remission was achieved in 47 patients (35%). Twenty-six patients with non-lymphocytic acute leukemia, who had achieved a complete remission with induction chemotherapy consisting of daunorubicin (45 mg/m2/day, day 1, 2 and 3) and cytosine-arabinoside (100 mg/m2/day, continuous infusion, day 1 to day 7) were entered into a randomized trial. Thirteen patients were treated with an intermittent combination chemotherapy at 4-week intervals; the other group of patients received in addition a specific immunotherapy consisting of neuraminidase-modified allogeneic blast cells. The results revealed that the addition of this kind of immunotherapy did not increase the duration of first remission or survival.

Topics: Adolescent; Adult; Cyclophosphamide; Cytarabine; Daunorubicin; Female; Humans; Immunotherapy; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Methotrexate; Middle Aged; Thioguanine; Vincristine

The study was designed to compare the relapse rate and toxicity of intermittent prednisone, oncovin (vincristine), methotrexate, and 6-mercaptopurine (POMP) vs. 6-mercaptopurine daily and a prednisone pulse every three months (PIP) for maintenance therapy in acute leukemia. Children with acute lymphoblastic, acute undifferentiated, or acute stem-cell leukemia were stratified on the basis of initial leukocyte count and age, then randomly assigned to POMP or PIP maintenance therapy. All patients received cranial irradiation and intrathecal chemotherapy. Of the 67 patients receiving POMP maintenance, 20(30%) remain in continuous remission. The median length of continuous remission achieved with POMP therapy was 49 weeks. Of 80 patients receiving PIP maintenance, 25(31%) remain in remission. The median length of continuous remission for PIP was 62 weeks. Of the possible prognostic factors evaluated, the only significant factor was the prognostic grouping base in age and initial leukocyte regimen was associated with a higher incidence of toxic reactions, frequently causing therapy interruption. The results for both regimens as studied are inferior to those for 6-mercaptopurine methotrexate maintenance regimens as reported by others.

Topics: Age Factors; Antineoplastic Agents; Clinical Trials as Topic; Drug Therapy, Combination; Humans; Leukemia, Lymphoid; Leukocyte Count; Mercaptopurine; Methotrexate; Prednisone; Probability; Prognosis; Vincristine

L-Asparaginase, in the dose of greater than or equal to 6000 IU/sq m three times weekly, was demonstrated to be an effective agent in reinduction of remissions in childhood leukemia. Four hundred thirteen children with acute lymphocytic leukemia were treated with L-asparaginase. Doses i.m. ranged from 300 to 12,000 IU/sq m. None of the patients had received prior asparaginase therapy. 6-Mercaptopurine was given p.o. concurrently. All of the patients had experienced several previous relapses, and their disease was not responsive to 6-mercaptopurine. L-Asparaginase was found to be effective in reinducing remissions at the following rates: 9.5% for 300 IU/sq m; 35.1% for 3,000 IU/sq m; 53.5% for 6,000 IU/sq m; and 62.5% for 12,000 IU/sq m. The drug was given three times weekly for four weeks. Hypersensitivity reactions occurred in 6.5% of patients.

Topics: Asparaginase; Child; Child, Preschool; Clinical Trials as Topic; Drug Administration Schedule; Drug Hypersensitivity; Drug Therapy, Combination; Humans; Leukemia, Lymphoid; Mercaptopurine; Neutropenia; Remission, Spontaneous

Topics: Adolescent; Adult; Aged; Clinical Trials as Topic; Cytarabine; Daunorubicin; Drug Therapy, Combination; Female; Humans; Leukemia; Leukemia, Erythroblastic, Acute; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Middle Aged; Prednisolone

This cooperative prospective study was designed to answer the following questions in cases with acute lymphoblastic leukemia induced to achieve complete remission with the combination of vincristine and prednisone (if by day 29 the bone marrow was not M1, daunorubicin was added to the former regimen) and who received preventive CNS therapy with 2400 rad of cobalt-60 to craniocervical region and simultaneously intrathecal methotrexate and dexamethasone: 1) Is a short intensification with cytosine-arabinoside and cyclophosphamide immediately after complete remission useful? 2) Does the use of weekly doses of 6-mercaptopurine and methotrexate have the same maintenance effect as daily 6-mercaptopurine and twice weekly methotrexate? and 3) Do further 3 month-doses of intrathecal methotrexate and dexamethasone help to decrease still more the incidence of meningeal leukemia? From October 1972 to December 1975, 473 previously untreated patients entered this study and 465 (390 children and 75 adults) are evaluated in this paper. Of them, 373 (80%) achieved complete remission (children 84% and adults 61%). Out of 109 "high risk" children (one or more of the following characteristics at diagnosis: marked organomegaly, mediastinal widening, leukocytosis above 50000/mm3 and CNS involvement) 83 (76%) and out of 281 "standard risk" children (all the others) 244 (87%) achieved complete remission. The median duration of complete remission according to different prognostic factors was as follows: "high risk" children 10 months, adults 24 months and "standard risk" children 25 months. Duration of complete remission of the "standard risk" children in relation to with or without intensification, daily or weekly maintenance and additional intrathecal therapy or none, showed no significant difference; however, those who received intensification, daily maintenance and further intrathecal therapy behaved slightly better. Median survival for all the cases of this study was as follows: adults 10 months, "high risk" children 12 months and "standard risk" children 26 months. At 36 months, 13% of "high risk" children, 25% of adults and 39% of "standard risk" children are still alive. We conclude that the variables studied in this protocol did not show significant extension of complete remission, however the sum of them seems to offer some advantage. Moreover, what appears clear is the importance of prognostic factors which must be taken into account in future studies.

Topics: Adolescent; Adult; Aged; Antineoplastic Agents; Central Nervous System Diseases; Child; Cyclophosphamide; Cytarabine; Daunorubicin; Dexamethasone; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Leukemia, Lymphoid; Male; Mercaptopurine; Methotrexate; Middle Aged; Prednisone; Prognosis; Radiotherapy, High-Energy; Remission, Spontaneous; Risk; Time Factors; Vincristine

Gonadal and other types of leukemic "sanctuaries" are probably the main causes of hematological relapse in the treatment of acute leukemia. The introduction of high-dose Methotrexate (HDM) in a consolidation phase is based on theoretical considerations and the use of HDM in malignant tumors. Three courses of Methotrexate, 500 mg/sq.m. at 3-weekly intervals, has been used as part of a consolidation therapy in Norway during the last two years to 59 children with ALL and one with AML. One child died following HDM. Postmortem examination showed that she was not in complete remission at the time. Among 154 courses of HDM in the 60 patients were eight severe reactions, including six cases of allergic-toxic skin reactions. Two patients developed a Stevens-Johnson's like syndrome. Stomatitis was common in those with toxic reactions. The risk of HDM in patients who are not in complete remission is stressed and the use of rescue therapy with two doses of Leukovorin instead of one is recommended. Forty of forty-two children in 1st complete remission have been in sustained primary remission for 4 to 28 months. Two of these 40 children died after about a year from infections. Only two patients so far have relapsed.

Topics: Asparaginase; Child; Clinical Trials as Topic; Dexamethasone; Drug Eruptions; Drug Evaluation; Drug Therapy, Combination; Female; Humans; Infant; Leucovorin; Leukemia, Lymphoid; Mercaptopurine; Methotrexate; Stevens-Johnson Syndrome; Stomatitis; Vincristine

Protocol 7401 for the treatment of acute lymphoblastic leukemia was carried out by the study group of the Italian Association Against Leukemias. The 157 patients studied were divided into two groups--over and under 20 years of age. Patients reaching complete remission were then randomized into one of the two maintenance chemotherapy regimens (A or B). Complete remission was attained in 92.3% of 117 evaluated patients. Ninety-five patients aged under 20 years entered the maintenance regimen; 60% were in complete remission after three years. Computer processing and multiple regression analysis have shown that age, lymph node involvement and the percentage of periodic acid-Schiff-positive blast cells may have prognostic value. However, with the Logrank test it was possible to compare the two maintenance regimens in each group for each prognostic factor. Patients aged between 2 and 10 years responded better to regimen A than to regimen B, as did patients with mild lymph node enlargement. Since some of the host-related factors studied emerged as significant for remission duration, three new protocols taking these prognostic factors into account were started. After one year, actuarial curves showed that 91% of 80 patients in Protocol 7601, 70% of 32 patients in Protocol 7602, and 82% of 33 patients in Protocol 7603 were in complete remission.

Topics: Adolescent; Adult; Asparaginase; Child; Child, Preschool; Cyclophosphamide; Cytarabine; Doxorubicin; Drug Therapy, Combination; Evaluation Studies as Topic; Humans; Leukemia, Lymphoid; Mercaptopurine; Methotrexate; Prednisone; Vincristine

Thirteen adults with acute lymphoblastic leukemia were entered into a protocol in which cytosine arabinoside infusion was added to vincristine and prednisone as remission induction and periodic intensification therapy. Central nervous system prophylaxis consisting of cranial irradiation and intrathecal methotrexate was given, and all patients received continuous oral 6-mercaptopurine and methotrexate as maintenance treatment. Myelotoxicity was severe during induction, with prolonged granulocyte and platelet count nadirs noted. Nine of 13 patients (69%) obtained a complete remission and one (8%) obtained a partial remission. The median duration of complete remission was 38.1 weeks. It was concluded that cytosine arabinoside in combination with vincristine and prednisone is an effective but toxic antileukemic regimen which did not produce a major improvement in remission duration.

Topics: Adult; Aged; Central Nervous System Diseases; Clinical Trials as Topic; Cytarabine; Drug Evaluation; Drug Therapy, Combination; Female; Humans; Leukemia, Lymphoid; Male; Mercaptopurine; Middle Aged; Prednisone; Remission, Spontaneous; Vincristine

Topics: Adolescent; Antineoplastic Agents; Asparaginase; BCG Vaccine; Child; Child, Preschool; Clinical Trials as Topic; Cyclophosphamide; Humans; Immunotherapy; Infant; Leukemia, Lymphoid; Mercaptopurine; Methotrexate; Prednisone; Prognosis; Remission, Spontaneous; Vincristine

The results of treatment in a group of 50 children with acute lymphatic leukemia are summarized. A comparison was made between those who received prophylactic central nervous systen (CNS) therapy on attaining complete remission and those who did not. Although none of the prophylactically treated children developed CNS leukemia, the expected prolongation of median complete remission time was not achieved. It was found that there was a high percentage of poor-risk patients in the CNS-treated group, and these patients relapsed early in the course of the disease. The prevention of CNS leukemia, a late complication of the disease, did not change the natural course of the disease in poor-risk patients. A need exists for new treatment protocols aimed at better control of the disease in these poor-risk cases.

Topics: Adolescent; Central Nervous System Diseases; Child; Child, Preschool; Clinical Trials as Topic; Drug Therapy, Combination; Humans; Infant; Leukemia, Lymphoid; Mercaptopurine; Prednisone; Remission, Spontaneous; Risk; Time Factors

The first and second Medical Research Council UKALL trials have shown that alteration in the timing of methotrexate and 6-mercaptopurine maintenance therapy for the treatment of acute lymphoblastic leukaemia can markedly change drug induced toxicity. Maintenance chemotherapy in both trials used a similar total dosage of these drugs but the timing of their administration was different in the two schedules.

Topics: Child; Child, Preschool; Drug Therapy, Combination; Humans; Infant; Infant, Newborn; Leukemia, Lymphoid; Leukocyte Count; Lymphocytes; Lymphopenia; Mercaptopurine; Methotrexate; Neutropenia; Neutrophils; Remission, Spontaneous; Time Factors

Topics: Acute Disease; Age Factors; Animals; Antineoplastic Agents; Asparaginase; Central Nervous System Diseases; Child; Child, Preschool; Cytarabine; Daunorubicin; Drug Therapy, Combination; Humans; Infant; Leukemia, Lymphoid; Mercaptopurine; Methotrexate; Prednisone; Remission, Spontaneous; Vincristine

The progressive improvement in the prognosis of acute lymphocytic leukemia has been a result of two major developments: 1) the more efficient use of chemotherapeutic agents, particularly the use of combinations of agents and the discovery that agents effective at one stage of disease may be inappropriate at another stage, and 2) the prevention with irradiation of central nervous system relapse. As many as one-half of children with this disease may enjoy long-term leukemia-free survival. However, further studies are needed to improve the efficacy and reduce the toxicity of therapy. This paper reviews the evolution of some of these studies.

Topics: Age Factors; Antineoplastic Agents; Asparaginase; Brain Neoplasms; Child; Child, Preschool; Cyclophosphamide; Cytarabine; Daunorubicin; Drug Therapy, Combination; Female; Humans; Leukemia, Lymphoid; Male; Mercaptopurine; Methotrexate; Prednisone; Radiotherapy; Remission, Spontaneous; Spinal Cord Neoplasms; Vincristine

One hundred and forty-nine children with acute lymphocytic leukemia treated according to a prospective protocol were randomized after induction of remission and central nervous system (CNS) irradiation to receive maintenance chemotherapy with 1, 2, 3, or 4 chemotherapy agents. The incidence of P. carinii pneumonitis (PCP) was 5.0, 2.3, 2.2, and 22.4%, respectively, during the period of maintenance therapy. An additional 31 patients enrolled in the same study were placed in special categories to receive three drugs for maintenance plus supplemental chemotherapy or irradiation because of CNS leukemia on admission, remission failure, ediastinal mass, or generalized lymphosarcoma without bone marrow involvement. The incidences of PCP in these groups were 16.7, 30.0, 35.7, and 0%, respectively, during the period of maintenance therapy.

Topics: Antineoplastic Agents; Asparaginase; Child, Preschool; Cyclophosphamide; Cytarabine; Drug Therapy, Combination; Female; Humans; Immunosuppression Therapy; Leukemia, Lymphoid; Male; Mercaptopurine; Methotrexate; Pneumonia, Pneumocystis; Prednisone; Vincristine

The degree of drug-induced neutropenia resulting from a controlled trial (UKALL I) of treatment in acute lymphoblastic leukaemia was analysed. The main agent associated with severe neutropenia was methotrexate, and methotrexate-induced neutropenia was significantly greater in patients who had received craniospinal irradiation. The synergistic toxic effect of irradiation followed by methotrexate treatment seems to have contributed to three of the five deaths which occurred in complete remission in this trial; all deaths in remission occurred in patients who had received central nervous system prophylaxis. Analysis of patients who subsequently relapsed compared with those still in remission after 18 months of treatment indicated that the former, on average, had slightly lower neutrophil counts. This suggests that the children who relapsed did not receive any less aggressive treatment than those who remained in remission.

Topics: Agranulocytosis; Central Nervous System; Child; Child, Preschool; Clinical Trials as Topic; Cytarabine; Dose-Response Relationship, Drug; Drug Therapy, Combination; Humans; Injections, Spinal; Leukemia, Lymphoid; Lymphocytes; Mercaptopurine; Methotrexate; Neutropenia; Prednisolone; Radiation Effects; Radiotherapy Dosage; Remission, Spontaneous; Time Factors; Vincristine

Topics: Administration, Oral; Adult; Cyclophosphamide; Cytarabine; Daunorubicin; Drug Therapy, Combination; Female; Humans; Injections, Intravenous; Leukemia, Lymphoid; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Methotrexate; Middle Aged; Prednisone; Prognosis

Topics: Adolescent; Asparaginase; Child; Child, Preschool; Clinical Trials as Topic; Cytarabine; Drug Therapy, Combination; Humans; Infant; Leukemia, Lymphoid; Male; Mercaptopurine; Methotrexate; Posture; Prednisolone; Radiotherapy Dosage; Vincristine

Topics: Adolescent; Central Nervous System; Central Nervous System Diseases; Child; Child, Preschool; Cobalt Isotopes; Cyclophosphamide; Humans; Injections, Spinal; Leukemia, Lymphoid; Leukocyte Count; Mercaptopurine; Methotrexate; Prednisone; Recurrence; Vincristine

Topics: Adolescent; Adult; Blood Transfusion, Autologous; Brain Neoplasms; Child; Child, Preschool; Cobalt Isotopes; Cyclophosphamide; Female; Humans; Infant; Infections; Injections, Intravenous; Leukemia, Lymphoid; Male; Mercaptopurine; Methotrexate; Radiation Dosage; Radiation Effects; Remission, Spontaneous; Spinal Cord Neoplasms; Time Factors

Topics: Adult; Canada; Child; Denmark; France; Humans; Leukemia, Lymphoid; Mercaptopurine; Methotrexate; Prednisone; Prognosis; South Africa; Switzerland; United States; Vincristine

Topics: Adolescent; Adult; Antineoplastic Agents; Asparaginase; Carmustine; Cell Division; Cell Transformation, Neoplastic; Child; Child, Preschool; Daunorubicin; Humans; Infant; Infant, Newborn; Leukemia, Lymphoid; Mercaptopurine; Methotrexate; Mitosis; Prednisone; Remission, Spontaneous; Vincristine

One hundred and ninety-one cases of acute lymphoblastic leukaemia were entered in a trial in which, for five months, all received cytotoxic therapy with prednisolone, vincristine, mercaptopurine, L-asparaginase, and methotrexate (the latter in high dosage followed by folinic acid). Patients were then randomized to receive immunotherapy (B.C.G.), twice-weekly methotrexate, or no further treatment.One hundred and seventy-seven patients (93%) achieved full remission and at the time of analysis, 26 months from the beginning of the trial, 143 were still alive, including 70 in their first remission. Median "post-intensive" remission lengths were 17 weeks (no treatment), 27 weeks (B.C.G.), and 52 weeks (methotrexate). The prolongation of remission by methotrexate was most evident in those patients with low initial white cell counts. B.C.G. seemed to cause lymphocytosis but was without other conspicuous effect. The incidence of toxic reactions is reported, including an unusually low rate of anaphylaxis with L-asparaginase.These preliminary results are discussed and compared with those of similar trials.

Topics: Acute Disease; Adolescent; Adult; Anaphylaxis; Asparaginase; BCG Vaccine; Child; Child, Preschool; Clinical Trials as Topic; Humans; Infant; Leucovorin; Leukemia, Lymphoid; Leukocyte Count; Lymphocytes; Lymphocytosis; Mercaptopurine; Methotrexate; Prednisolone; Remission, Spontaneous; Skin Tests; Tuberculin Test; Vincristine

Topics: Animals; Antibiotics, Antineoplastic; Antineoplastic Agents; Asparaginase; Azaserine; Cell Division; Clinical Trials as Topic; Cyclophosphamide; Cytarabine; Disease Models, Animal; Drug Combinations; Humans; Kinetics; Leukemia L1210; Leukemia, Experimental; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Mercaptopurine; Methotrexate; Neoplasms; Prednisone; Remission, Spontaneous; RNA, Neoplasm; Vincristine

Topics: Adult; Antineoplastic Agents; Asparaginase; Child; Clinical Trials as Topic; Cyclophosphamide; Cytarabine; Daunorubicin; Humans; Leukemia, Lymphoid; Mercaptopurine; Methotrexate; Prednisolone; Prednisone; Remission, Spontaneous; Vinblastine; Vincristine

Topics: Adolescent; Antibiotics, Antineoplastic; Child; Child, Preschool; Clinical Trials as Topic; Colonic Neoplasms; Cyclophosphamide; Drug Combinations; Evaluation Studies as Topic; Female; Fluorouracil; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Methotrexate; Prednisone; Remission, Spontaneous; Vincristine

Active non-specific immunotherapy has been used to prolong remissions in acute lymphoblastic leukaemia. The series reported here used Bordetella pertussis vaccine in a controlle trial after intensive chemotherapy. Possibly immunotherapy delayed the onset of relapse in the treated patients, but no long-term remissions were obtained. Further work is needed to establish the role of immunotherapy in general, and the use of B. pertussis vaccine in particular, in the treatment of acute leukaemia.

Topics: Acute Disease; Clinical Trials as Topic; Female; Humans; Immunotherapy; Leukemia, Lymphoid; Male; Mercaptopurine; Pertussis Vaccine; Prednisolone; Vincristine

Topics: Adult; Azathioprine; Child; Child, Preschool; Clinical Trials as Topic; Female; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Lung Diseases; Male; Mercaptopurine; Radiography, Thoracic; Vincristine

Topics: Adolescent; Adult; Drug Synergism; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Mercaptopurine; Methotrexate; Prednisone

Topics: Adolescent; Adult; Aged; Blood; Clinical Trials as Topic; Humans; In Vitro Techniques; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Mercaptopurine; Middle Aged; Prednisone; Prognosis; Statistics as Topic

Topics: Adolescent; Child; Child, Preschool; Humans; Infant; Leukemia; Leukemia, Lymphoid; Mercaptopurine; Methotrexate; Prednisone

Topics: Adolescent; Adult; Bone Marrow Cells; Child; Child, Preschool; Clinical Trials as Topic; Drug Synergism; Humans; Leukemia, Lymphoid; Leukocyte Count; Mercaptopurine; Methotrexate; Prednisone

Topics: Adolescent; Adult; Child; Child, Preschool; Female; Genetic Variation; Humans; Infant; Leukemia, Lymphoid; Male; Mercaptopurine; Pyrophosphatases; Young Adult

The effects of prolonged exposure to 2 and 10 microM 6-mercaptopurine (6MP) in the human lymphoblastic T-cell line MOLT-4 were studied with respect to cell-kinetic parameters, phosphoribosyl pyrophosphate (PRPP) and purine ribonucleotide levels, formation of 6MP-nucleotides, especially methyl-thio-IMP (Me-tIMP), DNA and RNA synthesis ([32P] incorporation), and [8-14C]6MP incorporation into newly synthesized DNA and RNA. The results provided new insights into the complex mechanism of action of 6MP in human malignant lymphoblasts. Exposure to 2 microM 6MP resulted in a rapid inhibition of purine de novo synthesis (PDNS) by increased levels of Me-tIMP, resulting in increased PRPP levels and decreased purine ribonucleotides, affecting cell growth and clonal growth, and less cell death. DNA synthesis decreased, associated with an increasing delay of cells in S phase. Incorporation of thioguanine nucleotides into newly synthesized DNA resulted in an increasing arrest of cells in G2 + M phase. RNA synthesis, initially decreased, recovered partially, associated with a recovery of purine ribonucleotides. New formation of 6MP-nucleotides (tIMP) was only detected within the first 24 hr, and 6MP levels in the culture medium were already undetectable after 6 hr of exposure to 2 microM, indicating a high rate of incorporation and complete conversion of 6MP within this period. Incorporation of 6MP-nucleotides into DNA was 5 times as high as incorporation into RNA. Exposure to 10 microM 6MP resulted in early cytotoxicity at 24 hr, associated with a complete inhibition of PDNS by a large pool of Me-tIMP and lower levels of purine ribonucleotides as compared to 2 microM 6MP. A more severe delay of cells in S phase was associated with an inhibition of DNA synthesis to 14% of control within the first 24 hr, and an arrest in G2 + M phase. Further increasing levels of Me-tIMP caused an arrest of cells and late cytotoxicity in S phase at 48 hr, preventing further progression into G2 + M phase. Our data suggest that inhibition of PDNS due to Me-tIMP is a crucial event in the mechanism of 6MP cytotoxicity. It is responsible for decreased RNA synthesis and decreased availability of natural deoxyribonucleotides, causing a delay of DNA synthesis in S phase. This enhances incorporation of 6MP as thioguanine nucleotides into DNA in the S phase and subsequent late cytotoxicity in the G2 phase. However, with high concentrations of 6MP, the large pool of Me-tIMP causes severe reduction o

Topics: Carbon Radioisotopes; Cell Cycle; DNA; Humans; Inosine Monophosphate; Leukemia, Lymphoid; Mercaptopurine; Phosphoribosyl Pyrophosphate; Phosphorus Radioisotopes; Ribonucleotides; RNA; Stem Cells; T-Lymphocytes; Thionucleotides

Methotrexate (MTX) accumulates in erythrocytes (ery) during weekly MTX administration, and the ery-MTX concentration reaches a steady state after 4-6 weeks. In order to study MTX accumulation and metabolism to polyglutamate derivatives in different age populations of red blood cells, we took erythrocytes from 12 children with ALL who were receiving maintenance treatment with MTX and 6-MP and separated them according to age on a discontinuous Percoll gradient. When the erythrocytes of these children were separated according to specific gravity a normal distribution was obtained. Age fractionation was confirmed by the exponential decline of the erythrocyte aspartate aminotransferase (ery-ASAT) and by the reticulocyte counts. The ery-MTX declined with increasing red blood cell age in an exponential manner no different from the decline of the ery-ASAT. The youngest population of red blood cells contained 2.3-5.9 (mean 3.8) times more MTX than the oldest population. By linear regression analysis the t1/2 of the ery-MTX was 19-79 days (mean 37 days). The ery-MTX t1/2 seemed to be directly related to the amount of MTX which had been metabolized to MTX-glu3-5. The decline of the ery-MTX was predominantly due to selective disappearance of MTX-glu1+2, whereas MTX-glu3-5 changed to a much lesser extent with advancing red blood cell age. The present investigation showed that steady-state ery-MTX concentration was determined by (1) the amount of MTX added to the circulation by the reticulocytes, (2) the in vivo loss predominantly of MTX with low numbers of glutamyl derivatives from erythrocytes, and (3) the loss of MTX from destroyed red blood cells. The observed in vivo disappearance of MTX from erythrocytes offers a possible explanation of the observation that the ery-MTX steady state was reached after 4-6 weeks of unaltered weekly MTX treatment.

Topics: Antineoplastic Combined Chemotherapy Protocols; Child; Erythrocyte Aging; Erythrocyte Count; Erythrocytes; Humans; Leukemia, Lymphoid; Mathematics; Mercaptopurine; Methotrexate; Peptides; Polyglutamic Acid; Regression Analysis; Reticulocytes

Methotrexate and methotrexate polyglutamates were quantitatively determined in red blood cells from 12 children with acute lymphoblastic leukemia who were treated with MTX (15-20 mg/m2 per week) and daily 6-mercaptopurine orally during the steady-state period of erythrocyte MTX concentration (ery-MTX). The terminal decline of the ery-MTX and its polyglutamate metabolites were determined for up to 15 weeks after cessation of MTX treatment. Methotrexate polyglutamates with 2-4 extra glutamyl derivatives (MTX-glu2-5) constituted 75% of the MTX in the entire red blood cell population. MTX-glu3 was the principal metabolite; no MTX-glu6-7 was identified. After discontinuation of MTX therapy, the ery-MTX declined in a non-linear manner because of different half-lives for the individual polyglutamates. From about 5 weeks until 13-15 weeks after the last MTX dose, the erythrocyte MTX elimination curve was linear. The approximate half-life of MTX-glu1 was 2-3 days; for MTX-glu2 it was 4-15 days. The concentration of MTX-glu3-5 remained constant in the erythrocyte throughout its life span and declined only with age-dependent destruction of the red blood cell. It was calculated that 80%-90% of MTX in newly formed reticulocytes was MTX-glu1+2, the remainder being MTX-glu3-5. Mature red blood cells did not form methotrexate polyglutamates to any significant degree. There was a significant correlation between the amount of MTX-glu3-5 and the steady -state ery-MTX, which to some extent explained the interindividual variation of the ery-MTX in children with ALL in maintenance therapy.

Topics: Administration, Oral; Antineoplastic Combined Chemotherapy Protocols; Child; Erythrocyte Aging; Erythrocytes; Humans; Leukemia, Lymphoid; Mercaptopurine; Methotrexate; Peptides; Polyglutamic Acid

A 6-year-old boy on maintenance chemotherapy for acute lymphocytic leukemia developed severe hypoplastic anemia during chemotherapy previously well tolerated. The hypoplastic episode persisted for approximately 30 days. Human parvovirus (B19), the etiologic agent of aplastic crisis in persons with underlying hemolytic syndromes, was detected in the patient's serum 25-30 days after onset of hemoglobin decrease, and B19 IgM seroconversion occurred 1 week later. The patient's hypoplastic anemia was presumably caused by prolonged B19 infection resulting from a blunted immune response. An immune response to the B19 infection and resolution of the illness were temporally associated with brief cessation of chemotherapy.

Topics: Anemia, Aplastic; Antineoplastic Agents; Child; Humans; Leukemia, Lymphoid; Male; Mercaptopurine; Methotrexate; Parvoviridae Infections; Prednisone; Vincristine

We studied the prescription patterns of maintenance therapy for children with acute lymphoblastic leukemia and their association with duration of complete remission. Both 6-mercaptopurine and methotrexate (MTX) were prescribed in doses significantly lower than those recommended (75 mg/m2 daily 6-mercaptopurine; 20 mg/m2 weekly MTX) during maintenance therapy. Of 212 evaluated patients, patients who had relapses (n = 101) received significantly less MTX compared with patients who did not have relapses (n = 111) during the first 2 years of maintenance therapy. In the group of standard-risk patients who received the same induction therapy (n = 92), 11 of 17 who received less than 50% of the recommended MTX dose (64%) and 28 of 75 who received greater than 50% of the dose (37%) had relapses (P less than 0.05). The two groups had comparable periods of interruption of MTX therapy. Further analysis revealed that the lower maintenance dose stemmed from a continuous low prescribed dose and not from more frequent interruption of therapy in relapse. Physicians' inability or failure to adhere to the recommended protocol was associated with a higher relapse rate of acute lymphoblastic leukemia. Improved physicians' compliance may improve the prognosis of the disease.

Topics: Administration, Oral; Brain Neoplasms; Child; Humans; Injections, Spinal; Leukemia, Lymphoid; Mercaptopurine; Methotrexate; Neoplasm Recurrence, Local; Practice Patterns, Physicians'; Radiotherapy Dosage; Remission Induction

Topics: Antineoplastic Combined Chemotherapy Protocols; Child; Epilepsy; Humans; Leukemia, Lymphoid; Male; Mercaptopurine; Metabolic Clearance Rate; Methotrexate; Phenytoin; Prednisone; Vincristine

In three children receiving oral remission maintenance therapy for acute lymphoblastic leukemia, the concentrations of 6-mercaptopurine (6-MP) in cerebrospinal fluid (CSF), plasma and red blood cells were compared. CSF samples were obtained from an Ommaya reservoir previously inserted for treatment of CNS relapse. At the time of the study, the children were all in remission and had been on oral 6-MP (42-63 mg m-2) once daily for at least 24 weeks. Immediately before dose intake on the day of study (about 24 h after last dose), the concentrations of 6-MP in CSF, plasma and red blood cells were rather similar and below 20 ng ml-1 in all patients. After dose intake, the concentrations in plasma and in red blood cells increased to 40-200 ng nl-1 within 0.5-4 h. In contrast, the concentration of 6-MP in the CSF remained fairly constant around 4-10 ng ml-1 throughout the time period studied (up to 4 h). It is concluded that 6-MP can be detected in CSF during oral maintenance therapy and that the drug has different pharmacokinetic profile in CSF to that in plasma and red blood cells. Further studies are necessary to evaluate the significance of the 6-MP concentrations obtained in CSF for the prevention of CNS relapse.

Topics: Administration, Oral; Child; Erythrocytes; Female; Humans; Leukemia, Lymphoid; Male; Meningeal Neoplasms; Mercaptopurine; Remission Induction

Cyclic combination chemotherapy was administered to 26 patients with acute lymphoblastic leukemia who had relapsed in the bone marrow greater than or equal to 6 months after elective cessation of therapy. Each patient had been in initial continuous complete remission for 36-111 months (median, 47 months). Prednisone, vincristine, and doxorubicin induced second complete remissions in all patients within 1 month. Continuation therapy consisted of alternating 6-week courses of 6-mercaptopurine/methotrexate and vincristine/cyclophosphamide with intervening reinforcement courses of prednisone/doxorubicin, for a total of 18 months. All patients received 4 weeks of late intensification therapy with the same agents used for remission reinduction. Periodic intrathecal methotrexate was given as reprophylaxis for subclinical central nervous system leukemia. The estimated rate of continuous failure-free survival at 5 years is 31% +/- 17% (2 SE). Eight patients remain free of leukemia for 42 + to 65+ months after completing therapy a second time. Adverse second events included 11 hematologic, 1 testicular, and 3 meningeal relapses. Patients who relapsed at more than 12 months after the completion of initial treatment have had significantly longer second remissions than patients whose first remissions were shorter (p = .04). None of the other six factors we analyzed showed predictive strength. These end results indicate that intensive cyclic continuation chemotherapy, as described here, will secure durable second remissions in approximately one-third of the children with late bone marrow relapses.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Child; Child, Preschool; Cyclophosphamide; Doxorubicin; Drug Administration Schedule; Female; Humans; Leukemia, Lymphoid; Male; Mercaptopurine; Methotrexate; Prednisone; Time Factors; Vincristine

Hepatocellular carcinoma (HCC) occurred in a 28-year-old woman treated for acute lymphocytic leukemia (ALL) with methotrexate (MTX) and 6-mercaptopurine (6-MP), off all therapy for 15 years, who was also heterozygous for alpha-1 antitrypsin (alpha-1 AT) deficiency. MTXD is responsible for the development of HCC in this patient. The literature concerning the incidence of HCC in patients treated with MTX and 6-MP and in alpha-1 antitrypsin deficiencies is reviewed.

Topics: Adult; alpha 1-Antitrypsin; alpha-Fetoproteins; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Hepatocellular; Female; Humans; Leukemia, Lymphoid; Liver Cirrhosis; Liver Neoplasms; Mercaptopurine; Methotrexate; Neoplasm Proteins; Neoplasms, Multiple Primary

Topics: Child; Humans; Leukemia, Lymphoid; Mercaptopurine; Remission Induction

Topics: 5'-Nucleotidase; Child; Drug Resistance; Humans; Leukemia, Lymphoid; Mercaptopurine; Nucleotidases

Topics: Antiviral Agents; Drug Interactions; Humans; Leukemia, Lymphoid; Mercaptopurine; Nucleosides

Fourteen children (aged 3 to 14 years) with average-risk acute lymphoblastic leukemia were studied after an oral dose of 6-mercaptopurine (6-MP) (75 mg/m2) administered alone and, on the next day, concurrently with oral methotrexate (20 mg/m2). When 6-MP was administered alone, both the peak plasma concentration (15 to 150 ng X ml-1) and the AUC (36 to 340 ng X ml-1 X hr) were highly variable. Concurrent methotrexate resulted in a 31% increase in the AUC (P less than 0.01) and a 26% increase in peak plasma levels (P less than 0.05) of 6-MP. The AUC of methotrexate correlated with the degree of increase in 6-MP plasma concentrations. These findings are consistent with previous in vitro studies demonstrating that methotrexate is an inhibitor of xanthine oxidase, the enzyme that catabolizes 6-MP to the inactive metabolite thiouric acid. Although the increases in 6-MP AUC and peak plasma concentrations resulting from concurrent methotrexate administration were statistically significant, this interaction is probably not clinically significant at standard low oral doses of methotrexate in light of the wide interpatient variability in these pharmacokinetic parameters of 6-MP.

Topics: Administration, Oral; Adolescent; Biological Availability; Child; Child, Preschool; Chromatography, High Pressure Liquid; Drug Interactions; Female; Humans; Kinetics; Leukemia, Lymphoid; Male; Mercaptopurine; Methotrexate

Methotrexate (MTX) and 6-mercaptopurine (6-MP) are used for maintenance therapy of acute lymphoblastic leukemia (ALL) of childhood, and both are myelotoxic. Clinically the individual tolerance to the two drugs is variable. In order to study to what extent the MTX accumulation in circulating neutrophils is related to the absolute neutrophil count (ANC), neutrophils were isolated on a discontinuous two-step Percoll gradient in 16 children with ALL in maintenance therapy. The MTX concentration in the neutrophils was determined with a sensitive radioligand binding assay. In all children except one who admitted noncompliance, MTX was found in the neutrophils in concentrations (56-460 pmol/10(9) cells) positively correlated with the weekly dose of MTX (r = 0.51, p less than 0.01). The interindividual variation was large. Children with relatively low neutrophil MTX exhibited the widest intraindividual variation of neutrophil MTX upon reexamination during continued MTX administration with the same dosage schedule. Increases in the weekly dose of MTX resulted in proportional increases in the neutrophil MTX. In half the cases the ANC was less than 1.5 X 10(9)/l. The ANC was not related to the weekly MTX dose or the daily 6-MP dose. In children with ANC greater than 1.5 X 10(9)/l there was a significant inverse correlation between the ANC and the neutrophil MTX (r = -0.71, P less than 0.01), which was not found in the group of children with ANC less than 1.5 X 10(9)/l. These findings may be explained by differences in the kinetics of the granulopoiesis between children with high and children with low neutrophil counts.

Topics: Antineoplastic Combined Chemotherapy Protocols; Cell Separation; Child; Drug Administration Schedule; Humans; Leukemia, Lymphoid; Leukocyte Count; Mercaptopurine; Methotrexate; Neutropenia; Neutrophils; Statistics as Topic

Childhood acute lymphoblastic leukemia with an initial leukocyte count greater than or equal to 100 X 10(9)/L responds poorly to conventional chemotherapy. To extend event-free survival (EFS) in this disease, we devised a protocol that specifies intensive 2-week courses of teniposide (VM-26, 165 mg/m2) plus cytarabine (ara-C, 300 mg/m2), before and immediately after standard 4-week remission induction therapy with prednisone, vincristine, and L-asparaginase. The VM-26 and ara-C combination was also administered intermittently for the first year of continuation treatment with oral 6-mercaptopurine and methotrexate. CNS prophylaxis consisted of periodic intrathecal (IT) injections of methotrexate and delayed cranial irradiation. At a median follow-up of 4 years, the estimated EFS rate for 57 consecutive patients with leukocyte counts of 100 to 1,000 X 10(9)/L was 44%, compared with 10% for matched controls (P less than .001). Remission induction rates in the two groups were similar (82% v 72%, P = .16). Twenty-five patients in the VM-26/ara-C group have survived without adverse events for 2.7 to 6.8 years, whereas only nine of the controls achieved more than a year of EFS. The most common complications during early treatment were acute hyperkalemia from rapid tumor cell lysis and infections due to prolonged marrow aplasia. Continuation chemotherapy was well tolerated. We conclude that VM-26 plus ara-C, added to each phase of an otherwise basic regimen of chemotherapy, will substantially improve prognosis in this high-risk form of childhood leukemia.

Topics: Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Child; Cytarabine; Drug Administration Schedule; Female; Humans; Leukemia, Lymphoid; Leukocyte Count; Male; Mercaptopurine; Methotrexate; Prednisone; Remission Induction; Teniposide; Vincristine

Sixteen episodes of a distinctive, papular rash occurred in eight patients following withdrawal of 6-mercaptopurine (6MP) and methotrexate (MTX) used as maintenance therapy for acute lymphoblastic leukemia (ALL). The rash also developed in one of the eight patients when only 6MP was discontinued. The eruption occurred mainly on the face, and in this site resembled the perioral dermatitis seen following withdrawal of topical fluorinated steroids. The rash generally began within 3 weeks of stopping 6MP and lasted 3 to 4 weeks. It failed to improve with the use of topical corticosteroid. We conclude that this rash is caused by the withdrawal of oral 6MP.

Topics: Child; Face; Female; Humans; Leukemia, Lymphoid; Male; Mercaptopurine; Skin Diseases; Substance Withdrawal Syndrome

Mercaptopurine (MP) is a purine antimetabolite widely used for remission maintenance in the therapy of acute lymphoblastic leukemia. In order to study the biochemical parameters affecting MP activity, leukemic cells were obtained from ten patients with acute lymphoblastic leukemia at the time of diagnosis and from the same patients at the time of their initial marrow relapse. Hypoxanthine phosphoribosyltransferase (HPRT), the enzyme that converts MP to its active, nucleotide metabolite, thioinosine monophosphate; alkaline phosphatase, the primary catabolic enzyme of thioinosine monophosphate; and 5-phosphoribosyl-1-pyrophosphate (PRPP), the cellular ribose-phosphate donor essential for MP activation, were all measured within the patients' leukemic cells. There was marked interpatient variability in the three biochemical parameters studied with a greater than 10-fold range in alkaline phosphatase activity and an approximately 100-fold range in HPRT activity and PRPP levels. Four patients developed changes in biochemical parameters that influence MP activity at the time of relapse. In three of the four patients, alterations in more than one of these three biochemical parameters were noted. Three of four patients had a greater than 50% decrease in intracellular HPRT activity, four of four had a greater than 50% decrease in intracellular PRPP, and two of four had a greater than 9-fold increase in intracellular alkaline phosphatase activity at relapse. Two of four patients demonstrated changes in all three parameters at relapse in the directions that could have resulted in decreased MP sensitivity (i.e., decreased HPRT, decreased PRPP, and increased alkaline phosphatase). There was no correlation between pretreatment values of HPRT, PRPP, and alkaline phosphatase and remission duration. These results indicate that: (a) there is marked variation in HPRT, PRPP, and alkaline phosphatase in patients with acute lymphoblastic leukemia and b) following MP-containing maintenance chemotherapy, some patients develop biochemical changes that may result in decreased sensitivity to MP.

Topics: Alkaline Phosphatase; Blood Cells; Female; Humans; Hypoxanthine Phosphoribosyltransferase; Leukemia, Lymphoid; Male; Mercaptopurine; Pentosephosphates; Phosphoribosyl Pyrophosphate

Methotrexate (MTX) and 6-mercaptopurine (6MP) are common drugs in the oral maintenance therapy of acute lymphoblastic leukemia (ALL). On the basis of their biochemical effects on cell metabolism, a sequence-dependent synergism might be anticipated. In order to investigate this hypothesis, MOLT-4 human malignant T-lymphoblasts were incubated with various concentrations of MTX. The time at which maximal increase of intracellular 5-phosphoribosyl-1-pyrophosphate (PRPP) levels was found correlated with the concentrations of MTX used. Determination of aminoimidazolecarboxamide ribonucleoside monophosphate (AICAR) levels and labeled glycine incorporation into purine metabolites revealed an incomplete inhibition of purine de novo synthesis after incubation with 0.02 microM MTX, and a complete inhibition with 0.2 microM MTX. After prolonged periods of incubation, glutamine exhaustion of the medium caused inhibition of purine de novo synthesis in MTX-untreated cells, with a concomitant increase of PRPP levels. Addition of glutamine to the medium prevented this phenomenon. The increased availability of PRPP after pretreatment with MTX can be used for enhanced intracellular incorporation of hypoxanthine and 6MP in their respective nucleotides. The time- and dose-dependent effects of MTX on PRPP levels correlated with the enhanced incorporation of hypoxanthine and 6MP. The data presented in this study demonstrate that a synergistic action of the combination of MTX and 6MP can be anticipated in malignant lymphoblasts with an active purine de novo synthesis depending on the concentration of MTX and on the time and sequence of administration of both drugs.

Topics: Aminoimidazole Carboxamide; Cell Line; Drug Synergism; Glutamine; Glycine; Humans; Hypoxanthine; Hypoxanthines; Leukemia, Lymphoid; Mercaptopurine; Methotrexate; Phosphoribosyl Pyrophosphate; Purines; Ribonucleotides; T-Lymphocytes

Topics: Animals; Child; Drug Administration Schedule; Humans; Leukemia, Lymphoid; Mercaptopurine; Methotrexate; Seasons

Topics: Drug Resistance; Humans; Leukemia, Lymphoid; Mercaptopurine

We prospectively assigned 289 consecutive children with acute lymphoblastic leukemia to receive one of two treatment programs on the basis of the presence or absence of certain risk factors at the time of diagnosis. Patients at high risk (62 percent of the total) had one or more of the following risk factors: age below two or above nine years, a white-cell count of 20,000 per cubic millimeter or more, the presence of T-cell immunologic markers, radiologic evidence of a mediastinal mass, and involvement of the central nervous system. Patients in both the standard-risk and high-risk groups were treated for two years, receiving intensive remission-induction therapy, central nervous system prophylaxis, weekly administration of high-dose asparaginase, and multiple-drug continuation therapy (which in the high-risk group included doxorubicin and a larger dose of prednisone). At a median follow-up of 35 months, the mean (+/- SE) event-free survival rates at four years among the patients in the standard-risk and high-risk groups were 86 +/- 4 percent and 71 +/- 4 percent, respectively (P = 0.003), for a total event-free survival of 77 +/- 3 percent. Within the high-risk group, the white-cell count at diagnosis and the sex of the patient were not significant prognostic indicators, but age below 12 months at diagnosis was associated with a very poor outcome. As compared with previous methods, this treatment program using four-drug induction and intensive asparaginase therapy has resulted in improved event-free survival in children with acute lymphoblastic leukemia.

Topics: Adolescent; Age Factors; Antigens, Neoplasm; Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Brain Neoplasms; Child; Child, Preschool; Doxorubicin; Drug Administration Schedule; Female; Humans; Infant; Infant, Newborn; Leukemia, Lymphoid; Leukocyte Count; Male; Mercaptopurine; Methotrexate; Neprilysin; Prednisone; Prognosis; Prospective Studies; Risk; Vincristine

The effect of folic acid supplements on 6-mercaptopurine remission maintenance therapy in lymphoblastic leukaemia (ALL) was investigated in a retrospective longitudinal study of 10 children. Red cell concentrations of 6-thioguanine nucleotide, a cytotoxic metabolite of 6-mercaptopurine, were measured and the peripheral neutrophil count was used as an index of myelosuppression. During the control period of the study there were significant correlations between 6-mercaptopurine dose and 6-thioguanine nucleotide concentration (rs = 0.59, P less than 0.0005) and between 6-thioguanine nucleotide concentration and the peripheral neutrophil count at 14 days (rs = 0.58, P less than 0.0005). These relationships were absent when the same children were subsequently taking folate supplements. Also when taking folate supplements the children tolerated significantly more 6-mercaptopurine (P less than 0.005) for a significantly longer time (P less than 0.005) before neutropenia developed. There was no significant difference in red cell 6-thioguanine nucleotide concentration in the absence and presence of folate supplements. These findings suggest that folate supplements may interfere with remission maintenance therapy in ALL.

Topics: Adolescent; Child; Child, Preschool; Drug Therapy, Combination; Female; Folic Acid; Humans; Leukemia, Lymphoid; Leukocyte Count; Male; Mercaptopurine; Neutropenia; Neutrophils; Thioguanine

Rational treatment of pediatric malignancies requires a detailed knowledge of the clinical pharmacology of those antineoplastic agents used therapeutically. A number of different agents are administered by the oral route. Recently, the clinical pharmacology of 6-mercaptopurine (6-MP) and methotrexate (MTX), the two agents that are the mainstay of maintenance chemotherapy in acute lymphoblastic leukemia (ALL), were investigated. Studies of oral 6-MP indicate that, contrary to previous information, the bioavailability of this drug is relatively poor after oral administration, and that plasma 6-MP concentrations achieved after uniform oral dosing are highly variable. Similarly, study of the pharmacology of orally administered MTX indicates that there is little correlation between MTX dose and the peak serum level achieved. These findings suggest that some patients may not be exposed to adequate systemic concentrations of 6-MP and/or MTX after oral administration, and raise the possibility that the development of relapse in some patients with ALL may be the result of a pharmacologic failure of oral maintenance therapy. A comprehensive prospective study of the clinical pharmacology of MTX and 6-MP in patients with ALL undergoing maintenance chemotherapy is currently in progress.

Topics: Administration, Oral; Allopurinol; Biological Availability; Child; Circadian Rhythm; Drug Administration Schedule; Drug Interactions; Food; Humans; Infusions, Parenteral; Kinetics; Leukemia, Lymphoid; Mercaptopurine; Methotrexate; Recurrence

The relapsing process in the bone marrow was studied in those 77 patients with adult acute leukemia, diagnosed according to the FAB classification who achieved complete remission (CR) and then received intermittent multi-drug intensification treatment. Relapse occurred in most of the patients who exhibited Auer rods or Ph1 chromosomes in the bone marrow, or in whom blasts increased to 8% or more, but some patients remained in CR by subsequent treatment, that is, relapsing process was reversible. With our conventional treatment, the relapse or relapsing process occurred in most of the patients with L1, L2 and M1 subtypes within 6 months and was irreversible. It occurred mainly between 5 and 13 months in those with M2, M3 and M5 and was reversible in some cases. Patients with M4 subtype received intensified treatment due to the difficulty of achieving remission; relapse was seen in only 3 of 7 cases. To prevent relapse and attain a potential cure, the treatment should be intensive before the relapsing process with adequate supporting care. In view of the above-mentioned observations, our new treatment protocols for acute leukemia were designed to be more intensive than those conventionally employed, and to be discontinued within approximately 10 months in lymphoblastic leukemia and approximately 8 months in myeloid leukemia.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Daunorubicin; Humans; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Mercaptopurine; Middle Aged; Prednisolone; Time Factors

6-Mercaptopurine (6MP) pharmacokinetics and red blood cell 6-thioguanine nucleotide (TGN) concentrations were studied in 19 children receiving remission maintenance treatment for lymphoblastic leukemia. There was a high interpatient variation in all the pharmacokinetic parameters measured. The pharmacokinetic parameters measured in two children who subsequently had relapses were within the 95% confidence limits of the 17 other children. There was no difference in 6MP pharmacokinetic parameters with respect to neutropenia either after or before the study. The children who developed neutropenia 10 to 19 days after study had significantly higher TGN concentrations (U = 8; P less than 0.001) and had spent a longer time receiving reduced 6MP dosage in the 12 weeks before the study (U = 19.5; P less than 0.025). TGN concentrations are a better index of a child's ability to form active cytotoxic metabolites than 6MP dose or plasma concentrations.

Topics: Administration, Oral; Child; Child, Preschool; Erythrocytes; Humans; Infant; Kinetics; Leukemia, Lymphoid; Mercaptopurine; Thioguanine

Response to treatment is the most important prognostic factor in children undergoing treatment for acute lymphoblastic leukemia. Factors that interfere with the pharmacokinetic determinants of anti-leukemic compounds may cause a decreased activity of one or more of the drugs included in the treatment protocol. Noncompliance with the prescribed treatment, individual pharmacokinetic differences, interference with oral drug absorption, and different guidelines for dose reduction related to toxicity are some of the factors responsible for a decreased or variable antileukemic activity which may influence treatment results.

Topics: Antineoplastic Agents; Biological Availability; Dose-Response Relationship, Drug; Humans; Individuality; Intestinal Absorption; Kinetics; Leukemia, Lymphoid; Mercaptopurine; Methotrexate; Patient Compliance; Prognosis

Topics: Administration, Oral; Child; Child, Preschool; Drug Administration Schedule; Female; Humans; Kinetics; Leukemia, Lymphoid; Male; Mercaptopurine

The pharmacokinetics of oral 6-mercaptopurine (6MP) was assessed in 20 children with acute lymphoblastic leukemia during maintenance therapy. The AUC was between 0 and 6 X 10 ng X min/ml, and AUC normalized to 1 mg/m2 of 6MP was between 0 and 815 ng X min/ml. Good correlation existed between peak concentrations and AUC (r = 0.866; P less than 0.001). In more than half of the cases there was evidence of prolonged elimination t1/2 or rebound of a serum concentration during the elimination phase corresponding to either an additional compartment or enterohepatic circulation of 6MP. One child did not achieve detectable concentrations on 2 different study days and was switched to a different protocol. The two children who had severe myelotoxicity achieved the largest AUC values per milligram per square meter of 6MP. Our results indicate that pharmacokinetic variability may contribute to either severe myelotoxicity or therapeutic failures. This suggests that monitoring of this drug in children with acute lymphoblastic leukemia may be helpful.

Topics: Administration, Oral; Adolescent; Child; Child, Preschool; Chromatography, High Pressure Liquid; Female; Humans; Kinetics; Leukemia, Lymphoid; Male; Mercaptopurine; Neutropenia

The course of 118 children with acute lymphoblastic leukaemia who had achieved complete remission with a standard induction protocol and had also received meningeal prophylaxis with intrathecal methotrexate (MTX) and cranial irradiation was reviewed. Maintenance chemotherapy consisted of daily 6-mercaptopurine (6-MP), weekly MTX, and monthly vincristine and prednisone. 82 children took 6-MP and MTX in the morning and 36 in the evening. Disease-free survival as determined by Kaplan-Meier analysis was better for children on evening chemotherapy. Regression analysis (Cox proportional hazards model, with evening vs morning schedule as exposure variable, and age at diagnosis, leucocytosis at diagnosis, and sex as covariates) showed that, for those surviving free of disease for longer than 78 weeks, the risk of relapsing was 4.6 times greater for the morning schedule than for the evening one.

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Child; Child, Preschool; Drug Administration Schedule; Humans; Infant; Leukemia, Lymphoid; Mercaptopurine; Methotrexate; Time Factors

Previous studies have failed to establish a direct relationship between behavioral disorders and organic pathology in long-term survivors of childhood acute lymphoblastic leukemia. We evaluated 23 long-term survivors who received central nervous system preventive therapy with cranial irradiation and intrathecal chemotherapy, using neuropsychologic tests and computed tomographic brain scans. The patients were in continuous first remission for 7 to 11 years, and none were receiving chemotherapy. On the basis of their CT scan findings, they were divided into three groups: 10 with normal CT findings, five with intracerebral calcifications, and eight with cortical atrophy. Neuropsychologic test results allowed prediction of CT scan findings with an 87% accuracy (P less than 0.001), indicating a strong correlation between the presence and type of CT scan abnormality and neuropsychologic functioning. Tests that measured verbal memory, attention, and functions correlated with frontal lobe integrity were most powerful in discriminating between groups.

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Child; Child, Preschool; Cognition Disorders; Communication Disorders; Cytarabine; Female; Follow-Up Studies; Humans; Leukemia, Lymphoid; Male; Mercaptopurine; Methotrexate; Neuropsychological Tests; Prednisone; Tomography, X-Ray Computed; Vincristine

Topics: Adolescent; Child; Child, Preschool; Chromatography, High Pressure Liquid; Female; Humans; Infant; Kinetics; Leukemia, Lymphoid; Male; Mercaptopurine; Monitoring, Physiologic

Between 1964 and 1982, 862 patients with acute leukemia who were collected from medical institutions throughout the country had a survival of 5 years or longer. Their remission has been achieved mainly with a combination therapy of vincristine and prednisone in childhood acute leukemia and daunomycin, cytosine arabinoside, 6-mercaptopurine, prednisone (DCMP) regimen in adult acute leukemia. Among 320 relapsed patients, 88 (38.8%) of 227 children had a primary relapse in the marrow, 85 in the central nervous system (CNS), 37 in the testis/ovary, and 13 in a combined site. The large majority of adult relapsed patients relapsed in the marrow. Ninety-three patients who experienced only one relapse had a much longer prolongation of survival, not yet reaching a median over 14 years after diagnosis, compared to those experiencing two or more relapses. Survival curves in five groups of patients divided by length of maintained remission were investigated by the life table method. In children as well as adults, survival duration in patients on 5 or more years maintained remission was significantly longer than that in the other maintained groups. With respect to relation between frequency of CNS relapse and type of CNS prophylaxis, there was no statistically significant difference between patients who received CNS prophylaxis and patients who did not. However, a better survival was observed in patients who received CNS prophylaxis with cranial radiation plus intrathecal methotrexate. Thus, long-term clinical follow-up might provide important information for the therapeutic strategy against acute leukemia.

Topics: Actuarial Analysis; Acute Disease; Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Diseases; Child; Child, Preschool; Cytarabine; Daunorubicin; Female; Health Surveys; Humans; Infant; Japan; Leukemia; Leukemia, Lymphoid; Male; Mercaptopurine; Middle Aged; Nervous System Neoplasms; Prednisolone; Recurrence; Testicular Neoplasms

Aclacinomycin A (ACM) is different from other anthracycline antibiotics in its antitumor activity and clinical effect. We report a case of acute promyelocytic leukemia complicated with severe esophageal ulcer by BH-AC . AMP therapy. The patient was 24 years old. In 1983, he achieved complete remission with BH-AC . DMP therapy but we confirmed relapse in April, 1984. ACM caused nausea, vomiting, diarrhea, alimentary tract bleeding and sore throat, together with a complication of esophageal stenosis. In about half of 10 cases receiving BH-AC . AMP therapy in our hospital, we noticed severe bleeding in the urinary treat, genital organs and alimentary tract. Care should therefore be taken with regard to mucosal injury when ACM therapy is used.

Topics: Aclarubicin; Adult; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Esophageal Stenosis; Esophagoscopy; Humans; Leukemia, Lymphoid; Male; Mercaptopurine; Naphthacenes; Prednisolone

Topics: Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Cyclophosphamide; Daunorubicin; Humans; Leukemia; Leukemia, Lymphoid; Mercaptopurine; Methotrexate; Prednisone; Prognosis; Risk; Thioguanine; Vincristine

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Cytarabine; Dose-Response Relationship, Drug; Female; Humans; Infusions, Parenteral; Leukemia, Lymphoid; Male; Mercaptopurine; Methotrexate; Middle Aged; Prednisolone

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Child; Child, Preschool; Female; Follow-Up Studies; Humans; Infant; Leukemia, Lymphoid; Male; Mercaptopurine; Prednisolone; Prognosis; Vincristine

Controlled clinical trials of therapy for childhood acute leukemia are reviewed in the Children's Cancer & Leukemia Group Studies 1972-1981. The mortality of acute lymphocytic leukemia in children has been reduced about one-half in the past 10 years. Continued progress depends on maintaining our objective of curing all children and in conceiving and testing new ideas that might contribute to cure. Nowadays, the end result of most importance is long-term leukemia-free survival, i.e., the freedom from relapse after off therapy. Advances in the childhood leukemia have paved the way for encouraging progress in the management of the much more common malignancies that affects adults.

Topics: Acute Disease; Antineoplastic Combined Chemotherapy Protocols; Child; Drug Administration Schedule; Humans; Leukemia; Leukemia, Lymphoid; Mercaptopurine; Methotrexate; Prednisolone; Prognosis; Vincristine

Topics: Adult; Female; Humans; Leukemia, Lymphoid; Liver; Mercaptopurine; Partial Thromboplastin Time; Prothrombin Time

Complex clinical, neurological and psychological examination was carried out in 23 children with acute lymphoblastic leukemia (ALL), being in complete initial remission from 5 to 12 years and without medication following the successful intensive therapy according to the protocol 0171 from 2 1/2 to 9 years. Somatic deficiency was observed in 2 children. Slightly hypoplastic bone marrow haemopoesis was found in 2 children. All children had normal haemogram. In 7 children lowered values of E-rosettes and in 3 children lowered levels of serum IgA were detected. Two children were HBsAg positive, in one of them with mild fibrosis was found at biopsy. Pathological neurological findings occurred in 7 children; pathological electromyogram (EMG) and electroencephalogram (EEG) in 8 and 5 children, respectively. Deviations of intellectual development were observed in 13 children. Deviations found can be connected in particular with long-term antileukemic therapy, especially with neurotoxic effects of some components of therapeutic regimen used (methotrexate, brain irradiation).

Topics: Acute Disease; Antineoplastic Combined Chemotherapy Protocols; BCG Vaccine; Child; Child, Preschool; Combined Modality Therapy; Cytarabine; Female; Humans; Leukemia, Lymphoid; Male; Mental Disorders; Mercaptopurine; Methotrexate; Nervous System Diseases; Prednisone; Time Factors; Vincristine

A case of invasive cutaneous Trichophyton rubrum infection complicated the course of a patient undergoing chemotherapy for acute lymphocytic leukemia. This dermatophytic disease was well controlled with ketoconazole. Prior experience with these unusual infections is summarized.

Topics: Humans; Ketoconazole; Leukemia, Lymphoid; Male; Mercaptopurine; Middle Aged; Prednisone; Tinea

Topics: Biological Availability; Child; Humans; Leukemia, Lymphoid; Mercaptopurine

Topics: Antineoplastic Combined Chemotherapy Protocols; Cytoplasm; Drug Resistance; Glucocorticoids; Humans; Leukemia, Lymphoid; Mercaptopurine; Methotrexate; Prednisone; Prognosis; Receptors, Glucocorticoid; Receptors, Steroid; Vincristine

Topics: Animals; Child; Dogs; Drug Evaluation; Hodgkin Disease; Humans; Kinetics; Leukemia, Lymphoid; Mercaptopurine

Twelve boys and 10 girls on similar long term remission maintenance treatment for lymphoblastic leukaemia had 79 random assays of their red cell 6 thioguanine nucleotide ( 6TGN ) concentrations performed as an index of cytotoxic activity generated by oral 6-mercaptopurine ( 6MP ). Correlation between the dose of 6MP and 6TGN was statistically significant in the girls (r = 0.58, P less than 0.001) but not in the boys (r = 0.15). Additionally, as a group the boys tolerated more 6MP (P less than 0.05), despite similar prescribing criteria, but this did not result in a higher mean 6TGN concentration or increased myelotoxicity. It appears that girls develop 6MP cytotoxicity at lower doses and more predictably than boys. If so, this may be relevant to the as yet unexplained but marked sex difference in prognosis apparent in some studies.

Topics: Adolescent; Child; Child, Preschool; Erythrocytes; Female; Guanine Nucleotides; Humans; Leukemia, Lymphoid; Leukocyte Count; Male; Mercaptopurine; Neutrophils; Sex Factors; Thionucleotides

Topics: Aclarubicin; Antineoplastic Combined Chemotherapy Protocols; Child; Cytarabine; Humans; Leukemia, Lymphoid; Male; Mercaptopurine; Naphthacenes; Prednisolone

A survey is given of our present investigations of the pharmacokinetics of 6MP and the effects of the combination of MTX and 6MP on purine and pyrimidine metabolism. Both drugs are used in the oral maintenance therapy of ALL in children. The very low serum-concentrations after oral administration of 6MP and the short serum-half-life-times after intravenous administration point to more efficacy after prolonged intravenous infusion. The penetration of 6MP in the cerebrospinal fluid after intravenous administration could account for (prophylactic) treatment of the CNS in ALL. Pretreatment of leukemic lymphoblasts with MTX results in an increase of intracellular PRPP due to inhibition of purine de novo synthesis. This can be used for an increased incorporation and conversion of 6MP. Thus, increased incorporation and conversion of 6MP can be obtained when 6MP is added to MTX-pretreated leukemic lymphoblasts at that point of time where MTX causes maximal PRPP accumulation. This will result in increased incorporation of 6MP into nucleic acids and thus in enhanced cytotoxicity. Pharmacokinetic and metabolic investigations of 6MP and MTX could lead to a more rational and more effective use of both agents in patients with ALL.

Topics: Animals; Child; Dogs; Half-Life; Humans; Infusions, Parenteral; Leukemia, Lymphoid; Lymphocytes; Mercaptopurine; Methotrexate; Purines; Pyrimidines

The incidence of testicular infiltrates in 68 boys with acute lymphoblastic leukemia in first remission (1974-81), was prospectively investigated through careful clinical exams and routine bilateral biopsies at 2-3 years of remission. All boys were under 14 years of age and they were treated with protocols D.74 and pethema 7/78. Seven patients (10.3%) presented an isolated testicular relapse (ITR) during the chemotherapy period. In 13 out of the 43 testicular biopsies (31%) leukemic infiltrates were found and in other 2 findings were controversial. Three boys, two of them whose previous biopsy was negative, had an ITR, 6 to 18 months after stopping therapy. Finally, other 3 had simultaneous relapses in testes and bone-marrow: one during chemotherapy and two after suppression. In total, 23 patients (33.8%) in first remission had overt or occult ITR. Overall incidence of testes leukemia, is calculated to be 40% in all the group. Incidence of early and occult ITR was higher in boys with initial WBC counts over 20 X 10 9/l. Therapy in ITR generally consisted in local radiotherapy (20-25 Gy), a new induction treatment followed by 2 year maintenance treatment; in 3 patients with early ITR, orchidectomy was also performed and six were given a new preventive SNC treatment. Clinical course in the 7 patients with early ITR was unfavourable in 5 with subsequent hematological relapses and death; one had a long-term disease-free survival (78 + months) and the other was a recent case. 10 out of the 13 patients with occult infiltrates followed in remission and four were of treatment with a follow-up over 64 months. The 3 patients with late ITR were in second remission at 8-14 months after a new cessation of therapy. It may be concluded from this study that prognosis in ITR is related to the phase of presentation: It is unfavourable in cases of early ITR but in cases of occult infiltrates detected by routine biopsies and in late ITR the combined therapy is effective in most cases.

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Bone Marrow; Child; Child, Preschool; Combined Modality Therapy; Humans; Infant; Leukemia, Lymphoid; Male; Mercaptopurine; Methotrexate; Prednisone; Spain; Testicular Neoplasms; Testis; Time Factors; Vincristine

Between July, 1976 and June, 1984, 43 adults with acute lymphocytic leukemia were treated with a V(V') P [vincristine (vindesine), prednisolone] followed by DV(V')MP [daunomycin, vincristine (vindesine), 6-mercaptopurine, prednisolone] and V(V')AP [vincristine (vindesine), 1-asparaginase, prednisolone] regimen. They were all previously untreated and aged 15 and over. Complete remission (CR) was attained in 41.9% of cases by V(V')P alone, the CR rate being increased up to 62.8% by the sequential administration of DV(V')MP, and to 74.4% by the further administration of V(V')AP. The median duration of CR was 5.6 months; it was 10.9 months for patients with the maintenance therapy and 1.3 months for patients without it. For patients who achieved CR, the median survival time (MST) was 21.3 months compared to 2.7 months for those who failed to achieve CR. As for the maintenance therapy, MST was 22.3 months for patients who received it, and 9.5 months for patients who did not. Factors associated with significantly lower rate of CR were: lymphadenopathy and hepatomegaly and/or splenomegaly. The CR rate was somewhat lower for patients aged over 20 and with hyperleukocytosis (above 40,000/cmm). Shorter remissions tended to be associated with ages over 20 and with hepatomegaly and/or splenomegaly. Patients who obtained CR by the sequential administration of the V(V')AP regimen showed somewhat shorter CR duration compared with to those who obtained CR by V(V')P alone and by the sequential administration of DV(V')MP. Survival was significantly shorter for patients who failed to achieve CR, with B-ALL and with hyperleukocytosis. Shorter survival was also observed among patients with ages above 60 compared to those with ages below 20.

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Daunorubicin; Drug Administration Schedule; Female; Humans; Leukemia, Lymphoid; Male; Mercaptopurine; Middle Aged; Prednisolone; Prognosis; Vincristine

Topics: Adolescent; Child; Child, Preschool; Humans; Infusions, Parenteral; Inosine; Leukemia, Lymphoid; Mercaptopurine; Thioinosine

Topics: Actuarial Analysis; Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Female; Humans; Injections, Spinal; Leukemia, Lymphoid; Male; Mercaptopurine; Methotrexate; Middle Aged; Prednisone; Vincristine

The effect of cotrimoxazole on the utilization of 6-mercaptopurine (6MP) was studied in a group of children receiving remission maintenance treatment for lymphoblastic leukaemia (ALL). This was done by measuring the level of an active metabolite of 6MP, 6-thioguanine nucleotide (6TGN), and comparing it both with the drug dose and with subsequent neutropenia in the presence or absence of concurrent cotrimoxazole. In children who were not taken cotrimoxazole, the concentration of 6TGN showed a significant positive correlation with the dose and a significant negative correlation with the absolute neutrophil count 2 weeks later. In those who were taking the antibiotic both these relationships were lost. This suggests that cotrimoxazole can interfere with both the absorption and the cytotoxicity of 6MP and may, in turn, alter its antileukaemic effect.

Topics: Absorption; Adolescent; Child; Child, Preschool; Drug Combinations; Drug Interactions; Female; Guanine Nucleotides; Humans; Leukemia, Lymphoid; Male; Mercaptopurine; Sulfamethoxazole; Thionucleotides; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

An assay for 6-thioguanine (6-TG) nucleotide, a major metabolite of the cytotoxic drugs azathioprine, 6-mercaptopurine and 6-thioguanine in human red blood cells (RBCs) has been developed. The metabolite was not detected in RBCs when azathioprine or 6-mercaptopurine was incubated with whole blood in-vitro. The assay for intracellular 6-TG nucleotide is specific and requires 8 X 10(8) RBCs (100 microliters packed cells) for which the limit of sensitivity is 30 pmole 6-TG nucleotide. Pre-dose blood samples were obtained, 12 h after the last azathioprine dose, from 10 renal transplant recipients with stable functioning cadaver grafts on a total daily dose of 150 mg azathioprine. The mean 6-TG nucleotide concentration was 171 pmole/8 X 10(8) RBCs (s.d. = 84). The assay is also suitable for use in measuring 6-TG nucleotide in the RBCs of leukaemic children undergoing 6-mercaptopurine treatment.

Topics: Azathioprine; Erythrocytes; Guanine Nucleotides; Humans; In Vitro Techniques; Leukemia, Lymphoid; Mercaptopurine; Thioguanine; Thionucleotides

Topics: Administration, Oral; Adolescent; Animals; Biological Availability; Child; Child, Preschool; Chromatography, High Pressure Liquid; Female; Humans; Injections, Intravenous; Kinetics; Leukemia, Lymphoid; Macaca mulatta; Male; Mercaptopurine

Topics: Asparaginase; Child; Cyclophosphamide; Cytarabine; Daunorubicin; Drug Therapy, Combination; Humans; Leukemia, Lymphoid; Mercaptopurine; Methotrexate; Prednisolone; Prognosis; Recurrence; Vincristine

6-Mercaptopurine is extensively used in the treatment of childhood lymphoblastic leukaemia to prolong the duration of remission achieved with other drugs. The response to remission maintenance therapy varies widely. We investigated the relationship between red blood cell 6-thioguanine nucleotide, a metabolite of 6-mercaptopurine, and myelosuppression in 22 children with acute lymphoblastic leukaemia in remission. The peripheral neutrophil count was used as an index of myelosuppression. 6-Mercaptopurine dose was related to 6-thioguanine nucleotide concentration (r = 0.4; P less than 0.001; n = 90; y = 18.51 + 0.36 x). Large individual variations around the regression line are observed. Neither 6-mercaptopurine dose nor 6-thioguanine nucleotide concentration was related to the neutrophil count at the time of sampling (day 0) or 7 days later. Both 6-mercaptopurine dose and 6-thioguanine nucleotide concentration correlated with the neutrophil count at day 14 (r = -0.33; P less than 0.01; n = 90 and r = -0.3; P less than 0.01; n = 90 respectively). This delay is compatible with a cytotoxic action on bone marrow stem cells. Excluding children with other, uncontrolled, potentially myelosuppressive influences the correlation between 6-thioguanine nucleotide concentration and neutropenia improved (r = -0.6; P less than 0.001; n = 37). A significant degree of neutropenia was observed by day 14 if the 6-thioguanine nucleotide concentration (day 0) was greater than 210 pmol/8 X 10(8) RBCs. The assay of 6-thioguanine nucleotide may highlight those individuals with pharmacokinetic resistance. Two children on continuous high dose 6-mercaptopurine, had low red blood cell 6-thioguanine nucleotide concentrations and neutropenia was not observed.

Topics: Adolescent; Agranulocytosis; Bone Marrow Diseases; Child; Child, Preschool; Erythrocytes; Female; Humans; Leukemia, Lymphoid; Male; Mercaptopurine; Neutropenia; Thioguanine

One hundred four children with acute lymphoblastic leukaemia were diagnosed at the University Hospital, Kuala Lumpur, Malaysia, between 1976 and 1982; 87 were evaluable with respect to treatment. They were divided into good prognosis (GP) and bad prognosis (BP) groups based on their initial total white cell count, their treatment differing only during the maintenance phase. Remission was achieved in 82 patients (94%) of whom ten (12%) subsequently died in remission from infection. Twenty-eight (34%) relapsed while on treatment and three while off therapy. Eleven patients ceased treatment after 3 yr of continuous complete remission (CCR). Three of these later relapsed, two within the first year. Survival in CCR was significantly better in the GP group up to 30 months, after which the difference diminished. There was no difference in survival between boys and girls. The overall disease-free survival at 3 yr and 5 yr was 40% and 25%, respectively, with a median follow-up period of 20 months (range 4-69 months). The reasons for the relatively low survival rates as compared with those in developed countries are discussed.

Topics: Antineoplastic Combined Chemotherapy Protocols; Child; Child, Preschool; Doxorubicin; Female; Humans; Leukemia, Lymphoid; Male; Meningeal Neoplasms; Mercaptopurine; Methotrexate; Prednisolone; Prognosis; Vincristine

Earlier studies suggested that the dose of 6-mercaptopurine (6-MP) can be reduced substantially when the drug is given with allopurinol. We studied the effect of allopurinol on the kinetics of oral and intravenous 6-MP. Studies conducted initially in rhesus monkeys and subsequently in man with 6-MP doses of 100 mg/m2 and 75 mg/m2, demonstrated that allopurinol pretreatment resulted in a nearly 400% increase in peak plasma concentration of oral 6-MP in monkeys (from a mean of 0.54 microM to a mean of 2.1 microM) and a 500% increase in man (0.74 microM to 3.7 microM). Allopurinol pretreatment also led to a 300% increase in plasma AUC in monkeys after oral 6-MP (from a mean of 121 microM/min to a mean of 391 microM/min) and a 500% increase in AUC in man (from a mean of 142 microM/min to a mean of 716 microM/min). In contrast, allopurinol pretreatment had no effect on the kinetics of intravenous 6-MP. This difference was found to be due to inhibition of first-pass metabolism of oral 6-MP as the result of the action of allopurinol on liver or intestinal xanthine oxidase. Our results indicate that, although dose reduction of oral 6-MP given in conjunction with allopurinol is appropriate, it is not necessary when 6-MP is injected intravenously.

Topics: Administration, Oral; Allopurinol; Animals; Biological Availability; Drug Interactions; Humans; Injections, Intravenous; Kinetics; Leukemia, Lymphoid; Macaca mulatta; Mercaptopurine; Metabolic Clearance Rate; Species Specificity

31 adults suffering from acute leukemia were followed for a period of more than 5 years after achieving complete remission. Maintenance chemotherapy consisted of antimetabolite treatment (mercaptopurine + methotrexate) as well as COAP reinduction every 3 months. Chemotherapy was stopped if the first complete remission lasted for 3 years ("long term remission"). This was the case in 8 out of 31 remission patients (26%). Analysis of hematological parameters at diagnose for long term remission patients revealed that the initial leukocyte count was of prognostic significance.

Topics: Acute Disease; Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Cytarabine; Female; Follow-Up Studies; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Leukocyte Count; Male; Mercaptopurine; Methotrexate; Middle Aged; Prednisone; Prognosis; Time Factors; Vincristine

Topics: Adolescent; Biological Availability; Child; Child, Preschool; Dose-Response Relationship, Drug; Erythrocytes; Female; Guanine Nucleotides; Humans; Leukemia, Lymphoid; Leukocyte Count; Male; Mercaptopurine; Neutrophils; Thionucleotides

Topics: Adult; Drug Therapy, Combination; Female; Fever; Humans; Leukemia, Lymphoid; Mercaptopurine

24 children with low risk acute lymphoblastic leukemia (ALL) in first relapse were re-treated with an aggressive protocol. Therapy of the first episode had adopted two different but equivalent approaches (SAKK-ALL "low risk" 76 and CALGB protocol 7611). With one exception, relapse occurred in all children before discontinuation of therapy. complete remission was achieved in 20 of the 24 children (83%). Five of 11 children in whom the length of the second remission could be evaluated had, at the time of the cutoff, been in continuous remission for 18 to 40 months. The therapy displayed considerable toxicity. From this study it is concluded that remission is achieved in the majority of children with first relapse of ALL, but that the remission can be maintained beyond 18 months only in a few children.

Topics: Adolescent; Antineoplastic Agents; Asparaginase; Child; Child, Preschool; Doxorubicin; Drug Therapy, Combination; Female; Humans; Injections, Spinal; Leukemia, Lymphoid; Male; Mercaptopurine; Methotrexate; Prednisone; Prognosis; Vincristine

Between January 1979 and December 1980 64 children with acute lymphoblastic leukemia were treated in 9 pediatric clinics in austria according to the BFM study 76/790-protocol. For remission induction all patients received an 8 week multidrug regimen (West-Berlin ALL-protocol). High risk patients were defined according to a risk score at diagnosis and additionally treated with a 6 week reinforced reinduction protocol during the first half year after diagnosis. Maintenance therapy was stopped after about 22 months. The life table-analysis after 30 months showed a 75.5% disease free survival for the total group of patients. Compared with a control group of 228 patients treated between 1974 and 1980 in 9 different clinics in Austria according to 3 consecutive national treatment regimens (modifications of Memphis protocol VII and VIII), therapeutic results were markedly improved. After a follow-up of 36 to 90 months the overall oumulative remission rate was 37.7%. The results could be improved especially in the group of high risk patients for replase by 35% in contrast to the historical studies. A prognostic difference between low- and high risk-patients was not seen in the BFM study (84.3% vs. 69.9%). Without doubt, the marked improvement of prognosis is due to the intensification of therapy.

Topics: Antineoplastic Agents; Asparaginase; Child; Child, Preschool; Cyclophosphamide; Cytarabine; Daunorubicin; Dexamethasone; Doxorubicin; Drug Therapy, Combination; Female; Humans; Infant; Injections, Spinal; Leukemia, Lymphoid; Male; Mercaptopurine; Methotrexate; Prednisone; Risk; Thioguanine; Vincristine

The inter-Sertoli junctions of children aged between 5 and 12 years, affected by acute lymphoblastic leukaemia, were analyzed in sections and freeze-fracture replicas. The testicular biopsies were performed at the end of therapy, when patients were in continuous remission for over 30 months. Chemotherapy does not seem to affect the development of junctions that were studied in sections and freeze fracture. Two age groups were considered (I, 5 to 8 years; II, 9 to 12 years). In age group I, oval Sertoli cells were connected by occasionally focal points of fusion, which in replicas appeared as scattered, interrupted ridges on the P face and grooves on the corresponding E face. In age group II Sertoli cells presented cytoplasmic extensions and interdigitations. Tight junctions appeared close to one another in conventional sections. Freeze fracture evidenced extensive although isolated areas formed by intervining strands. Lanthanum penetrated freely the intercellular spaces and gap junctions were observed in both age groups. The results suggest that tight junctions formation is initiated long before puberty; a progression in the complexity of the strand organization is present as the tubules mature; the strands reorganize in parallel and continuous rows only at puberty.

Topics: Animals; Antineoplastic Agents; Biopsy; Child; Child, Preschool; Drug Therapy, Combination; Humans; Intercellular Junctions; Leukemia, Lymphoid; Male; Mercaptopurine; Methotrexate; Mice; Prednisone; Rabbits; Rats; Sertoli Cells; Testis; Vincristine

Between January 1974 and November 1978, 41 consecutive increased risk (age less than 24 months or less than 120 months, or leukocyte count greater than 30,000/mm3) patients with acute lymphoblastic leukemia (ALL) were entered on two consecutive treatment protocols which employed intermediate dose methotrexate (IDM). IDM was employed for central nervous system prophylaxis and systemic intensification. It was anticipated that the avoidance of prophylactic cranial irradiation would result in a lower incidence of longterm central nervous system sequelae. Twenty-two children and adolescents were entered on the first study (IDM X 3) which employed three courses of IDM (500 mg/m2) and six doses of intrathecal (IT) methotrexate (MTX). Nineteen children and adolescents were entered on the second study (IDM X 6) which employed six courses of IDM (3-500 mg/m2 and 3-1500 mg/m2), six doses of IT MTX and three additional doses of triple IT chemotherapy (MTX, cytosine arabinoside, and hydrocortisone or dexamethasone). The cumulative percentage of patients who remained in continuous complete remission was 30% for IDM X 3 and 57% for IDM X 6. This difference was statistically significant (P = 0.046; and BM + CNS, I-using IDM X 6. The cumulative incidence of primary CNS relapse was 36.4% for IDM X 3 and 29.9% for IDM X 6. This difference was not statistically significant (P = 0.44). The use of more intensive therapy with IDM and triple IT chemotherapy did improve the duration of continuous, complete remission but did not decrease the incidence of primary CNS relapse in increased risk patients.

Topics: Adolescent; Asparaginase; Child; Child, Preschool; Cytarabine; Dexamethasone; Drug Administration Schedule; Female; Humans; Hydrocortisone; Infant; Injections, Spinal; Leukemia, Lymphoid; Liver; Male; Mercaptopurine; Methotrexate; Prednisone; Vincristine

Sixty-two adult patients with acute lymphoblastic leukemia (ALL) were treated with an induction regimen including vincristine, daunorubicin and prednisone (VDP) followed by CNS prophylaxis. Forty-five patients (72.5%) achieved complete remission (CR). The CR were maintained with daily 6-MP and weekly MTX. Monthly reinduction cycles with vincristine and prednisone (plus daunorubicin every three courses) were also given. Median duration of CR was 10.4 months. Overall survival was 17.4 months. The remission rate and length of CR were studied in relation to the clinical and hematological features present at diagnosis. CR rate was adversely influenced by age only over 40 and by tumoral presentation. The length of remission was negatively influenced by tumoral presentation, CNS involvement, high circulating blast count, L2 and L3 cytology, and T or B immunological phenotype. Multiple regression analysis confirmed the weight of FAB morphology in determining the length of remission. Among L2 adult patients, tumoral presentation appears to be the major unfavourable prognostic factor.

Topics: Adolescent; Adult; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Child; Daunorubicin; Drug Therapy, Combination; Female; Humans; Leukemia, Lymphoid; Male; Meningeal Neoplasms; Mercaptopurine; Methotrexate; Middle Aged; Prednisone; Vincristine

Topics: Adolescent; Adult; Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Daunorubicin; Drug Therapy, Combination; Female; Humans; Leukemia, Lymphoid; Male; Mercaptopurine; Middle Aged; Prednisolone; Vincristine

Topics: Antineoplastic Agents; Child; Child, Preschool; Female; Humans; Infant; Leukemia, Lymphoid; Male; Mercaptopurine; Methotrexate; Prednisolone; Singapore; Vincristine

Children with acute lymphoid leukemia (ALL) were treated according to two protocols. A group of 65 patients in which prognostic factors were no taken into account were treated with a combination of vincristine, asparaginase and prednisone to induce remission, followed by neuromeningeal prophylaxis with intraraquideal methotrexate and cranial irradiation with 2400 rads, two years maintenance therapy with 6-mercaptopurine and methotrexate, and then reinforcing chemotherapy, BCG scarification and injection of irradiated leukemic cell. No relapses were observed in the first 4.5 years. After 7.5 year, general survival was of 60 per 100, with 44 per 100 disease-free. A group of ALL children having a good prognosis were treated as indicated but adding adriamycin during the induction of remission and vindesine during the maintenance period. During the first three years no relapses were seen, and the general survival was 82 per 100, including a high proportion of disease-free children.

Topics: Antineoplastic Combined Chemotherapy Protocols; Asparaginase; BCG Vaccine; Child; Combined Modality Therapy; Doxorubicin; Humans; Leukemia, Lymphoid; Meningeal Neoplasms; Mercaptopurine; Methotrexate; Prednisone; Prognosis; Vincristine; Vindesine

We describe two adolescent girls with acute lymphoblastic leukemia (ALL) whose leukemia cells were near-haploid. Their lymphoblasts stained in a block pattern with periodic acid Schiff and had "common ALL" surface markers confirmed by indirect immunofluorescence. Each patient had two populations of blasts, one near-haploid and one hyperdiploid, which was an exact doubling of the near-haploid karyotype. The first patient had a predominant population of cells with 26 chromosomes and a few with 52, while the second had a predominance of cells with 56 and a minority with 28. Flow cytometric analysis of DNA content initially detected the minor near-haploid population in the second patient, which was confirmed later by cytogenetic review of the marrow sample. In addition to our two patients, only four patients have been reported with near-haploid ALL. Of these six, five were girls, five were adolescents, and five had short survivals (median, 10 mo). All six had disomy of chromosome 21 with or without disomy for chromosomes 10, 14, 18, or X (four patients each). Thus, near-haploid ALL may represent a unique subgroup of ALL with a poor prognosis. To detect these and other possible subgroups, we have included cytogenetic analysis and flow cytometric analysis of DNA content in our initial evaluation of patients with ALL.

Topics: Acute Disease; Adolescent; Bone Marrow Examination; Brain Neoplasms; Child; Daunorubicin; Female; Haploidy; Humans; Injections, Spinal; Karyotyping; Leukemia, Lymphoid; Mercaptopurine; Methotrexate; Neoplasm Metastasis; Prednisone; Prognosis; Vincristine

The in vivo effect of various cytotoxic drugs and cranial irradiation on neutrophil chemotaxis was tested in 62 children with acute lymphoblastic leukaemia and in 10 patients with other malignant disease. Cranial radiotherapy had a transient adverse effect on neutrophil chemotaxis after completion of the course which was most marked in children. Methotrexate (MTX) and 6-mercaptopurine (6-MP) alone and in combination had a variable effect of chemotaxis, which was most marked nine days after the end of the course. The effect of 6-MP was clearly dose-related, but continuous therapy (75 mg/m2 day) had the greatest inhibitory effect of all the regimens tested. The in vitro effect was studied in 48 leukaemics and in 85 controls (adults and children); all the patients with leukaemia had been off treatment for at least six months. No difference was found between the effects of drugs tested on control or leukaemic cells. The greatest inhibitory effect was found in vinblastine, adriamycin, 6-MP, and vincristine, all of which were closely dose-dependent, MTX, prednisolone, and asparaginase had no effect on chemotaxis when tested in this way.

Topics: Adolescent; Adult; Antineoplastic Agents; Brain Neoplasms; Chemotaxis, Leukocyte; Child; Dose-Response Relationship, Drug; Drug Therapy, Combination; Humans; Leukemia, Lymphoid; Mercaptopurine; Methotrexate; Neutrophils; Time Factors

This is a review of the progress achieved in the treatment of acute lymphoblastic leukaemia, based on a series of 1580 children treated in Prof. Jean Bernard's unit, Paris, from 1956 to 1976. The children are retrospectively divided into three prognostic classes and five therapeutic categories. The benefits obtained from successive additions to the therapeutic armentarium during that period are conspicuous in all classes and categories and particularly striking in children with poor initial prognosis. The role of each component of the therapeutic measures applied is discussed.

Topics: Adolescent; Child; Child, Preschool; Cyclophosphamide; Daunorubicin; Humans; Infant; Leukemia, Lymphoid; Male; Meningeal Neoplasms; Mercaptopurine; Methotrexate; Prednisone; Testicular Neoplasms; Vincristine

Topics: Antineoplastic Agents; Asparaginase; BCG Vaccine; Child; Child, Preschool; Drug Therapy, Combination; Female; Humans; Infant; Leukemia, Lymphoid; Male; Mercaptopurine; Methotrexate; Prednisolone; Vincristine

The cooperative study COALL-80 is derived from the BFM-78-study. The aim of the study is a reduction of the initial therapy-morbidity and -mortality without loss of efficacy by omitting asparaginase from the four drug-induction regimen and interposing it between induction- and CNS-therapy phase. The expected two years disease free survival rate of a pilot study will be 82%. This finding is hitherto comparable with the BFM-study results.

Topics: Adolescent; Child; Child, Preschool; Cyclophosphamide; Cytarabine; Female; Humans; Infant; Leukemia, Lymphoid; Male; Mercaptopurine; Methotrexate; Prednisone; Prognosis; Vincristine

Seventeen adult patients with previously untreated acute lymphoblastic leukaemia (ALL) were entered into a schedule of chemotherapy in which 3 combinations, each of 4 drugs, were administered in a predetermined cyclical rotation in combination with cranial irradiation and intrathecal injections of methotrexate. Of the 17 patients, 16 completed induction therapy and 15 (94%) entered remission. The only patient with T-ALL died before receiving any therapy. The median survival for all patients (17) was 22 months. Meningeal leukaemia did not occur during the haematological remission phase although 3 patients developed this complication following relapse. The authors conclude that the addition of cyclophosphamide and cytosine arabinoside to vincristine/prednisone provides excellent remission induction but the aggressive maintenance schedule employed has not led to significant long-term survival.

Topics: Adolescent; Adult; Antineoplastic Agents; Cyclophosphamide; Cytarabine; Daunorubicin; Drug Therapy, Combination; Female; Humans; Leukemia, Lymphoid; Male; Mercaptopurine; Methotrexate; Middle Aged; Prednisolone; Thioguanine; Vincristine

Topics: Cell Line; Cell Survival; Cytarabine; Daunorubicin; Dose-Response Relationship, Drug; Humans; Leukemia, Lymphoid; Mercaptopurine; Methotrexate; Prednisolone

Topics: Adult; Blood Transfusion; Diuretics; Drug Therapy, Combination; Female; Humans; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Mercaptopurine; Middle Aged; Plasma Substitutes

In a prospective, nonrandomized trial clinical (initial WBC and chest film) and immunological (surface immunoglobulin and rosetting with pretreated sheep red blood cells) criteria were used to stratify 69 children with previously untreated acute lymphoid leukemia (ALL). Forty of 61 evaluable patients had low-risk ALL (initial WBC less than or equal to 20,000/mm3, no mediastinal mass) and were treated less intensively. Twenty-one of 61 patients had high-risk ALL (initial WBC greater than 20,000/mm3 and/or mediastinal mass) and were treated more intensively. Of the high-risk patients 15 had non-T non-B and 6 T ALL. Sixty of 61 patients went into complete remission. After a median observation period of 27 months, 32 of 40 low-risk, 7 of 14 high-risk non-T non-B, and none of 6 high-risk T ALL patients were in continuous first remission. Thirty-six of 40 low-risk, 9 of 15 high-risk non-T non-B, and none of 6 T ALL patients were alive. Despite more intensive treatment, the duration of remission and the survival were significantly shorter in the high-risk than in the low-risk patients. Among the high-risk ALL, non-T non-B ALL did better than T ALL.

Topics: Adolescent; Asparaginase; B-Lymphocytes; Child; Cyclophosphamide; Drug Therapy, Combination; Humans; Leukemia, Lymphoid; Leukocyte Count; Mercaptopurine; Methotrexate; Prednisone; Prognosis; Receptors, Antigen, B-Cell; Remission, Spontaneous; Risk; T-Lymphocytes; Vincristine

Eighty-four children presenting with acute lymphoblastic leukaemia were entered into a trial designed to test the effect on host toxicity of regular drug-free periods during chemotherapy. Patients received the same total dose of drugs either continuously (daily), intermittently (a 5 d course every 3 weeks) or in an intermediate way between these two (a 14 d course followed by a 7 d gap). Mean neutrophil counts were lower in the intermittent group and fell significantly at 6 week intervals, after courses which included prednisolone and vincristine in addition to methotrexate and 6-mercaptopurine. Mean lymphocyte counts, mitotic response to phytohaemagglutinin and plasma immunoglobulin levels were significantly lower in the continuous group. The results in the intermediate group fell between those of the other two groups. All six remission deaths occurred in the 42 patients in the continuous group, who had a much higher incidence of infections (mostly viral and protozoal) than the other two groups. It is concluded that the intermittent chemotherapy schedule permits the maintenance of a lymphocyte population size and function which provides a satisfactory level of defence against infection without prejudice to its anti-leukaemic effect.

Topics: Adolescent; Child; Child, Preschool; Drug Administration Schedule; Female; Humans; Immunoglobulins; Leukemia, Lymphoid; Leukocyte Count; Lymphocytes; Mercaptopurine; Methotrexate; Mitosis; Neutrophils; Pneumonia

Topics: Adolescent; Antineoplastic Agents; Asparaginase; Child; Child, Preschool; Cytarabine; Daunorubicin; Drug Therapy, Combination; Evaluation Studies as Topic; Female; Humans; Infant; Leukemia, Lymphoid; Male; Mercaptopurine; Methotrexate; Prednisolone; Radioisotope Teletherapy; Radiotherapy Dosage; Vincristine

Topics: Antineoplastic Agents; Asparaginase; Child; Cyclophosphamide; Daunorubicin; Drug Administration Schedule; Drug Therapy, Combination; Humans; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Mercaptopurine; Methotrexate; Prednisolone; Radiotherapy Dosage; Vincristine

From 1971 through 1979 145 newly diagnosed patients with ALL have been treated within a series of consecutive studies. Study I corresponds to branch A of the 1972 DAL study. In the following studies the induction therapy has been escalated stepwise with the continuation therapy remaining mostly unchanged. Thereby the disease free survival rates increased from 75 to 94% after one year and from 32 to 60% after 4 years respectively. CNS-relapse mainly occurred during the second year of treatment. Their incidence rose from 5% to more than 10% in connection with a change in the radiation portal. Since another correction of the portals with special consideration of the paramedian lower border of the skull base no more CNS-relapses have been observed until now. The actual cooperative ALL-study follows a modified BFM-protocol with postponed asparaginase in hoping to achieve reduced initial morbidity and at least equal good survival times.

Topics: Child; Cyclophosphamide; Drug Therapy, Combination; Humans; Leukemia, Lymphoid; Mercaptopurine; Methotrexate; Prednisone; Vincristine

55 children suffering from acute lymphoblastic leukemia were treated wih prednisone, vincristin-sulfate, daunorubicine and L-asparaginase (1st month), 6-mercapto-purine, cytosine-arabinoside. cyclophospamide, methotrexate-i.th. and cranial irradiation (2nd month). Maintenance-therapy comprised 6-mercapto-purine, cyclophosphamide and methotrexate-i.v. Serial EEG-examination were done in most of them during the course of treatment. 4 children presented with meningeal leukemia at the time of diagnosis. Their EEGs showed moderate slowing before treatment and at the end of the first month. One of them suffered a focal convulsion two days after the last VCR/daunorubine-injection. All EEG-changes were completely reversible later on. 3 patients showed severe focal EEG-disturbances and convulsions during serious neurological complications (intracranial bleeding, rubella-encephalitis). The remaining patients were free of complications at the time of the EEG-examination. Before therapy 24% of them presented normal findings, 57% slightly and 19% moderately abnormal EEGs. At the end of the first month there was an increase of moderate and severe EEG-slowing to 37% and 23%, only 11% of findings were normal. Improvement during the second month of therapy led to 37% normal and 57% slightly abnormal EEG-findings at its end. After maintenance-therapy of 1/2--1 year duration there were 65% normal EEGs and no moderate and severe disturbances any longer. Quantitative spectral analysis of the EEG in 6 additional children revealed similar changes.

Topics: Adolescent; Asparaginase; Berlin; Child; Child, Preschool; Cyclophosphamide; Cytarabine; Daunorubicin; Drug Therapy, Combination; Electroencephalography; Germany, West; Humans; Infant; Leukemia, Lymphoid; Male; Meningeal Neoplasms; Mercaptopurine; Methotrexate; Prednisone; Registries; Vincristine

Calcification occurring in the basal ganglia in children with acute lymphocyte leukemia following therapy is uncommon and to the best of our knowledge has not been reported prior to therapy. Eleven cases of bilateral symmetrical calcification in the basal ganglia were noted in 2350 CT scans, two being in children with acute lymphocytic leukemia. In one of the two cases, calcification was present prior to therapy.

Topics: Basal Ganglia Diseases; Calcinosis; Child; Child, Preschool; Drug Therapy, Combination; Humans; Leukemia, Lymphoid; Male; Mercaptopurine; Methotrexate; Prednisone; Tomography, X-Ray Computed; Vincristine

Combination chemotherapy with VM-26 and ara-C was given to 14 children with acute lymphocytic leukemia who had not responded to initial treatment with prednisone, vincristine, daunomycin, and asparaginase. Nine of these patients had also received ara-C. At diagnosis, five children were classified as having standard prognostic features and nine as being at high risk for treatment failure. The drug combination was administered by vein twice a week for four weeks at dosages of 165 mg/m2 for VM-26 and 300 mg/m2 for araC. Nine complete remissions, five in patients with high-risk leukemia, were induced with acceptable toxicity; all 9 subsequently were given continuation therapy with oral mercaptopurine and methotrexate. Four of the 9 patients have relapsed at 2--21 months. All treatment was stopped in 2 patients after 30 months of complete remission. Combinations of VM-26 and ara-C represent an alternative remission induction treatment for patients who fail to attain initial remission with agents of established effectiveness. These agents may especially benefit patients with prognostic features indicating a high risk of treatment failure.

Topics: Adolescent; Antineoplastic Agents; Bone Marrow Diseases; Child; Child, Preschool; Cytarabine; Drug Resistance; Drug Therapy, Combination; Female; Humans; Infant; Leukemia, Lymphoid; Male; Mercaptopurine; Methotrexate; Podophyllotoxin; Remission, Spontaneous; Teniposide

Intensive chemotherapy according to the West Berlin protocol was given in 15 children with acute lymphoblastic leukaemia with bone marrow recurrence after an initial remission period of 12 months or longer. Treatment of first episode had followed the 1971 recommendation of the German working group for research and treatment of childhood leukaemia (Memphis VII protocol). One child died from Pseudomonas septicaemia during relapse treatment, the other 14 achieved renewed complete remission for 4 to 50 months. All 5 children in whom the initial remission had lasted less than 20 months had another recurrence after 12 to 17 months. Four out of the 9 patients with an initial remission period of 20 months or longer had another bone marrow relapse after 5 to 36 months. Five children are in continuing second remission for 26 to 50 months, 4 of them already off treatment (for the last 5 to 12 months). The results show that in certain cases of relapse of acute lymphoblastic leukaemia of childhood a new chance of long-term remission and perhaps cure exists, particularly after long initial remission, when a suitable intensive treatment regime is followed.

Topics: Bone Marrow; Child; Child, Preschool; Cyclophosphamide; Female; Humans; Infant; Leukemia, Lymphoid; Male; Mercaptopurine; Methotrexate; Prednisone; Recurrence; Skull; Vincristine

Topics: Antineoplastic Agents; Child, Preschool; Drug Therapy, Combination; Humans; Leukemia, Lymphoid; Male; Mercaptopurine; Methotrexate; Prednisolone; Vincristine

Twenty-two children with acute lymphocytic leukemia (ALL) who had relapsed while on therapy and for whom remissions were successfully reinduced were maintained with a combination of methotrexate, daunomycin, 6-mercaptopurine, prednisone, and vincristine (Djerassi-methotrexate with BOMB). The median duration of remission was 35 weeks (range, five to 364+ weeks). Of 8 children (36%) did not relapse while receiving this therapy, 4 are off all therapy (durations of remissions, 40+, 97+, 132+, and 216+ weeks). Improved responses were found in children with platelet counts of greater than 10(5)/mm3 at the time of index relapse. Intrathecal chemotherapy seemed to greatly prolong the duration of remission for 16 children when compared to those children who did not receive IT therapy (45.5 vs. 24 weeks). No central nervous system relapses occurred. This maintenance regimen for children with previously relapsed ALL appears to be effective and worth additional clinical trials.

Topics: Adolescent; Antineoplastic Agents; Child; Child, Preschool; Daunorubicin; Drug Administration Schedule; Drug Therapy, Combination; Evaluation Studies as Topic; Female; Humans; Injections, Spinal; Leukemia, Lymphoid; Male; Mercaptopurine; Methotrexate; Prednisone; Prognosis; Recurrence; Remission, Spontaneous; Vincristine

11 children, aged between 18 months and 14 years, suffering from acute leukemia showed extremely long-term survival lasting 10-28 years, at an average of 18 years. 9 cases had acute lymphatic leukemia of the low risk group (apart from their age). 2 girls had acute myelogenous leukemia of the promyelocytic type, 1 of them belonging to the high risk group. Treatment was given for 2-10 years, at an average of 5 years, mostly in the form of modified 'monotherapy'. Total therapy, CNS prophylaxis (irradiation and methotrexate intrathecally) was not employed. The children were mostly controlled as outpatients to avoid the danger of hospital infections and to give them a better psychological ambiance. 3 grown-up patients are parents of altogether 6 children, which proves the possibility of normal progeny. The description of these exceptional cases, however, should not lead to the abolition of the present, very promising, intensive therapy with a high percentage of 5-year survivals.

Topics: Adolescent; Ambulatory Care; Antineoplastic Agents; Child; Child, Preschool; Female; Follow-Up Studies; Hospitalization; Humans; Infant; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Methotrexate; Pediatrics; Prednisone; Pregnancy; Time Factors; Vincristine

Topics: Adult; Bone Marrow Transplantation; Child; Cytarabine; Humans; Leukemia, Lymphoid; Male; Mercaptopurine; Methotrexate; Podophyllotoxin; Prognosis; Transplantation, Homologous

Topics: Adolescent; Adult; Antineoplastic Agents; Asparaginase; Aziridines; Bone Marrow Transplantation; Carubicin; Cyclophosphamide; Drug Therapy, Combination; Graft Survival; Humans; Immunosuppressive Agents; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Mercaptopurine; Methotrexate; Middle Aged; Organophosphorus Compounds; Prednisolone; Purines; Thioguanine; Transplantation, Homologous; Vincristine

19 months after the clinical manifestation of acute lymphoblastic leukaemia, Hodgkin's disease, stage Ia, of the cervical lymphnodes developed in a 10 year old girl during continuous complete remission of leukaemia under chemotherapy. After a regional irradiation and after completing the antileukamic therapy the patient is at present off therapy, healthy and without signs of relapse of both malignant systemic diseases. The coincidence of acute lymphoblastic leukaemia in children with other malignant neoplasias is rare. The expected frequency of second malignancies and the theories concerning oncogenesis are shortly reviewed.

Topics: Child; Female; Hodgkin Disease; Humans; Leukemia, Lymphoid; Lymph Nodes; Mercaptopurine; Methotrexate; Methylprednisolone; Neck; Neoplasms, Multiple Primary; Remission, Spontaneous; Vincristine

Eight successful pregnancies and one spontaneous abortion have been observed in 5 women belonging to a group of 212 Nordic children who had their antileukemic therapy discontinued before January 1, 1978. Furthermore a young leukemic man was the father of a healthy child after 4 years of intensive cytostatic therapy. No malformations have been observed in the progeny of these treated individuals.

Topics: Abortion, Spontaneous; Adolescent; Adult; Cyclophosphamide; Female; Follow-Up Studies; Humans; Leukemia, Lymphoid; Male; Mercaptopurine; Methotrexate; Prednisone; Pregnancy; Vincristine

In an attempt to improve remissions and survivals in previously treated patients with adult acute leukemia, we gave Adriamycin, vincristine, and prednisone for induction therapy, followed by 6-mercaptopurine and methotrexate for maintenance therapy to patients attaining complete remission (CR). The study group consisted of 18 patients with acute myeloblastic leukemia (AML), ten with acute lymphoblastic leukemia, and one with acute undifferentiated leukemia. Only one patient had previously received Adriamycin. Overall, there were ten CRs and two partial remissions. The five CRs and one partial remission in patients with AML occurred among those with one prior induction attempt; none of the eight AML patients with more than one prior induction attempt responded. The actuarial median duration of CR was 15 weeks and was similar for AML and acute lymphoblastic leukemia patients. Responders had a longer median survival (30 weeks) than nonresponders (9 weeks). Thus, although a reasonable number of responses in previously treated patients were obtained with this program, improvements in maintenance therapy are clearly needed.

Topics: Antineoplastic Agents; Doxorubicin; Drug Therapy, Combination; Female; Humans; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Methotrexate; Prednisone; Vincristine

Two cases of fatal pneumopathy during cytostatic therapy for acute lymphatic leukemia of childhood, are reported with pathoanatomical lung findings and general clinical features. Histology revealed massed atypical epithelial proliferation in the bronchiolar terminal pathways (tumourlets) with multinucleated polymorphic giant cells beside pulmonary fibrosis. As causative factors for pulmonary chages hypersensitivity reactions, direct toxicity, or pharmacologic effects are discussed. Formal pathogenesis is explained by an impairment of endothelial cells in alveolar capillaries followed by permeability disorders and interstitial edema with disturbed perfusion. Disseminated intravasal microthrombi are frequent. Restitution to integrity appears possible only under favorable conditions. If the exsudative turns into the proliferative phase, intraalveolar and interstitial pulmonary fibrosis may develop with atypical epithelial proliferations. The prognosis of cytostatics-induced pneumopathies depends essentially on the time when it is diagnosied.

Topics: Antineoplastic Agents; Child; Cyclophosphamide; Drug Therapy, Combination; Humans; Leukemia, Lymphoid; Lung; Male; Mercaptopurine; Methotrexate; Prognosis; Pulmonary Fibrosis

Sister chromatid exchange (SCE) frequencies were studied in peripheral lymphocytes from 16 patients with newly diagnosed acute lymphoblastic leukemia (ALL) prior to the initiation of chemotherapy. The mean SCE frequency (mean +/- SE) for these patients was 12.2 +/- 0.2 per metaphase, which was significantly higher (P less than 0.001) than the mean SCE score for 14 age-matched controls, 7.6 +/- 0.2. Five of these patients were studied again while they were receiving maintenance therapy consisting primarily of daily 6-mercaptopurine and weekly methotrexate. Their remission SCE levels remained significantly higher than controls (P less than 0.005). In addition, SCE levels were studied in 7 long-term survivors of ALL. Three of these patients had been receiving continuous maintenance therapy for at least 3 years. Their mean SCE scores were significantly greater than controls (P less than 0.005). The other 4 patients had finished their final course of chemotherapy at least 8 months prior to the time of sampling, and their mean SCE scores were not significantly different from controls (P greater than 0.10). These data indicate that untreated patients with ALL have increased SCE levels which remain elevated during periods of remission maintained with chemotherapy. However, long-term survivors of ALL who are in remission and off chemotherapy do not demonstrate significantly increased SCE frequencies.

Topics: Adolescent; Child; Child, Preschool; Crossing Over, Genetic; Female; Humans; Infant; Leukemia, Lymphoid; Lymphocytes; Male; Mercaptopurine; Metaphase; Methotrexate; Mitosis; Sister Chromatid Exchange

Topics: Adolescent; Child; Child, Preschool; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Infant; Leukemia, Lymphoid; Male; Mercaptopurine; Methotrexate

Topics: Adult; Age Factors; Antigens, Neoplasm; Antineoplastic Agents; Asparaginase; Cyclophosphamide; Doxorubicin; Drug Therapy, Combination; Humans; Leukemia, Lymphoid; Mercaptopurine; Methotrexate; Prednisolone; Prognosis; Vincristine

Serial liver function tests and percutaneous liver biopsies were performed on 21 children receiving treatment for acute lymphoblastic leukaemia (ALL). The patients received continuing chemotherapy either with daily 6-mercaptopurine and weekly methotrexate or with five-day pulses of these drugs every three weeks. Liver function tests were transiently abnormal in the majority of children, but the abnormalities bore no relationship to the histology of the liver biopsy. Mild inflammatory and fatty changes were commonly seen, and early portal fibrosis was found in three out of 16 patients biopsied at between 108-130 weeks on treatment. There was no correlation between treatment regime and results of biopsy. Three patients showed possible progression of abnormalities on repeat biopsy. The risk of development of portal fibrosis appears low after 2-3 years of continuing chemotherapy, but examination of liver histology may be indicated if more prolonged therapy is contemplated.

Topics: Adolescent; Antineoplastic Agents; Biopsy; Chemical and Drug Induced Liver Injury; Child; Humans; Leukemia, Lymphoid; Liver Diseases; Liver Function Tests; Mercaptopurine; Methotrexate

Of 31 children affected with acute lymphoblastic leukaemia the quantitative behaviour of eosinophilie granulocytes was examined in the course of the disease. Nearly all patients were treated according to a chemotherapy scheme (Memphis IV). During this therapy the eosinophils greatly diminished initially increased significantly to subnormal values and to the values of healthy persons with persisting full remission. Another significant decrease occurred during the relapse and in the pre-final stage. During each following relapse a greater diminution of bone-marrow eosinophils could be observed. Simultaneously the decrease of eosinophils led to a shift in the degree of maturation. In this connection the similar behaviour of neutrophilic and eosinophilic granulocytes of the bone-marrow must be stressed. Eventually, the lbast excrescence in the bone-marrow and its therapy cannot solely be decisive for the findings made. Relations to the lymphocytic system can be referred to.

Topics: Bone Marrow Cells; Cell Count; Child; Child, Preschool; Eosinophils; Female; Humans; Leukemia, Lymphoid; Male; Mercaptopurine; Methotrexate; Prednisone

A study of testicular histology has been made in 44 boys treated with combination chemotherapy for acute lymphoblastic leukaemia. At the time of testicular biopsy 21 boys were still receiving cytotoxic drugs and 23 had completed their chemotherapy some time earlier. Evidence of leukaemic infiltration was seen in 5 (11%), interstitial fibrosis in 24 (55%), and basement-membrane thickening in 6 (14%). The mean tubular fertility index in the 44 biopsies was 50% of that in age-matched controls, and 18 of the biopsies had a severely depressed tubular fertility index (40% or less). Three variables had a highly significant effect on the tubular fertility index: previous therapy with cyclophosphamide or cytosine arabinoside (greater than 1 g/m2) depressed the tubular fertility index, whereas with increasing time after completion of chemotherapy the tubular fertility index improved. The prognosis for fertility in these subjects is not known. Long-term surveilance is necessary.

Topics: Adolescent; Antineoplastic Agents; Asparaginase; Child; Child, Preschool; Cyclophosphamide; Cytarabine; Doxorubicin; Drug Therapy, Combination; Fertility; Humans; Leukemia, Lymphoid; Male; Mercaptopurine; Methotrexate; Prednisolone; Prognosis; Testis; Vincristine

An analysis of 66 children with ALL treated during the last 10 years shows an increase in medium survival time from 27.1 +/- 17.8 months to so far 39.3 +/- 15.1 months after the introduction of preventive CNS therapy. In the group with preventive CNS therapy both CNS relapses and hematological relapses are markedly reduced. Furthermore, in the group with preventive CNS therapy, patients initially treated with 3 drugs obviously survive longer than patients initially treated with only 2 drugs. Thus our study shows the importance of the quality of first remission for the further outcome of a patient with leukemia.

Topics: Brain Diseases; Child; Cyclophosphamide; Humans; Leukemia, Lymphoid; Life Expectancy; Mercaptopurine; Methotrexate; Methylprednisolone; Remission, Spontaneous; Vincristine

Evidence that the first human neoplasm systematically explored with chemotherapeutic treatments has apparently been cured in a palpable segment of affected patients evokes optimism for other types of cancer. The application of similar effort, similar logic, and quantitative experimental therapeutic approaches to the common cancers augurs well for cancer research and clinical medicine.

Topics: Antineoplastic Agents; Child; Daunorubicin; Drug Therapy, Combination; Follow-Up Studies; Humans; Leukemia, Lymphoid; Mercaptopurine; Methotrexate; Prednisone; Recurrence; Remission, Spontaneous; Vincristine

391 children received complex chemotherapy according to uniform treatment schedules, proposed by the Hungarian Study Group for Childhood Leukaemia, which was established in 1971. Survival among the patients showed an increasing tendency: more than 50% of patients with ALL are stille alive 3 years after the beginning of treatment. One patient is in complete remission 9 3/4 years after the establishment of the diagnosis. Two types of maintenance therapy were investigated among the patients entered for this study in 1974. "Pulses" with Vincristine-Prednisolone every second month were found to be more optimal than monthly "pulses".

Topics: Age Factors; Child; Cytarabine; Daunorubicin; Humans; Hungary; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Mercaptopurine; Prednisolone; Thioguanine; Vincristine

Topics: Adolescent; Adrenal Cortex Hormones; Asparaginase; Bacterial Infections; Child; Child, Preschool; Colistin; Cyclophosphamide; Cytarabine; Daunorubicin; Drug Therapy, Combination; Female; Humans; Infant; Injections, Spinal; Leukemia, Lymphoid; Male; Mercaptopurine; Methotrexate; Remission, Spontaneous; Skull; Vincristine

42 patients with ALL were treated according to the following protocol: induction with vincristine + prednisone (+/- L-asparaginase), CNS-prophylaxis with cranial irradiation (2400 rads) and intrathecal methotrexate, maintenance for 3 years with 6-MP 50 mg/m2/d p.o. + MTX 75-150 mg/m2/2 wk i.v. X 4, alternating in a cyclic fashion with 6-MP 50 mg/m2/d p.o. + cyclophophshamide 600 mg/m2/2 wk i.v. X 4. The observation time is 24-67 (median 49) months. The actuarial complete remission curve shows 40% continuous complete remissions at 36 months and 30% at 60 months.--The frequency and temporal distribution of typical infectious complications are presented. The incidence of varicella was comparable to that in a southgerman normal control group (5,7% per year). During treatment there were two zoster manifestations per one varicella case, the incidence of zoster being 1 case per 106 patient-months, viz 11,4% per year.

Topics: Adolescent; Asparaginase; Chickenpox; Child; Child, Preschool; Cyclophosphamide; Female; Herpes Zoster; Humans; Infant; Injections, Spinal; Leukemia, Lymphoid; Male; Mercaptopurine; Methotrexate; Prednisone; Remission, Spontaneous; Skull; Vincristine

The most important advances achieved during the past 5 years in the diagnosis and treatment of acute leukemia are presented. It is now possible to achieve complete remission in about 60% of all patients with acute myelocytic leukemia (AML) using optimal polychemotherapy. This significant advance is in part due to improved supportive measures such as transfusions and isolation etc., which are frequently necessary during the induction phase of treatment. Unfortunately, such remissions are still of relatively short duration and seldom exceed 1 year. The treatment of relapses remains less successful. The first attempts to include immunotherapy in the treatment of AML have also been rather disappointing. Today remissions are obtained in 70% of patients with acute lymphocytic leukemia (ALL) which last, on the average, almost 1 1/2 years. These results, however, do not approach those in childhood ALL. Finally, the therapeutic possibilities for the treatment of blastic crisis in chronic myelocytic leukemia (CML) are discussed.

Topics: Cytarabine; Daunorubicin; Drug Therapy, Combination; Humans; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Mercaptopurine; Prednisone; Remission, Spontaneous; Thioguanine; Vincristine

Comparative results of chemo- and chemoimmunotherapy with Soviet strain of BCG vaccine in children with acute leukemia are presented. The immunotherapeutical regimen includes 20 intracutaneous injections of 0.1 mg BCG vaccine given weekly during 5--6 months with subsequent 5--6 months intervals simultaneously with maintenance chemotherapy. In the control group children were only given conventional chemotherapy. The median duration of remission and survival in patients who had received BCG chemoimmunotherapy was 25.2 +/- 1.5 and 32.3 +/- 1.2 months respectively. In the group of patients with chemotherapy alone--13.2 +/- 0.9 and 21.8 +/- 1.1 months respectively (p less than 0.01). The best results were obtained in children who had received before BCG immunotherapy neuroleukemia prophylactic treatment.

Topics: Adolescent; Antineoplastic Agents; BCG Vaccine; Brain Neoplasms; Child; Child, Preschool; Drug Therapy, Combination; Female; Humans; Leukemia, Lymphoid; Male; Mercaptopurine; Methotrexate; Prednisolone; Remission, Spontaneous; Time Factors; Vincristine

Topics: Animals; Antineoplastic Agents; Cell Cycle; Cell Division; Cell Line; Clone Cells; Drug Interactions; Drug Therapy, Combination; Humans; Leukemia, Experimental; Leukemia, Lymphoid; Mercaptopurine; Methotrexate; Neoplasms, Hormone-Dependent; Prednisolone; Vincristine

Topics: Adolescent; Adult; Child; Daunorubicin; Drug Administration Schedule; Female; Humans; Leukemia, Lymphoid; Male; Mercaptopurine; Methotrexate; Prednisolone; Remission, Spontaneous; Time Factors; Vincristine

67 children affected with acute lympocytic leukemia were immunologically evaluated for lymphocytic markers, serum immunoglobulins and delayed hypersensitivity skin tests at the onset, in remission and after cessation of therapy. E, EA rosettes and surface Ig assayed significantly lower in leukemic children than in matched controls, except for three cases of T-cell leukemia in which E rosettes were very high. After cessation of therapy almost normal results were obtained. As for serum Ig, the only abnormal finding was that of low IgM during therapy. The skin tests with Varidase, Candidine, Mumps antigen and DNCB were not significantly different at onset and in remission. As for DNCB test, the negative responses at onset often became positive in remission, but only when the test was performed before any treatment (anamnestic-like response?). One of the three patients with T-cell leukemia relapsed after 8 months: strangely enough, no surface marker could be detected on that occasion. We could not find any relationship between various immunological tests, or between these tests and prognosis; chemotherapy proved active in suppressing cellular immunity, especially the primary cellular response.

Topics: Adolescent; Child; Child, Preschool; Humans; Hypersensitivity, Delayed; Immunoglobulins; Infant; Leukemia, Lymphoid; Mercaptopurine; Prednisone; Remission, Spontaneous; Rosette Formation; T-Lymphocytes; Vincristine

Recurrence of childhood acute lymphoblastic leukemia occurs in about 30-50% and indicates irresistable progression of the disease. While systemic (= hematologic) relapse is due to drug resistance of leukemic cells, pharmacologic barriers may be responsible for local relapses as meningeal involvement, leukemic ophthalmopathy or testicular infiltration. L-asparginase seems to be an important component of drug combinations for re-induction therapy for systemic relapse. Following reinduction therapy modification of continuation therapy is necessary. Local relapses require local treatment, i.e. radiotherapy and e.g. intrathecal drug application. Local relapse is almost always followed by hematologic relapse. Therefore, intensification of systemic therapy is also recommended. Prevention of these relapses is much more important and probably more successful than treatment. Therefore, initial therapy should include preventive measures for pharmacologic sanctuaries.

Topics: Asparaginase; Blood-Brain Barrier; Blood-Testis Barrier; Child; Child, Preschool; Cyclophosphamide; Cytarabine; Drug Resistance; Drug Therapy, Combination; Humans; Leukemia, Lymphoid; Meningoencephalitis; Mercaptopurine; Methotrexate; Neoplasm Recurrence, Local; Vincristine

A method is presented for the separation of 6-thiopurine bases and ribonucleosides, of sulphate anions and of common purine bases and oxidized purines by means of high-pressure liquid cation-exchange chromatography using a 0.18 X 100 cm column, filled with Beckman M71 resin, and eluted with 0.4M ammonium formate, pH 4.6, at a linear flow velocity of 5.2 cm/min at 50 degrees C. The method has been applied to the separation and quantitative determination of 14C-labeled 6-mercaptopurine metabolites in HClO4 extracts of L5178Y murine lymphoma cells. Distribution patterns of 14C radioactivity within the cells after a 24 h incubation period with (8-14C)-labeled 6-mercaptopurine have been established. The indentification of 6-mercaptopurine metabolites, such as 6-thioxanthosine ribonucleotide, 6-thioinosinic acid, 6-thioguanylic acid, 6-methylthioinosinic acid, and 6-thiouric acid, after the digestion of the extracts with alkaline phosphatase has been confirmed using the behaviour of each compound in enzymatic peak-shifting analyses with purine nucleoside phosphorylase and the corresponding elution volumes of 6-thiopurine bases and ribonucleosides as proofs. According to the specific radioactivity of the (8-14C)-labeled 6-mercaptopurine batch, the amounts of the various 6-mercaptopurine metabolites in about 6% of the total HClO4 extract of 1.6 . 10(8) labeled cells have quantitatively been determined as 1--130 pmol. The intracellular concentration of 6-thiopurines was determined at 1.4 . 10(-5)mol/1.

Topics: Alkaline Phosphatase; Animals; Cell Division; Cell Extracts; Cell Line; Chromatography, High Pressure Liquid; Leukemia, Lymphoid; Mercaptopurine; Mice; Purine-Nucleoside Phosphorylase

Topics: Aged; Animals; Chronic Disease; Cytarabine; DNA, Neoplasm; Humans; In Vitro Techniques; Leukemia, Lymphoid; Male; Mercaptopurine; Mice; Middle Aged; Neoplasms, Experimental; Ribonucleotides; RNA, Neoplasm

Evidence is presented that sesquiterpene lactones or ketones containing the O=CC=CH2 moiety, e.g., tenulin and helenalin, alkylate the thiol group of reduced glutathione and L-cysteine in vitro. A proposal is offered that this mechanism of action is responsible for the observed potent in vivo antitumor activity of these agents in the Ehrlich ascites and Walker 256 carcinosarcoma and to a lesser extent in the P388 leukemic screen. Inhibition of tumor growth is thought to occur due to the O=CC=CH2 system alkylating by rapid Michael addition the SH biological nucleophiles of key regulatory enzymes of nucleic acid and chromatin metabolism. This proposition is in accord with the ability of these agents to inhibit DNA synthesis and gene activity of Ehrlich ascites cells.

Topics: Animals; Antineoplastic Agents, Phytogenic; Ascitic Fluid; Carcinoma 256, Walker; Carcinoma, Ehrlich Tumor; Chromatin; Cyclopentanes; Cysteine; DNA, Neoplasm; Glutathione; Histidine; Lactones; Leukemia, Experimental; Leukemia, Lymphoid; Male; Mice; Mice, Inbred DBA; Neoplasm Proteins; Rats; Sesquiterpenes; Sesquiterpenes, Guaiane; Spectrophotometry, Ultraviolet; Time Factors

This report describes the results of a study of central nervous system (CNS) prophylaxis and combination chemotherapy for the maintenance of remission in adult acute lymphoblastic leukemia. Adults with acute lymphoblastic leukemia who achieved complete remission were treated with 2,400 rads cranial irradiation and intrathecal methotrexate for CNS prophylaxis followed by continuation systemic chemotherapy with oral methotrexate, 6-mercaptopurine and cyclophosphamide. There were no CNS relapses following treatment. One-half of the patients relapsed within 11 months, with 5 patients remaining in remission for 27+ to 31+ months. The toxicity was acceptable with no treatment-related deaths. This regimen is capable of producing long remissions in a significant proportion of adults with acute lymphoblastic leukemia and appears to be effective in reducing the incidence of CNS relapse. It has the additional advantage of ease of administration and can be largely administered in the community.

Topics: Adolescent; Adult; Brain Neoplasms; Cyclophosphamide; Female; Head; Humans; Leukemia, Lymphoid; Male; Mercaptopurine; Methotrexate; Middle Aged; Remission, Spontaneous; Spinal Cord Neoplasms

Continuation therapy using intermittent chemotherapy and BCG inoculation was commenced in 28 children with acute lymphocytic leukemia (ALL) immediately after remission induction and "CNS prophylaxis." At a median followup time of 17 months, 71% remain in total remission and 86% in bone marrow remission. Complications of the therapy were minimal. Major infections occurred on two occasions and there were no deaths in remission. Neutropenia, "minor" infections and postponement of chemotherapy occurred most often during the first three courses of treatment. There were no local or systemic BCG infections. Tuberculin sensitivity was tested in 25 patients. It was positive in 17 of 18 patients in total remission and all four patients with only CNS relapse, and was negative prior to relapse in three patients who developed bone marrow disease.

Topics: BCG Vaccine; Child; Child, Preschool; Drug Therapy, Combination; Humans; Infant; Leukemia, Lymphoid; Mercaptopurine; Methotrexate; Remission, Spontaneous; Vincristine

The incidence of amoeboid movement configuration (AMC), a cell shape suggestive of cell locomotion at the moment of fixation, has been studied in the tumour cells of bone marrow smears from leukaemia patients at the time of diagnosis. The groups of patients with CML (n = 8), ALL (n = 5) and CLL (n = 9) were small, and the incidences of AMC were close to those found in the corresponding cell lines from healthy probands. In 39 patients with AML, the incidence of AMC was higher than in the other cell lines investigated. A positive skew distribution of AMC values and a positive significant correlation between incidence of AMC were found at the time of diagnosis and subsequent survival of the patients with AML, in spite of differences in treatment. It is suggested that this positive correlation may be due to an immune reaction of the patients against their tumour cells.

Topics: Adolescent; Adult; Aged; Aminopterin; Bone Marrow; Cell Line; Cell Movement; Child, Preschool; Female; Humans; Leukemia, Lymphoid; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Middle Aged; Prednisolone; Prognosis; Vincristine

Lymphopenia induced by treatment for acute lymphoblastic leukaemia is analysed and discussed in relation to the type and incidence of infection occurring in those patients during complete remission. Blood lymphocytes can be placed into three largely independent groups: (1) those lymphocytes susceptible to long-term depletion following irradiation; (2) those lost from the blood during and for a short period after maintenance chemotherapy with methotrexate and 6-mercaptopurine; and (3) the remainder which are not depleted by irradiation or maintenance chemotherapy. The number of cells in each compartment varies from child to child and probably with age but on average is about 1.2 x 10(9)/1. for group 1, 0.7 x 10(9)/1. for group 2 and 0.4 x 10(9)/1. for group 3. Conventional lymphocyte typing crosses these barriers in that: Group 1 consists mainly of E-rosetting cells and cells which show a mitotic response to phytohaemagglutinin; Group 2 also contains E-rosetting cells but contains a major proportion of blood lymphocytes with surface immunoglobulin and essentially all antibody dependent cytotoxic lymphocyte (K-cell) activity; Group 3 comprises E-rosetting cells and a few immunoglobulin-staining cells.

Topics: Antimetabolites, Antineoplastic; Humans; Immunosuppression Therapy; Leukemia, Lymphoid; Lymphocytes; Lymphopenia; Mercaptopurine; Methotrexate; Radiation Injuries; Radiotherapy

Topics: Central Nervous System Diseases; Child; Child, Preschool; Diagnosis, Differential; Female; Humans; Immunotherapy; Injections, Spinal; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Methotrexate; Prednisolone; Remission, Spontaneous; Vincristine

This report describes a 10-year-old white boy who presented with acute lymphocytic leukemia (ALL) and several collapsed thoracolumbar vertebrae in 1965. His ALL was successfully treated, and he has been disease-free for over 10 years. He has now completely remodeled all of the collapsed vertebrae.

Topics: Bone Regeneration; Child; Cyclophosphamide; Daunorubicin; Fractures, Spontaneous; Humans; Leukemia, Lymphoid; Lumbar Vertebrae; Male; Mercaptopurine; Methotrexate; Prednisone; Thoracic Vertebrae; Vincristine

Induction chemotherapy consisting of vincristine, prednisone and L-asparaginase was given to 22 adult patients with acute lymphatic leukemia. Manintenance treatment consisted of methotrexate, 6-mercaptopurine, prednisone and vincristine. Of the 22 patients treated, 14 had a complete remission. The median remission duration was 14 months and the median survival 20 months. 8 further patients were included in an attempt to determine the significance of prognostic factors, but none of the parameters studied influence the course of disease with statistical significance. In general, younger patients and those with lower leukocyte counts at the time of diagnosis seemed to fare better.

Topics: Adult; Asparaginase; Drug Therapy, Combination; Humans; Leukemia, Lymphoid; Mercaptopurine; Methotrexate; Prednisone; Prognosis; Remission, Spontaneous; Time Factors; Vincristine

Topics: Asparaginase; Child; Child, Preschool; Cyclophosphamide; Female; Humans; Infant; Leukemia, Lymphoid; Male; Mercaptopurine; Methotrexate; Prednisolone; Skull; Vincristine

Topics: Chemical and Drug Induced Liver Injury; Child; Child, Preschool; Humans; Leukemia, Lymphoid; Liver; Liver Function Tests; Mercaptopurine; Methotrexate; Remission, Spontaneous

Topics: Adolescent; Child; Child, Preschool; Cyclophosphamide; Female; Humans; Infant; Injections, Spinal; Leukemia, Lymphoid; Male; Mercaptopurine; Methotrexate; Prednisone; Thioguanine; Vincristine

Twin girls, genetically identical, probably experienced different leukemogenic events and presented with acute lymphocytic leukemia 6 years apart. Their clinical presentations were similar, but they received significantly different therapy. The first twin died 34 months after diagnosis following multiple remissions and relapses, having received single-drug maintenance. The second twin remains free of apparent disease 60 months after diagnosis, following vincristine and prednisone induction, 6-mercaptopurine maintenance, methotrexate and prednisone reinforcement, and central nervous system treatment of occult disease. Their dissimilar clinical courses may have been due to different leukemogenic events and/or markedly different therapeutic programs.

Topics: Antineoplastic Agents; Child; Child, Preschool; Cyclophosphamide; Cytarabine; Drug Therapy, Combination; Female; Humans; Hydrocortisone; Leukemia, Lymphoid; Mercaptopurine; Methotrexate; Prednisone; Recurrence; Remission, Spontaneous; Vincristine

Eighteen (72%) of 25 evaluable and previously untreated patients with adult acute lymphoblastic leukemia entered complete remission (CR) following induction therapy with adriamycin, vincristine, and prednisone in a Southwest Oncology Group study. Remission maintenance therapy with methotrexate and 6-mercaptopurine resulted in a median duration of CR of 10.2 months. The addition of Adriamycin to prednisone and vincristine may be beneficial in slow responders or nonresponders to these two drugs and in patients with initially high peripheral blood blast counts.

Topics: Adolescent; Adult; Aged; Doxorubicin; Drug Evaluation; Drug Therapy, Combination; Female; Humans; Leukemia, Lymphoid; Male; Mercaptopurine; Methotrexate; Middle Aged; Prednisone; Remission, Spontaneous; Vincristine

Ten of 70 children (14%) with acute lymphoblastic leukemia developed severe interstitial pneumonitis within three weeks after induction of central nervous system prophylactic therapy. The clinical picture was characterized by fever, cough, progressive dyspnea, and hypoxemia with complete resolution in one to three weeks, except in one patient who died during the acute illness from respiratory failure. P. carinii organisms were found in the lung tissue of only one patient. The etiology of the pneumonitis in the other nine children was probably viral, acquired or activated during a period of lymphopenia and immunosuppression. The morbidity and potential mortality from the pneumonitis warrants early recognition by open lung biopsy and intensive supportive therapy.

Topics: Central Nervous System Diseases; Humans; Immunosuppression Therapy; Leukemia, Lymphoid; Leukocyte Count; Mercaptopurine; Methotrexate; Pneumonia, Pneumocystis; Pulmonary Fibrosis

Acute lymphoblastic leukaemias which are, at the present time, curable are those which go 01.cfhçinto remission following treatment with the combination prednisone-vincristine, in which lymphoblastic meningitis does not occur after preventive treatment of the central nervous system and which show no recurrence during maintenance chemotherapy. In order that the largest possible number of these potentially curable patients may be transformed into truly cured cases, we propose here a simple outline of treatment: induction of remission by one month of treatment with prednisone 40 mg/m2/day and vincristine 1.5 mg/m2/week, immediately followed by treatment of the central nervous system: 2 400 rads to the brain down to C2 in two weeks and an half and 6 injection (2 per week) of intrathecal methotrexate 5 mg/m2/injection and maintenance chemotherapy for two years with 6 MP, 25 to 50 mg/m2/day and parenteral methotrexate, 10 to 15 mg/m2/week, then immunotherapy with BCG, for a minimum of three years and a maximum of five.

Topics: BCG Vaccine; Daunorubicin; Drug Administration Schedule; Drug Therapy, Combination; Humans; Immunotherapy; Injections, Spinal; Leukemia, Lymphoid; Long-Term Care; Lymphocytes; Meningeal Neoplasms; Mercaptopurine; Methotrexate; Mycobacterium bovis; Prednisone; Remission, Spontaneous; Vincristine

This paper compares anti-leukaemic efficiency with toxicity to the patient of chemotherapy during and immediately after central nervous system irradiation. The drug regimen consisted of daily mercaptopurine (MP) and weekly methotrexate (MTX) at the maximum tolerated dose. Of 140 patients with acute lymphoblastic leukaemia allocated to receive this drug regimen during and after cranial irradiation, 8 died in complete remission within 6 months of the end of irradiation. Details of the nature of these deaths are given. This result led the Working Party to modify the chemotherapy scheduled for this stage in treatment. The modified chemotherapy consisted of MP at reduced dosage before and during cranial irradiation and omission of MP and MTX for 3 weeks after irradiation, during which time daily prednisolone with 2 doses of vincristine were substituted. Following that, the treatment reverted to the original schedule of daily MP and weekly MTX at maximum tolerated dose. Of 109 patients allocated to this modified regimen only one died in remission within 24 weeks after cranial irradiation. Analysis of the anti-leukaemic effect of the modified regimen showed that up to 600 days it was at least as effective as the original more intensive regimen. We conclude that there is a definite advantage in keeping chemotherapy to a minimum during and immediately following cranial prophylactic irradiation.

Topics: Brain; Child; Child, Preschool; Female; Humans; Infection Control; Leukemia, Lymphoid; Male; Mercaptopurine; Methotrexate; Remission, Spontaneous

The criteria for false positivity of the NBT test were described including absence of classical clinical signs of bacterial infection, negative blood (and, if necessary, other) cultures, and lack of response of antibacterial treatment as the basis for appreciation of positive NBT test result as false-positive. A case of acute lymphoblastic leukaemia with all the criteria being fulfilled was described.

Topics: Adult; Bacterial Infections; Cyclophosphamide; False Positive Reactions; Female; Humans; Leukemia, Lymphoid; Male; Mercaptopurine; Nitroblue Tetrazolium; Recurrence; Remission, Spontaneous; Sulfamethoxazole; Tetrazolium Salts; Trimethoprim; Vincristine

Clinical and experimental findings on possible changes of the lymphocyte function during an immunosuppressive or cytostatic therapy respectively caused investigations to be made for explaining the connections existing between the influence of cellular immunoreaction and the use of different cytostatic regimes. Earlier findings on the influence of cellular immunoreaction after adding cytostatics to cultivated cells and investigations on the influence of the lymphocyte function in dependence on cytostatic therapy were used for comparison. Transformation and mitosis rates as well as necrosis rates and the result of macrophage migration inhibition are comparable parameters for influencing the lymphocyte function in children treated with cytostatics. Antimetabolites, vincristine, asparaginase and daunomycin will have less influence on the transformation rate as an expression of an immunosuppressive effect on only those cells responding in accordance with their kinetic phase. Cyclophosphamide will inhibit the transformation reaction more significantly. Examinations in children with different therapeutic regimes reveal a certain validity of therapy after the first statistical evaluation of the clinical material.

Topics: Child; Cyclophosphamide; Drug Therapy, Combination; Humans; Leukemia, Lymphoid; Lymphocyte Activation; Mercaptopurine; Methotrexate; Vincristine

Topics: Asparaginase; Child; Cyclophosphamide; Cytosine; Daunorubicin; Doxorubicin; Drug Therapy, Combination; Hodgkin Disease; Humans; Infant; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Lymphoma; Melphalan; Mercaptopurine; Methotrexate; Neoplasms; Nitrogen Mustard Compounds; Osteosarcoma; Prednisone; Procarbazine; Prognosis; Remission, Spontaneous; Rhabdomyosarcoma; Teniposide; Thioguanine; Vincristine; Wilms Tumor

The development of an effective therapeutic regimen for acute lymphocytic leukemia (ALL) of childhood is described. By careful surveillance of toxicity and efficacy, positive modifications of treatment strategy were achieved without resorting to classically randomized trails. Teh resultant protocol utilizes vincristine-prednisone induction followed by asparaginase consolidation, intensive intermittent combination maintenance chemotherapy with adriamycin as a major component, and cranial radiotherapy plus intrathecal methotrexate for central nervous system prophylaxis. Preliminary analysis suggests that this regimen may result in prolonged continuous complete remission in at least 80% of children with ALL.

Topics: Adolescent; Adult; Antineoplastic Agents; Asparaginase; Child; Child, Preschool; Doxorubicin; Drug Therapy, Combination; Female; Humans; Infant; Leukemia, Lymphoid; Male; Mercaptopurine; Methotrexate; Prednisone; Radiotherapy, High-Energy; Remission, Spontaneous; Vincristine

Central nervous system (CNS) relapse is reported in three children with acute lymphocytic leukemia who received intermittent prophylactic CNS therapy with intrathecal methotrexate. The children were on monochemotherapy either with methotrexate or 6-mercaptopurine for 2 1/2 years. The CNS relapse occurred 2 1/2, 10 and 11 months after cessation of all chemotherapy. Irradiation and/or intensive chemotherapy including drugs as BCNU and Ara-C which are known to cross the blood-brain barrier were not given. Preventive CNS radiotherapy should be considered in all children who did not receive an adequate prophylactic CNS therapy even after long-term remission before chemotherapy is stopped.

Topics: Central Nervous System Diseases; Child, Preschool; Female; Humans; Leukemia, Lymphoid; Male; Mercaptopurine; Methotrexate; Remission, Spontaneous; Time Factors

Although these studies do not allow a definitive differentiation between the relative influence of chemotherapy and radiotherapy on mitogen-induced lymphocyte transformation, the data suggested both radiotherapy and chemotherapy can cause depression; however, radiotherapy may have a more pronounced effect. The relationship between the absolute peripheral blood lymphocyte count and phytohemagglutin and pokeweed mitogen-induced lymphocyte transformation was also analyzed. These data revealed that patients who are receiving or who have received intensive therapy may have normal peripheral absolute lymphocyte counts with impaired lymphocyte transformation. Serial studies of lymphocyte transformation were evaluated in 10 children with acute lymphoblastic leukemia who received both chemotherapy and radiotherapy.

Topics: Child; Cobalt Radioisotopes; Cytarabine; Drug Therapy, Combination; Humans; Immunity, Cellular; Leukemia, Lymphoid; Leukocyte Count; Lymphocyte Activation; Lymphocytes; Mercaptopurine; Methotrexate; Mitogens; Nitrogen Mustard Compounds; Prednisone; Remission, Spontaneous; Vincristine

In accordance with the recommendations of Pinkel, 147 children with acute lymphoblastic leukemia were treated by a combined cytostatic and radiation therapy during a joint study between May 1971 and Jan. 1, 1974. After a primary cytostatical treatment which brought about a remission of 94% of the patients within four to six weeks, the cranial irradiation was performed, depending on age, with a focal dose of 1500 up to 2400 rd in the course of three or four weeks. Simultaneously, the patients were given methotrexate intrathecally which was followed, later on, by a long-term therapy with cytostatics. By means of this combined treatment, a three-year survival was obtained in 50% (8 of 16) and a complete remission in 44% (7 of 16). The prognosis is the same for boys as for girls. A less favorable prognosis concerns the patients with an initial leukocytosisf more than 50 000 leukocytes/mm3 of blood, an age of more than ten years, and leukemic cells already demonstrable in the cerebrospinal fluid.

Topics: Acute Disease; Adolescent; Age Factors; Alopecia; Brain Neoplasms; Child; Child, Preschool; Cyclophosphamide; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Infant; Leukemia, Lymphoid; Male; Mercaptopurine; Methotrexate; Prednisone; Premedication; Prognosis; Radiotherapy; Radiotherapy Dosage; Remission, Spontaneous; Skull; Vincristine

Topics: Child; Child, Preschool; Cyclophosphamide; Humans; Leukemia, Lymphoid; Mercaptopurine; Methotrexate; Prednisone; Remission, Spontaneous; Time Factors; Vincristine; X-Rays

1. Serum IgM determinations and blast cell counts were performed at regular frequent intervals in a case of acute lymphoblastic leukemia in a child. 2. An inverse relationship tended to exist between the concentration of IgM in serum and blast cells in blood during the course of relapses and remissions. 3. High dosage immunosuppressive chemotherapy caused a marked reduction in serum IgM. 4. A relationship appears to exist between IgM and blast cells which may support the concept that impaired ability to produce antibody to leukemia antigens may be an intrinsic component of this disease.

Topics: Blastocyst; Child; Cortisone; Humans; Immunoglobulin M; Leukemia, Lymphoid; Male; Mercaptopurine

Topics: Adolescent; Adult; BCG Vaccine; Female; Humans; Injections, Intradermal; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Middle Aged; Remission, Spontaneous; Vaccination

Acute leukemia associates with pregnancy is relatively uncommon, and because of the age distribution of patients with acute leukemia the majority have had acute granulocytic leukemia. Various combinations of chemotherapeutic agents are commonly employed now to obtain maximal benefit, related to differing pharmacologic activities of single agents. The present case documents the use of multiple cytotoxic drugs in the management of acute lymphocytic leukemia, with successful delivery of a normal infant. In this patient severe anemia and potentially teratogenic drugs did not appear to affect the fetus.

Topics: Adolescent; Cyclophosphamide; Delivery, Obstetric; Drug Therapy, Combination; Female; Humans; Labor, Induced; Leukemia, Lymphoid; Mercaptopurine; Methotrexate; Prednisone; Pregnancy; Pregnancy Complications, Hematologic; Vincristine

In 87 cases of acute leukemia, leukemic and normal hematopoietic cell count in the bone marrow was serially observed, and the findings were used for evaluating the effectiveness of antileukemic agents and also for determining the grade of decrease in the marrow leukemic cell count required to start the proliferation of normal hematopoietic cells and to obtain complete remission of acute leukemia in adults.

Topics: Bone Marrow; Bone Marrow Cells; Cytarabine; Daunorubicin; Drug Therapy, Combination; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Mercaptopurine; Prednisolone; Remission, Spontaneous; Vincristine

Topics: Adolescent; Antineoplastic Agents; Brain Neoplasms; Child; Child, Preschool; Cyclophosphamide; Drug Therapy, Combination; Humans; Infant; Injections, Spinal; Leukemia, Lymphoid; Mercaptopurine; Methotrexate; Netherlands; Prednisolone; Prednisone; Vincristine

Survival and response to chemotherapy were evaluated in 84 adults with granulocytic leukemia (AGL) and 22 with acute lymphocytic leukemia (ALL). Twenty-two of the 84 patients with AGL reveived no chemotherapy (untreated group). The median survival for patients with AGL who achieved complete remission (CR) was 17.1 months, compared to 6.5 months for those who achieved partial remission (PR (p less than 0.05), 2.8 months for those who failed chemotherapy (p less than 0.01), and 2.1 months for the untreated group (p less than 0.01). The median survival for patients with ALL who achieved a CR was 18.2 months, compared to 7.3 months for those who achieved a PR and 7.0 months for those who failed chemotherapy. Of patients with AGL who reveived an adequate trial of chemotherapy, 43% achieved a CR and 16% a PR; 75% of patients with ALL achieved a CR and 13% a PR. Improved survival depends on the induction of a complete or partial remission with the use of aggressive chemotherapy.

Topics: Acute Disease; Adolescent; Adult; Aged; Child; Cyclophosphamide; Daunorubicin; Drug Therapy, Combination; Humans; Leukemia, Lymphoid; Leukemia, Myeloid; Mercaptopurine; Methotrexate; Middle Aged; Prednisone; Thioguanine; Thioinosine; Vincristine

Intensive chemotherapy in patients with leukemia produced immunosuppression. The level of immunocompetence correlates with prognosis. The immunological function of 29 children with acute lymphoblastic leukemia (ALL) in complete remission and on 2 different maintenance therapies was evaluated and compared with 16 normal children (Group A). Sixteen children (Group B) with ALL received 6 mercaptopurine (6MP) daily and methotrexate (MTX) twice a week, and 13 children (Group C) received 6MP and MTX weekly for maintenance. There was depression of both cellular immunity, measured by the number of T cells and skin tests, and humoral immunity, measured by number of B cells, primary antibody production to typhoid vaccine, and levels of immunoglobulins. However, continuous maintenance therapy (Group B) produced significantly more severe immunosuppression of cellular immunity than the intermittent therapy (Group C). Humoral immunity was equally depressed in both groups of leukemia patients, but was less altered than cellular immunity. Concomitantly, patients with intermittent maintenance chemotherapy had less hematologic depression, fewer episodes of infection, and fewer died in complete remission. Patients of both groups with higher levels of immunocompetence had better prognosis with longer duration of complete remission than patients with severe immunosuppression. Out of 6 patients with "favorable immunocompetence" only 1 relapsed at 7 months and the other 5 remain in complete remission from 8 to 31 months. Among 23 leukemic patients with "unfavorable immunocompetence," 15 relapsed and 8 remain in complete remission from 9 to 26 months.

Topics: Acute Disease; Adolescent; Antibody Formation; Child; Child, Preschool; Female; Humans; Immunosuppression Therapy; Leukemia, Lymphoid; Male; Mercaptopurine; Methotrexate; Prognosis

Topics: Cerebrospinal Fluid; Child; Cyclophosphamide; Dose-Response Relationship, Radiation; Humans; Leukemia, Lymphoid; Mercaptopurine; Methotrexate; Prednisone; Vincristine

In acute lymphoblastic leukaemia the combination prednisone-vincristine induces more than 85% complete remissions. L-asparaginase which was used in complete remissions, seemed to increase their duration. Actually the best maintenance treatment consists in the combination of 6-mercaptopurine and methotrexate interrupted by reinductions. In other respects C.N.S. prophylaxis with intrathecal methotrexate and craniospinal irradiation is necessary. The well-known prognostic factors are: age, leucocytosis, tumoral syndrome, and cytological type: 216 cases of long remission have been observed. One group of these patients was treated by old methods: this represents 0.8 to 1% of the material, while 20% were treated by recent protocols with reinductions (20%).

Topics: Antineoplastic Agents; Asparaginase; Drug Therapy, Combination; Humans; Leukemia, Lymphoid; Mercaptopurine; Methotrexate; Prednisone; Remission, Spontaneous; Vincristine

Topics: Adolescent; Anaphylaxis; Asparaginase; Child; Child, Preschool; Confusion; Daunorubicin; Female; Hallucinations; Hemorrhage; Humans; Injections, Spinal; Leukemia, Lymphoid; Lymphoma, Non-Hodgkin; Mercaptopurine; Methotrexate; Pancreatitis; Prednisolone; Retroperitoneal Space; Vinblastine; Vincristine

The influence of four different cytotoxic drugs (MTX, CYC, 6MP, and ARA-C) on T, B, and O-lymphocytes was investigated in 20 children with ALL in complete remission during cyclic remission maintenance therapy. Each of the four drugs causes a marked reduction of the absolute number of T and B cells whereas the relative number lies within the normal range with the exception of CYC, which leads to a depression of the percentage of both T and B cells. The percentage of O cells is markedly increased by CYC and slightly increased by MTX, 6MP, and ARA-C. The data are interpreted with care since the function of the immune system and especially tumor rejection depends on the interaction between the different lymphocyte subpopulations.

Topics: Adolescent; Antineoplastic Agents; B-Lymphocytes; Child; Child, Preschool; Cyclophosphamide; Cytarabine; Humans; Leukemia, Lymphoid; Leukocyte Count; Lymphocytes; Mercaptopurine; Methotrexate; Remission, Spontaneous; T-Lymphocytes

On a model of experimental pneumonia in mice caused by the L-forms of bacteria against the background of diminished immunity a study was made of the therapeutic efficacy of penicillin, lincomycin, lysozyme and gamma-globulin. Lincomycin, particularly in combination with biologically-active preparations, proved to be expedience for the treatment and prophylaxis of pneumonia caused by the mentioned bacteria; a rapid arrest of pneumonic process occurred and more animals survived. In the greater percentage of cases the use of penicillin was accompanied by generalization of the process.

Topics: Animals; gamma-Globulins; Humans; Immunosuppression Therapy; Immunosuppressive Agents; L Forms; Leukemia, Lymphoid; Lincomycin; Mercaptopurine; Mice; Muramidase; Penicillins; Pneumonia

In three patients with malignant disease HBsAg was detected in the serum at least 6 months before the development of acute hepatitis type B, which in each case followed a fulminant course to death. It is suggested that suppression of the normal immunological responses to hepatitis-B viral antigens by cytotoxic drug therapy permitted widespread infection of hepatocytes. Subsequently, upon withdrawal of these drugs, recovery of immunocompetence resulted in rapid destruction of all infected hepatocytes and massive liver damage. Screening for HBsAg before cytotoxic drug therapy, careful monitoring of liver function during its withdrawal, and prompt treatment with corticosteroids should abnormalities occur may prevent this unfortunate sequence of events.

Topics: Adult; Antineoplastic Agents; Chlorambucil; Choriocarcinoma; Cyclophosphamide; Dactinomycin; Female; Hepatitis B; Hepatitis B Antigens; Humans; Immunosuppression Therapy; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Male; Mercaptopurine; Methotrexate; Prednisolone; Pregnancy; Substance Withdrawal Syndrome; Vincristine

A malignant hepatoma occurred in a 12-year-old girl who eight years previously had developed an acute lymphoblastic leukaemia which for eight years had been in complete haematological remission. Fourteen months after the last re-induction treatment period had been discontinued, but while on methotrexate and 6-mercaptopurine maintenance, a hepatocellular liver carcinoma developed of which the patient died after a fulminating course, still in complete haematological remission. As far as is known, no direct carcinogenic effect can be ascribed to the two antimetabolites, but it must be assumed that these two drugs, taken by the patient for over seven years, led to cirrhosis of the liver whose malignant transformation was significantly influenced by the immunosuppressive effects of methotrexate and 6-mercaptopurine, given as maintenance therapy according to protocol 02 LA 64, Paris.

Topics: Carcinoma, Hepatocellular; Child; Female; Humans; Leukemia, Lymphoid; Liver Cirrhosis; Liver Neoplasms; Mercaptopurine; Methotrexate; Remission, Spontaneous; Time Factors

Topics: Acute Disease; Asparaginase; Child; Child, Preschool; Cyclophosphamide; Dactinomycin; Female; Humans; Kidney Neoplasms; Leukemia, Lymphoid; Lung Neoplasms; Mercaptopurine; Methotrexate; Neoplasm Metastasis; Prednisone; Vincristine; Wilms Tumor

Topics: Antigens, Neoplasm; Cell Migration Inhibition; Child; Humans; Immune Sera; Leukemia, Lymphoid; Leukocytes; Mercaptopurine; Methotrexate; Remission, Spontaneous

Topics: Acute Disease; Adolescent; Daunorubicin; Drug Therapy, Combination; Hodgkin Disease; Humans; Leukemia, Lymphoid; Male; Mechlorethamine; Mercaptopurine; Prednisone; Procarbazine; Remission, Spontaneous; Sulfates; Vincristine

Long-term second remissions were seen in 5/66 patients with all. Relapse was extramedullary in 2/5. Persistent, progressive marrow lymphocytosis preceded relapse in 4/5 patients and persistent marrow eosinophilia in 1/5. All 5 patients had had an unmaintained remission of at least 6 months prior to relapse, and responded the second time to drugs which were essentially the same as those used initially. We conclude that long-term second remissions may occur in all. Patients who relapse after 6 months or more of unmaintained remission should be treated with the drugs used in current initial induction regimens in hope of cure.

Topics: Adolescent; Antineoplastic Agents; Child; Child, Preschool; Cyclophosphamide; Drug Therapy, Combination; Female; Humans; Leukemia, Lymphoid; Male; Mercaptopurine; Methotrexate; Neoplasm Recurrence, Local; Prednisolone; Prednisone; Remission, Spontaneous; Vincristine

The effects of six clinically active drugs were tested against a ttansplantable leukemia in inbred strain 2 guinea pigs. Cytoxan and 6-mercaptopurine were found to elicit a therqeutic response against this leukemia based on complete tumor regression of the established tumor as well as a substantial increase in survival time. Animals dying in the untreated control and drug-treated groups revealed typical generalized lymphoblastic leukemia. However, only Cytoxan-treated animals that had relapsed exhibited central nervous system involvement originating from the arachnoid membrane. A tow-drug combination of Cytoxan and 1-(2-chloroethyl)-3(trans-4-methylcyclohexyl)-1-nitrosourea was found not only to prevent meningeal leukemia development but also to result in "curing" all animals from their leukemia. This observation was based on a complete clinical, hematological, and histopathological "remission" period up to 176 days. The administration of 1-(2-chloroethyl)-3-(trans-4-methylcyclohexyl)-1-nitrosourea alone was observed not only to control the systemic leukemia but also to prevent central nervous system involvement. No relapses occurred after the first "remission" period was achieved in the groups of animals that received 1-(2-chloroethyl)-3-(trans-4-methylcyclohexyl)-1-nitrosourea.

Topics: Animals; Antineoplastic Agents; Brain Neoplasms; Cyclohexanes; Cyclophosphamide; Drug Therapy, Combination; Guinea Pigs; Leukemia, Experimental; Leukemia, Lymphoid; Male; Meninges; Mercaptopurine; Neoplasm Transplantation; Nitrosourea Compounds; Prednisolone; Remission, Spontaneous; Vincristine

Topics: Acute Disease; Age Factors; Animals; Antineoplastic Agents; Asparaginase; Drug Therapy, Combination; Humans; Leukemia, Lymphoid; Mercaptopurine; Methotrexate; Mitosis; Neutropenia; Prednisone; Remission, Spontaneous; Vincristine

The in vitro sensitivity of leukemic cells to cytotoxic drugs was assessed in 61 cases of acute leukemia in adults, 49 of them were of the no lymphoblastic type and in the first phase of the disease. The depression of the incorporation of 14-C-thymidine and 3-H-uridine after a two hours incubation with the various cytotoxic drugs was compared with the clinical result obtained with two of them There is a significant correlation between the in vitro depression of the incorporation of 14-C-thymidine and the clinical effect of the drugs. This method, which may be utilized also in solid tumors, allows to predict with some accuracy the effect of chemotherapy, and to select between the various cytotoxic drugs. However the failure of a chemotherapy is generally related to an in vitro insensitivity of the malignant cells to almost all drugs.

Topics: Acute Disease; Adolescent; Adult; Aged; Antineoplastic Agents; Asparaginase; Carbon Radioisotopes; Cells, Cultured; Cyclophosphamide; Cytarabine; Daunorubicin; Depression, Chemical; Humans; In Vitro Techniques; Leukemia; Leukemia, Lymphoid; Mercaptopurine; Middle Aged; Monomethylhydrazine; Prednisolone; Remission, Spontaneous; Thymidine; Tritium; Uridine; Vincristine

Topics: Child; Cyclophosphamide; Humans; Leukemia, Lymphoid; Mercaptopurine; Methotrexate; Prognosis; Virus Diseases

Topics: Acute Disease; Adult; Animals; Female; Humans; Immunosuppression Therapy; Immunotherapy; Isoniazid; Jejunum; Leukemia, Lymphoid; Mercaptopurine; Prednisone; Radiography, Abdominal; Radiography, Thoracic; Strongyloides; Strongyloidiasis; Vincristine

Remission induction was assessed by clinical and cell-culture criteria for 65 patients with acute myelogenous leukemia (AML), 11 patients with chronic myelogenous leukemia (CML) in blast crisis and 19 patients with acute lymphoblastic leukemia (ALL). Cyclophosphamide, cytosine arabinoside and vincristine (CAV) therapy resulted in complete remission in 23 of 50 previously untreated patients with AML and in 3 of the 11 patients with CML. Fourteen patients with ALL responded to vincristine-prednisone induction therapy and two to induction therapy with CAV. The median duration of survival of the responding patients was 2.2 years, compared with 4 months for the patients who did not respond to treatment. Granulopoietic colony formation, assessed by assay of colony-forming units dependent on colony-stimulating activity in culture (CFU-C), was abnormal in 37 of 42 bone marrow aspirates from patients with AML before treatement. CFU-C concentration increased when leukocyte-conditioned medium (LCM) was added to the cultures; 13 cultures had normal or elevated CFU-C concentration with LCM. Marrow cells of patients with ALL or CML in blast crisis demonstrated a similar pattern. Serial studies of marrow CFU-C concentration of 31 patients with AML demonstrated a change to a normal pattern with successful remission induction. Results of this study suggest that administration of purified LCM to leukemic patients might increase granulocyte production from potential but unstimulated granulopoietic precursors. This therapy would lessen the probability of death from infection during remission induction.

Topics: Acute Disease; Adolescent; Adult; Aged; Bone Marrow; Bone Marrow Cells; Cell Division; Cells, Cultured; Clone Cells; Culture Media; Cyclophosphamide; Cytarabine; Drug Administration Schedule; Drug Therapy, Combination; Female; Granulocytes; Humans; Leukemia, Lymphoid; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukocytes; Male; Mercaptopurine; Methotrexate; Middle Aged; Prednisone; Remission, Spontaneous; Vincristine

Topics: Adolescent; Child; Child, Preschool; Cytarabine; Daunorubicin; Evaluation Studies as Topic; Female; Humans; Leukemia, Lymphoid; Male; Mercaptopurine; Methotrexate; Prednisone; Time Factors; Vincristine

A greek boy is described in whom pulmonary tuberculosis and homozygous beta-thalassemia was discovered at 4 years of age. Tuberculosis was cured after 1 year of combined tuberculostatic chemotherapy. His thalassemia only required 1-2 blood transfusions per year. Acute lymphoblastic leukemia was diagnosed in the patient at 8 years of age and treated with antileukemic combination chemotherapy and cranial irradiation. 7 months after diagnosis the boy is still in continuous complete remission under antileukemic chemotherapy without requiring blood transfusions.

Topics: Blood Transfusion; Child; Cyclophosphamide; Drug Therapy, Combination; Germany, West; Greece; Humans; Leukemia, Lymphoid; Male; Mercaptopurine; Methotrexate; Prednisone; Remission, Spontaneous; Skull; Thalassemia; Time Factors; Tuberculosis, Pulmonary; Vincristine

A 13-year-old female was on maintenance therapy for acute lymphoblastic leukemia. On three occasions she received methotrexate orally and each time this was associated with reactivation of scabies rash. The mechanisms for this phenomenon are discussed.

Topics: Adolescent; Benzyl Compounds; Cytarabine; Female; Humans; Leukemia, Lymphoid; Mercaptopurine; Methotrexate; Prednisolone; Remission, Spontaneous; Scabies; Vincristine

Topics: Cell Transformation, Neoplastic; Child; Cyclophosphamide; Humans; Leukemia, Lymphoid; Mercaptopurine; Methotrexate; Remission, Spontaneous; Time Factors

Twelve children with acute lymphocytic leukemia who had been in complete remission on continuous chemotherapy for at least 12 months, were treated with intermittent courses of chemotherapy alternating with BCG inoculation during the drug-free intervals. Measurements were made of leukocyte populations in blood and bone marrow leukemic blastogenic responses of blood lymphoid cells to phytohemmagglutinin and soluble leukemic blast cell membrane antigen. Antibody titers to a soluble leukemic blast-cell membrane-derived antigen were determined. Comparison was made with similar measurements during a second phase of intermittent chemotherapy without BCG inoculation (phase II). Two children showed bone-marrow relapse and two developed central nervous system leukemia during the study. Rises in blood and bone-marrow lymphoid cell numbers were found during both phases of the study. Blastogenic responses to phytohemagglutinin, depressed at the start of the study following at least 12 months of continuous chemotherapy, rose during intermittent chemotherapy and BCG and remained within normal ranges during phase II. Antibody titers and blastogenic responses to leukemia blast-cell membrane antigens increased in eight of twelve and six of seven children respectively during the BCG phase and were maintained during phase II. Only one child showed further increases in phase II. The combination of BCG and intermittent chemotherapy may increase leukemia-associated immunity in some patients with acute lymphocytic leukemia in remission. The separate contributions of either BCG or intermittent chemotherapy in producing this effect cannot be determined by this study.

Topics: Antibodies, Neoplasm; Antigens, Neoplasm; BCG Vaccine; Bone Marrow Cells; Cell Membrane; Child; Child, Preschool; Cyclophosphamide; Drug Therapy, Combination; Female; Humans; Immune Adherence Reaction; Immunotherapy; Leukemia, Lymphoid; Leukocyte Count; Male; Mercaptopurine; Methotrexate; Remission, Spontaneous; Skin Tests; Vincristine

Lanzkowsky, P., Shende, A., Aral, I., Saluja, G. (1975). Archives of Disease in Childhood, 50, 685. Organ irradiation and combination chemotherapy in treatment of acute lymphocytic leukaemia in children. A total of 30 consecutive children with acute lymphocytic leukaemia (ALL) were treated from June 1971 until December 1974. Remission was induced with the use of vincristine and prednisone. After induction of remission, cranial irradiation and intrathecal methotrexate were given. Then the liver, spleen, and kidney were irradiated and 6-mercaptopurine, cyclophosphamide, and methotrexate were administered during the maintenance phase. Pulsed doses of vincristine and prednisone were administered at 10- to 12-week intervals. The patients were subdivided into two groups based on their initial white blood cell (WBC) counts: a standard risk group with an initial WBC count of less than 25 000/mm3 (25 X 10(9)/1) and a high risk group with an initial WBC count greater than 25 000/mm3 (25 X 10(9)/1). Of the 30 children entered in this study one standard risk patient died in the induction phase before attaining remission. Analysis of the results is therefore based on the remaining 29 patients, 22 standard risk and 7 high risk patients, who attained complete remission. Survival rates in continuous remission were found to be 43% of the high risk group, 88% for the standard risk group, and 77% for the combined group. Analysis of the data indicates that this therapy is unsatisfactory in high risk ALL. The results to date of this therapy for standard risk are sufficiently encouraging to continue its use in this subgroup of patients.

Topics: Antineoplastic Agents; Child; Child, Preschool; Cyclophosphamide; Drug Therapy, Combination; Female; Humans; Infant; Kidney; Leukemia, Lymphoid; Leukocytes; Liver; Male; Mercaptopurine; Methotrexate; Prednisone; Spleen; Vincristine

Topics: Acute Disease; BCG Vaccine; Central Nervous System Diseases; Humans; Immunosuppression Therapy; Immunotherapy; Leukemia, Lymphoid; Leukocyte Count; Lymphocytes; Lymphopenia; Mercaptopurine; Methotrexate; Neutropenia

27 adult patients with acute lymphocytic leukemia have been analyzed. Complete remission was induced in 9 of 113 patients treated with prednisone +6-MP, 4 of 6 patients treated with prednisone + vincristine, and the one patient treated with a combination of prednisone, vincristine, 6-MP, and methotrexate. The median survival for these 20 patients was 11 months and the median duration of complete remission was 71/2 months. Two of these patients remain in complete remission at 8+ years. Our most recent regimen for remission induction, prednisone + vincristine + daunomycin, has produced complete remission in 7 of 7 patients, with a median duration of complete remission of 15 months. Three patients remain in their original complete remission from 16+ to 24+ months, and 5 of these 7 patients remain alive from 16+ to 24+ months.

Topics: Adolescent; Adult; Central Nervous System; Daunorubicin; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Leukemia, Lymphoid; Male; Mercaptopurine; Methotrexate; Middle Aged; Prednisone; Remission, Spontaneous; Vincristine

An overview is presented of the improvements in the prognosis of acute lymphocytic leukemia due to combined modality therapy. With the best available regimens, approximately 50% of these children have remained leukemia-free for 5 years or more. Because of these results, there is growing concern for the quality of survival and for the side effects of therapy. A case in point is a completely unexpected side effect in a current study. Nonleukemic leukoencephalopathy has developed in 8 of 20 children given intravenous methotrexate, 50-80 mg/m2 per week, as the sole agent following remission induction and CNS therapy. Thus, with longer remissions and survivals now commonly observed, a concerted effort is needed to minimize side effects while trying to improve further the efficacy of therapy.

Topics: Child; Cyclophosphamide; Drug Therapy, Combination; Humans; Leukemia, Lymphoid; Mercaptopurine; Methotrexate; Pneumonia, Pneumocystis; Remission, Spontaneous

Topics: Antimetabolites; Azacitidine; Azaguanine; Azauridine; Cell Membrane Permeability; Cytarabine; DNA, Neoplasm; Fluorouracil; Humans; Immunity, Cellular; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Mercaptopurine; Methotrexate; Purines; Pyrimidines

Topics: Bone Marrow Cells; Child; Cyclophosphamide; Drug Therapy, Combination; Humans; Leukemia, Lymphoid; Mercaptopurine; Methotrexate; Periodic Acid; Peroxidases; Prednisone; Prognosis; Remission, Spontaneous; Staining and Labeling; Vincristine

Topics: Bone Marrow Examination; Child; Child, Preschool; Daunorubicin; Drug Therapy, Combination; Evaluation Studies as Topic; Hematopoietic Stem Cells; Histocytochemistry; Humans; Infant; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Mercaptopurine; Methotrexate; Periodic Acid; Peroxidases; Prednisone; Prognosis; Remission, Spontaneous; Retrospective Studies; Staining and Labeling; Vincristine

Topics: Chlorambucil; Colchicine; Cyclophosphamide; Cytarabine; Dactinomycin; Daunorubicin; Doxorubicin; Drug Therapy, Combination; Fluorouracil; Humans; Leukemia, Lymphoid; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Mercaptopurine; Methotrexate; Vinblastine; Vincristine

Topics: Adolescent; Adult; Asparaginase; Child; Child, Preschool; Cytarabine; Female; Humans; Immune Sera; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Leukocytes; Lymphocyte Activation; Lymphocyte Culture Test, Mixed; Lymphocytes; Male; Mercaptopurine; Methotrexate; Middle Aged; Nitrosourea Compounds; Prednisolone; Prognosis; Thioguanine; Vincristine

Topics: Brain Neoplasms; Child; Child, Preschool; Cyclophosphamide; Cystitis; Drug Therapy, Combination; Female; Herpes Zoster; Herpesvirus 3, Human; Humans; Infant; Infections; Leukemia; Leukemia, Lymphoid; Male; Mercaptopurine; Methotrexate; Pneumonia, Viral; Prednisone; Remission, Spontaneous; Skin Diseases; Vincristine; Viral Vaccines; Virus Diseases

Topics: Adolescent; Bacterial Infections; Central Nervous System Diseases; Chicago; Child; Child, Preschool; Cyclophosphamide; Female; Follow-Up Studies; Humans; Leukemia, Lymphoid; Male; Mercaptopurine; Methotrexate; Prednisone; Vincristine

Topics: Bone Marrow; Chromatography; Humans; Leukemia, Lymphoid; Mercaptopurine; Phosphates; Ribonucleosides; Ultraviolet Rays

Topics: Anemia, Pernicious; Blood Cell Count; Bone Marrow Cells; Cytarabine; Cytoplasm; Follow-Up Studies; Hematologic Diseases; Humans; In Vitro Techniques; Leukemia, Erythroblastic, Acute; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Megakaryocytes; Mercaptopurine; Plasmacytoma; Polycythemia; Thioguanine; Thrombocytopenia

Topics: Adenocarcinoma; Adolescent; Age Factors; Autopsy; Brain Neoplasms; Cyclophosphamide; Diagnosis, Differential; Female; Humans; Immunosuppressive Agents; Leukemia, Lymphoid; Mercaptopurine; Methotrexate; Neoplasms, Multiple Primary; Pancreas; Pancreatic Neoplasms; Prednisone; Vincristine

Topics: Acute Disease; Adolescent; Adult; Age Factors; Aged; Asparaginase; Cytarabine; Daunorubicin; Drug Therapy, Combination; Female; Humans; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Methotrexate; Methylprednisolone; Middle Aged; Paresis; Prognosis; Radiotherapy Dosage; Remission, Spontaneous; Vincristine

Topics: Bone Marrow Cells; Child; Child, Preschool; Diet; Drug Therapy, Combination; Female; Humans; Leukemia, Lymphoid; Leukocyte Count; Male; Mercaptopurine; Methotrexate; Prednisolone; Prognosis; Remission, Spontaneous; Time Factors; Vincristine

Topics: Aminopterin; Antimetabolites; Azaguanine; Cytarabine; DNA, Neoplasm; Humans; Immunity, Cellular; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Mercaptopurine; Purines; Quinazolines; RNA, Neoplasm

Topics: Alkylating Agents; Animals; Antineoplastic Agents; Cyclophosphamide; Diethylamines; Disease Models, Animal; Drug Therapy, Combination; Ethylenediamines; Fluorenes; Fluorouracil; Interferon Inducers; Leukemia L1210; Leukemia, Experimental; Leukemia, Lymphoid; Male; Mercaptopurine; Methotrexate; Mice; Mice, Inbred BALB C; Mice, Inbred DBA; Prednisolone; Thioxanthenes; Vincristine

Topics: Adenine; Alkaline Phosphatase; Drug Resistance; Guanine; Humans; Hypoxanthines; Leukemia; Leukemia, Lymphoid; Lymphocytes; Mercaptopurine; Pentosyltransferases; Thioguanine

Topics: Adult; Eye Manifestations; Humans; Iris; Leukemia; Leukemia, Lymphoid; Male; Meninges; Mercaptopurine; Methotrexate; Prednisone; Remission, Spontaneous; Vincristine

Topics: Asparaginase; Child; Humans; Leukemia, Lymphoid; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Mercaptopurine; Methotrexate; Prednisone; Prognosis; Remission, Spontaneous; Vincristine

Topics: Acute Disease; Child; Child, Preschool; Drug Therapy, Combination; Humans; Leukemia, Lymphoid; Male; Mercaptopurine; Methotrexate; Prednisone; Remission, Spontaneous; Time Factors; Vincristine

Topics: Brain Neoplasms; Child; Child, Preschool; Cross Infection; Cyclophosphamide; Drug Therapy, Combination; Female; Humans; Infant; Injections, Intravenous; Leukemia; Leukemia, Lymphoid; Male; Measles; Mercaptopurine; Methotrexate; Prednisolone; Remission, Spontaneous; Spinal Neoplasms; Vincristine

Topics: Adult; Central Nervous System Diseases; Child; Daunorubicin; Drug Therapy, Combination; Humans; Leukemia, Lymphoid; Mercaptopurine; Methotrexate; Prednisone; Remission, Spontaneous; Vincristine

Topics: Antigens, Neoplasm; Cell Migration Inhibition; Child; Humans; Immune Sera; Leukemia, Lymphoid; Leukocytes; Mercaptopurine; Methods; Methotrexate; Remission, Spontaneous

Topics: Adult; Drug Therapy, Combination; Female; Humans; Leukemia, Lymphoid; Mercaptopurine; Prednisolone; Remission, Spontaneous; Time Factors

Topics: Acute Disease; Adult; Humans; Leukemia, Lymphoid; Male; Mercaptopurine; Methotrexate; Prednisolone; Skin Neoplasms

Topics: Acute Disease; Adolescent; Adult; Aged; Drug Therapy, Combination; Female; Humans; Leukemia, Erythroblastic, Acute; Leukemia, Lymphoid; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Middle Aged; Prednisolone; Prednisone

Topics: Asparaginase; Daunorubicin; Doxorubicin; Humans; Leukemia, Lymphoid; Leukemia, Myeloid; Mercaptopurine; Vincristine

Topics: Arachnoid; Asparaginase; Brain Neoplasms; Cerebrospinal Fluid; Child; Cyclophosphamide; Daunorubicin; Drug Therapy, Combination; Follow-Up Studies; Humans; Immunotherapy; Leukemia, Lymphoid; Mercaptopurine; Methotrexate; Neoplasm Metastasis; Prednisolone; Prednisone; Remission, Spontaneous; Vincristine

Phagocytosis and bacterial capacity of peripheral blood leucocytes were studied in 49 children with acute lymphoblastic leukaemia. No impairment of phagocytic ability was found, but 36% of children in relapse and 25% in remission had varying degrees of diminished intracellular killing capacity of ingested Staphylococcus aureus. Serial values in the same individual were constant irrespective of drugs used or stage of the disease. There was a highly significant positive correlation between bactericidal capacity ratio and the number of episodes of infection per patient; there was no significant correlation with death from infection.

Topics: Adolescent; Blood Bactericidal Activity; Child; Child, Preschool; Cyclophosphamide; Female; Humans; Infant; Leukemia, Lymphoid; Leukocytes; Male; Mercaptopurine; Methotrexate; Phagocytosis; Prognosis; Remission, Spontaneous; Staphylococcal Infections; Vincristine

Topics: Child; Common Cold; Hepatitis B; Humans; Influenza, Human; Leukemia, Lymphoid; Male; Mercaptopurine; Methotrexate; Mouth Diseases; Prednisone; Remission, Spontaneous; Time Factors; Ulcer; Vincristine

Topics: Agranulocytosis; Anemia, Aplastic; Anti-Bacterial Agents; Antineoplastic Agents; Asparaginase; Blood Platelets; Blood Transfusion; Cytarabine; Daunorubicin; Drug Therapy, Combination; Hemorrhage; Humans; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Leukocytes; Mercaptopurine; Methotrexate; Prednisone; Thrombocytopenia; Vincristine

Topics: Acute Disease; Asparaginase; Child, Preschool; Humans; Leukemia, Lymphoid; Male; Mercaptopurine; Pancreas; Pancreatitis; Prednisolone; Vincristine

Topics: Adolescent; Asparaginase; Blood Platelets; Blood Transfusion; Cephalosporins; Child; Child, Preschool; Drug Therapy, Combination; Female; Gentamicins; Humans; Infant; Leukemia, Lymphoid; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Methotrexate; Prednisolone; Prognosis; Radiotherapy; Remission, Spontaneous; Vincristine

Topics: Bone Marrow Examination; Child; Chromosome Aberrations; Drug Therapy, Combination; Endomyocardial Fibrosis; Eosinophilia; Heart Murmurs; Humans; Hydrocortisone; Leukemia, Lymphoid; Liver; Lymph Nodes; Male; Mercaptopurine; Methotrexate; Myocardium; Organ Size; Pneumonia, Pneumocystis; Prednisone; Recurrence; Tachycardia; Vincristine

Topics: Child, Preschool; Cyclophosphamide; DNA, Neoplasm; Female; Humans; Immunosuppressive Agents; Lectins; Leukemia, Lymphoid; Lymphocyte Activation; Lymphocytes; Lymphotoxin-alpha; Mercaptopurine; Methotrexate; Remission, Spontaneous; Time Factors

Topics: Antibody Specificity; B-Lymphocytes; Bone Marrow; Bone Marrow Cells; Child; Cyclophosphamide; Drug Therapy, Combination; Fluorescent Antibody Technique; Humans; Immune Adherence Reaction; Immune Sera; Immunoglobulin A; Immunoglobulin G; Immunoglobulin M; Leukemia, Lymphoid; Leukocyte Count; Mercaptopurine; Methotrexate; Prednisone; T-Lymphocytes; Vincristine

Topics: Age Factors; Child, Preschool; Dactinomycin; Humans; Leukemia, Lymphoid; Leukocyte Count; Mercaptopurine; Methotrexate; Models, Biological; Nitrogen Mustard Compounds; Prognosis; Regression Analysis; Remission, Spontaneous; Statistics as Topic; Time Factors

Topics: Animals; Cell Division; Cell Line; Cell Survival; Inosine; Leukemia, Experimental; Leukemia, Lymphoid; Mercaptopurine; Mice; Purine Nucleotides; Sulfides; Thioguanine; Thymidine

Topics: Animals; Antimetabolites; Cell Line; Cell Survival; Deoxyribonucleosides; Deoxyribonucleotides; DNA, Neoplasm; Drug Synergism; Drug Tolerance; Guanine Nucleotides; Guanosine; Inosine; Leukemia, Experimental; Leukemia, Lymphoid; Mercaptopurine; Mycophenolic Acid; Ribonucleotides; RNA, Neoplasm; Stimulation, Chemical; Sulfides; Sulfur Radioisotopes; Thioguanine

Topics: Acute Disease; Asparaginase; Bone Marrow Examination; Bone Neoplasms; Child, Preschool; Cyclophosphamide; Cytarabine; Daunorubicin; Humans; Leukemia, Lymphoid; Male; Mercaptopurine; Methotrexate; Prednisone; Radiography; Remission, Spontaneous; Urticaria Pigmentosa; Vincristine

Topics: Antineoplastic Agents; Asparaginase; Cyclophosphamide; Cytarabine; Daunorubicin; Doxorubicin; Drug Synergism; Humans; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Mercaptopurine; Methotrexate; Prednisone; Prognosis; Remission, Spontaneous; Thioguanine; Vincristine

Topics: Adolescent; Adult; Antineoplastic Agents; Child; Daunorubicin; Humans; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Mercaptopurine; Methotrexate; Prednisone; Remission, Spontaneous; Time Factors; Vincristine

Topics: Child; Humans; Leukemia, Lymphoid; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Mercaptopurine

Topics: Adolescent; Appendicitis; Child; Child, Preschool; Gastrointestinal Diseases; Humans; Hypersplenism; Infant; Intestinal Obstruction; Intussusception; Leukemia; Leukemia, Erythroblastic, Acute; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Mercaptopurine; Pancreatitis; Postoperative Complications; Prednisone; Thrombocytopenia; Time Factors

Topics: Acute Disease; Adolescent; Adult; Age Factors; Biopsy, Needle; Breast Neoplasms; Child; Cytarabine; Daunorubicin; Diagnosis, Differential; Female; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Menarche; Mercaptopurine; Methotrexate; Prednisolone; Sulfates; Vincristine

Topics: Administration, Oral; Adolescent; Antineoplastic Agents; Cyclophosphamide; Drug Synergism; Follow-Up Studies; Humans; Infertility, Male; Leukemia, Lymphoid; Male; Mercaptopurine; Methotrexate; Paternity; Prednisone; Remission, Spontaneous; Spermatozoa; Time Factors

Topics: Acute Disease; Adult; Child; Cyclophosphamide; Cytarabine; Humans; Hydroxyurea; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Mercaptopurine; Methotrexate; Prednisolone; Thioguanine; Vincristine

Topics: Adult; Bone Marrow Examination; Chromosome Aberrations; Chromosomes, Human, 21-22 and Y; Chromosomes, Human, 6-12 and X; Humans; Injections, Spinal; Karyotyping; Leukemia, Lymphoid; Male; Mercaptopurine; Methotrexate; Pedigree; Prednisone; Quinacrine; Skin; Vincristine

Topics: Age Factors; Child; Female; Fractures, Spontaneous; Humans; Leukemia, Lymphoid; Male; Mercaptopurine; Methotrexate; Osteoporosis; Prednisone; Radiography; Remission, Spontaneous; Spinal Diseases; Thoracic Vertebrae

Topics: Child; Female; Humans; Hypersplenism; Leukemia, Lymphoid; Leukocytes; Mercaptopurine; Methotrexate; Prednisone; Remission, Spontaneous; Splenectomy

Topics: Acute Disease; Bone Marrow Cells; Child; Cyclophosphamide; Humans; Leukemia, Lymphoid; Mercaptopurine; Methotrexate; Prednisolone; Remission, Spontaneous; Vincristine

Topics: Adult; Bone Marrow Cells; DNA; Humans; Leukemia, Lymphoid; Leukocyte Count; Lymphocytes; Male; Mercaptopurine; Mitosis; Prednisone; Spectrophotometry; Thymidine; Time Factors; Tritium

Topics: Child; Child, Preschool; Copper; Hepatomegaly; Humans; Infant; Leukemia, Lymphoid; Mercaptopurine; Methotrexate; Remission, Spontaneous; Spectrophotometry, Atomic; Splenomegaly; Zinc

Topics: Adolescent; Adult; Age Factors; Antineoplastic Agents; Bone Marrow; Digestive System; Evaluation Studies as Topic; Humans; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Liver; Mercaptopurine; Methotrexate; Middle Aged; Paresthesia; Prednisone; Prognosis; Remission, Spontaneous; Time Factors; Vincristine

Topics: Acute Disease; Female; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Methotrexate; Prednisone; Remission, Spontaneous; Vincristine

Topics: Adenine; Adolescent; Adult; Aged; Antimetabolites; Drug Resistance; Female; Guanine; Humans; Hypoxanthines; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukocytes; Male; Mercaptopurine; Mutation; Pentosyltransferases; Remission, Spontaneous; Thioguanine

Topics: Acute Disease; Child; Humans; Leukemia, Lymphoid; Mercaptopurine; Methotrexate; Prednisone; Remission, Spontaneous; Vincristine

Topics: Acute Disease; Adolescent; Age Factors; Child; Child, Preschool; Female; Humans; Infant; Leukemia, Lymphoid; Male; Mercaptopurine; Methotrexate; Remission, Spontaneous; Time Factors; Vincristine

Topics: Adolescent; Blood Cell Count; Bone Marrow Examination; Cytarabine; Eosinophilia; Female; Humans; Karyotyping; Leukemia, Lymphoid; Mercaptopurine; Mycoses; Sulfamethoxazole; Thioguanine; Trimethoprim; Vincristine

Topics: Adolescent; Adult; Aged; Child; Child, Preschool; Cytarabine; Evaluation Studies as Topic; Female; Humans; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Methotrexate; Middle Aged; Remission, Spontaneous; Time Factors; Vincristine

Topics: Acute Disease; Age Factors; Central Nervous System; Central Nervous System Diseases; Child; Cyclophosphamide; Cytarabine; Drug Therapy, Combination; Humans; Injections, Spinal; Leukemia, Lymphoid; Mercaptopurine; Methotrexate; Prednisone; Radiation Effects; Remission, Spontaneous; Time Factors; Vincristine

Topics: Acute Disease; Adolescent; Female; Gangrene; Humans; Leukemia, Lymphoid; Mercaptopurine; Methotrexate; Prednisolone; Pyoderma; Rifampin

Topics: Adolescent; Adult; Allopurinol; Bone Marrow Cells; Cell Count; Child; Child, Preschool; Culture Techniques; Cytarabine; Drug Therapy, Combination; Embryo, Mammalian; Female; Humans; Injections, Spinal; Kidney; Leukemia, Lymphoid; Male; Mercaptopurine; Methotrexate; Remission, Spontaneous; Vincristine

Topics: Acute Disease; Adult; Child; Female; Humans; Leukemia; Leukemia, Lymphoid; Mercaptopurine; Prednisolone; Recurrence; Remission, Spontaneous

Topics: Central Nervous System Diseases; Cerebrospinal Fluid; Cobalt Radioisotopes; Daunorubicin; Humans; Injections, Spinal; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Leukocyte Count; Mercaptopurine; Methotrexate; Prednisone; Radioisotope Teletherapy; Recurrence; Retrospective Studies; Vincristine

Topics: Adolescent; Adult; Age Factors; Aged; Central Nervous System Diseases; Child; Child, Preschool; Daunorubicin; Drug Therapy, Combination; Evaluation Studies as Topic; Female; Heart; Heart Diseases; Humans; Infant; Leukemia, Lymphoid; Male; Meninges; Mercaptopurine; Methotrexate; Middle Aged; Prednisone; Prognosis; Remission, Spontaneous; Sex Factors; Time Factors; Vincristine

Topics: Adrenal Cortex Hormones; Asparaginase; Cyclophosphamide; Cytarabine; Daunorubicin; Doxorubicin; Drug Therapy, Combination; Humans; Hydroxyurea; Leukemia, Lymphoid; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Mercaptopurine; Methotrexate; Thioguanine; Vincristine

Topics: Adolescent; Central Nervous System; Central Nervous System Diseases; Child; Child, Preschool; Cobalt Radioisotopes; Cyclophosphamide; Drug Therapy, Combination; Humans; Leukemia, Lymphoid; Mercaptopurine; Methotrexate; Radiation Effects

Topics: Acute Disease; Adolescent; Adult; Blood Cells; Chromosome Aberrations; Chromosome Disorders; Chromosomes; Female; Humans; Karyotyping; Leukemia; Leukemia, Erythroblastic, Acute; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Lymphatic Diseases; Male; Mercaptopurine; Middle Aged

Topics: Adolescent; Anemia, Myelophthisic; Child; Child, Preschool; Humans; Infant; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Leukocytes; Mercaptopurine; Oxidoreductases; Prednisolone; Vincristine

Topics: Child; Cyclophosphamide; Humans; Leukemia, Lymphoid; Mercaptopurine; Methotrexate; Prednisone; Remission, Spontaneous; Vincristine

Topics: Agranulocytosis; Asparaginase; Blood Cell Count; Bone Marrow Examination; Child; Cyclophosphamide; Cytarabine; Daunorubicin; Hemoglobins; Humans; Leukemia, Lymphoid; Male; Mercaptopurine; Methotrexate; Pneumonia; Prednisone; Recurrence; Vincristine

Topics: Antibody Formation; Drug Therapy, Combination; Evaluation Studies as Topic; Humans; Immunoglobulin G; Immunoglobulin M; Leukemia, Lymphoid; Lymphocytes; Meningitis; Mercaptopurine; Methotrexate; Neoplasm Recurrence, Local; Prednisone; Radiotherapy Dosage; Remission, Spontaneous; Time Factors; Vincristine

Topics: Animals; Antibody Specificity; B-Lymphocytes; Cell Membrane; Child; Cyclophosphamide; Erythrocytes; Female; Fluorescent Antibody Technique; Goats; Humans; Immune Adherence Reaction; Immune Sera; Immunoglobulin G; Leukemia, Lymphoid; Male; Mercaptopurine; Methotrexate; Sheep; T-Lymphocytes

Topics: Cytarabine; Cytological Techniques; DNA, Neoplasm; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Mercaptopurine; Methotrexate; Phosphorus

Topics: Animals; Antibody-Producing Cells; Antineoplastic Agents; Azathioprine; Cytotoxicity Tests, Immunologic; Dysgerminoma; Fluorescent Antibody Technique; Humans; Immunity; Immunoglobulins; Lectins; Leukemia, Lymphoid; Leukocyte Count; Lymphocyte Activation; Lymphocytes; Mercaptopurine; Sheep

Topics: Humans; Leukemia, Lymphoid; Mercaptopurine; Methotrexate; Neoplasm Metastasis; Nervous System Diseases; Nitrosourea Compounds; Pyrimethamine; Remission, Spontaneous; Time Factors

Topics: Antigens, Neoplasm; Bone Marrow; Bone Marrow Cells; Cell Membrane; Chromium Isotopes; Cytotoxicity Tests, Immunologic; Humans; Immunity, Cellular; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Lymphocyte Culture Test, Mixed; Mercaptopurine; Methotrexate; Prednisone; Skin Tests; Thymidine; Tritium; Vincristine

Topics: Adolescent; Adrenal Cortex Hormones; Adult; Animals; Antibodies, Viral; Asparaginase; Cyclophosphamide; Cytarabine; Fluorescent Antibody Technique; Guinea Pigs; Herpesvirus 4, Human; Humans; Hydrocortisone; Infectious Mononucleosis; Leukemia, Lymphoid; Male; Mercaptopurine; Methotrexate; Prednisone; Sheep; Vincristine

Topics: Adolescent; Adult; Asparaginase; Blood Transfusion; Bone Marrow Transplantation; Child; Cyclophosphamide; Cytarabine; Cytomegalovirus Infections; Daunorubicin; Female; Graft vs Host Reaction; Histocompatibility Testing; Humans; Immunosuppressive Agents; Leukemia, Lymphoid; Male; Mercaptopurine; Methotrexate; Prednisolone; Remission, Spontaneous; Vincristine

Topics: Adolescent; Anti-Bacterial Agents; Bone Marrow Cells; Diagnosis, Differential; Hemoglobins; Humans; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Leukocyte Count; Male; Mercaptopurine; Prednisone; Prognosis; Remission, Spontaneous; Reticulocytes

Topics: Adolescent; Antineoplastic Agents; Child; Child, Preschool; Cobalt Isotopes; Cytarabine; Female; Humans; Leukemia, Lymphoid; Lymphocyte Activation; Male; Mechlorethamine; Mercaptopurine; Methotrexate; Mitogens; Prednisone; Radiation Effects; Remission, Spontaneous; Thymidine; Time Factors; Tritium; Vincristine

Topics: Age Factors; Animals; Animals, Newborn; Antilymphocyte Serum; Cricetinae; Cyclophosphamide; Dactinomycin; Female; Immune Sera; Immunization, Passive; Leukemia, Lymphoid; Lymphocyte Transfusion; Lymphoma; Maternal-Fetal Exchange; Mercaptopurine; Methotrexate; Neoplasm Transplantation; Neoplasms, Experimental; Prednisone; Pregnancy; Spleen; Time Factors; Vincristine

Topics: Adolescent; Adult; Aged; Daunorubicin; Female; Humans; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Methotrexate; Middle Aged; Prednisone; Vincristine

Topics: Asparaginase; Child; Child, Preschool; Drug Synergism; Female; Humans; Infant; Leukemia, Lymphoid; Male; Mercaptopurine; Methotrexate; Prednisolone; Remission, Spontaneous; Vincristine

Topics: Adolescent; Adult; Asparaginase; Child; Child, Preschool; Cytarabine; Evaluation Studies as Topic; Female; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Methotrexate; Middle Aged; Remission, Spontaneous; Vincristine

Topics: Adolescent; Adult; Asparaginase; Child; Child, Preschool; Cytarabine; Drug Synergism; Female; Humans; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Prednisone; Recurrence; Thioguanine; Vincristine

Topics: Adolescent; Agranulocytosis; Anemia; Bone Marrow; Bone Marrow Cells; Child; Child, Preschool; Cyclophosphamide; Cytarabine; Daunorubicin; Drug Synergism; Female; Hemorrhage; Humans; Infant; Injections, Intravenous; Leukemia, Lymphoid; Leukemia, Myeloid; Male; Mercaptopurine; Neutrophils; Prednisolone; Thrombocytopenia; Vincristine

Topics: Adolescent; Child; Child, Preschool; Daunorubicin; Humans; Leukemia, Lymphoid; Mercaptopurine; Methotrexate; Prednisone; Prognosis; Vincristine

Topics: Central Nervous System; Child; Cobalt Isotopes; Cyclophosphamide; Humans; Injections, Spinal; Leukemia, Lymphoid; Mercaptopurine; Methotrexate; Prednisone; Radioisotope Teletherapy; Remission, Spontaneous; Vincristine

Topics: Adolescent; Cell Transformation, Neoplastic; Child; Child, Preschool; Cyclophosphamide; Humans; In Vitro Techniques; Lectins; Leukemia, Lymphoid; Leukocyte Count; Lymphocytes; Mercaptopurine; Methotrexate; Prednisone; Remission, Spontaneous; Stimulation, Chemical; Thymidine; Time Factors; Tritium; Vincristine

Topics: Adolescent; Child; Child, Preschool; Daunorubicin; Female; Humans; Infant; Leukemia, Lymphoid; Male; Mercaptopurine; Methotrexate; Prednisone; Remission, Spontaneous; Time Factors; Vincristine

Topics: Adrenal Cortex Hormones; Bone Marrow; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Monocytic, Acute; Mercaptopurine; Methotrexate; Prognosis; Remission, Spontaneous; Time Factors

Topics: Asparaginase; Central Nervous System Diseases; Child; Daunorubicin; Humans; Leukemia, Lymphoid; Mercaptopurine; Methotrexate; Prednisone; Remission, Spontaneous; Vincristine

Topics: Bone Marrow Diseases; Bone Marrow Examination; Child; Histoplasmosis; Humans; Leukemia, Lymphoid; Male; Mercaptopurine; Neoplasm Regression, Spontaneous; Prednisone; Vincristine

Topics: Acute Disease; Antineoplastic Agents; Cyclophosphamide; Drug Synergism; Humans; Immunotherapy; Leukemia, Lymphoid; Mercaptopurine; Methods; Methotrexate; Prednisone; Prognosis; Remission, Spontaneous; Vincristine

Topics: Antineoplastic Agents; Central Nervous System; Child; Cyclophosphamide; Humans; Leukemia, Lymphoid; Mercaptopurine; Methotrexate; Prednisone; Prognosis; Radiation Effects; Radiotherapy Dosage; Remission, Spontaneous; Time Factors; Vincristine

Topics: Age Factors; Antilymphocyte Serum; Antineoplastic Agents; Blood Cell Count; Busulfan; Chlorambucil; Humans; Hydroxyurea; Leukemia, Lymphoid; Leukemia, Myeloid; Mercaptopurine; Prednisone; Prognosis; Remission, Spontaneous

Topics: Acute Disease; Chickenpox; Child, Preschool; Female; Humans; Leukemia; Leukemia, Lymphoid; Mercaptopurine; Methotrexate

Topics: Adolescent; Anemia, Aplastic; Antineoplastic Agents; Central Nervous System; Child; Child, Preschool; Cyclophosphamide; Daunorubicin; Diarrhea; Drug Combinations; Female; Follow-Up Studies; Humans; Leukemia, Lymphoid; Male; Mercaptopurine; Methotrexate; Nausea; Pneumonia, Pneumocystis; Prednisone; Radiotherapy; Recurrence; Remission, Spontaneous; Stomatitis, Aphthous; Vincristine; Vomiting

Topics: Adolescent; Bone Marrow Cells; Cells, Cultured; Child; Child, Preschool; Cyclophosphamide; Female; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Lectins; Leukemia, Lymphoid; Male; Mercaptopurine; Methotrexate; Prednisone; Remission, Spontaneous; T-Lymphocytes; Thymidine; Tritium; Vincristine

Topics: Adjuvants, Immunologic; Asparaginase; Bacterial Vaccines; Cyclophosphamide; Cytarabine; Daunorubicin; Drug Synergism; Female; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Methotrexate; Mycobacterium bovis; Prednisone; Remission, Spontaneous; Thioguanine; Vincristine

Topics: Animals; Antigens, Neoplasm; Erythrocytes; Graft Rejection; Humans; Immunization; Injections, Intraperitoneal; Injections, Intravenous; Leukemia, Experimental; Leukemia, Lymphoid; Male; Mercaptopurine; Mice; Mycobacterium bovis; Neoplasm Transplantation; Procarbazine; Propionibacterium acnes; Time Factors

Topics: Adolescent; Adult; Aged; Animals; Antilymphocyte Serum; Bone Marrow Transplantation; Child; Child, Preschool; Cyclophosphamide; Cytotoxicity Tests, Immunologic; Humans; Immunity, Active; Immunization; Leukemia; Leukemia L1210; Leukemia, Experimental; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Mercaptopurine; Mice; Middle Aged; Mycobacterium bovis; Poly I-C

Topics: Adult; Aged; Anaphylaxis; Asparaginase; Asparagine; Aspartic Acid; Daunorubicin; Drug Hypersensitivity; Erwinia; Escherichia coli; Female; Half-Life; Humans; Leukemia, Lymphoid; Male; Mercaptopurine; Prednisone; Vincristine

Topics: Bone Marrow Examination; Brain Diseases; Central Nervous System Diseases; Cerebrospinal Fluid; Child; Child, Preschool; Female; Humans; Injections, Spinal; Leukemia, Lymphoid; Male; Meninges; Mercaptopurine; Methotrexate; Remission, Spontaneous; Vincristine

Topics: Adolescent; Antibodies; Antibody Formation; Antibody-Producing Cells; Bone Marrow Examination; Child; Child, Preschool; Cyclophosphamide; Female; Humans; Immunodiffusion; Immunoglobulins; Immunologic Memory; Immunosuppression Therapy; Leukemia, Lymphoid; Lymphocytes; Male; Mercaptopurine; Methotrexate; Orthomyxoviridae; Prednisone; Remission, Spontaneous; Vincristine

Topics: Adenine Nucleotides; Adult; Animals; Antibiotics, Antineoplastic; Arabinose; Carcinoma, Squamous Cell; Cricetinae; Dogs; Humans; Hypoxanthines; Kidney; Leukemia, Lymphoid; Lung Neoplasms; Lymphoma, Non-Hodgkin; Male; Mercaptopurine; Mice; Middle Aged; Neoplasms; Nucleosides; Nucleotidases; Nucleotides; Phosphorus; Rabbits; Sulfur Isotopes; Time Factors; Tritium

Topics: Aged; Female; Humans; Leukemia, Lymphoid; Mercaptopurine; Middle Aged

Topics: Carbon Isotopes; Cell Fractionation; Cell-Free System; Chromatography, Ion Exchange; Chromatography, Paper; Drug Resistance; Female; Humans; Hypoxanthines; Inosine; Inosine Monophosphate; Inosine Nucleotides; Leukemia, Lymphoid; Leukocytes; Male; Mercaptopurine; Methods; Nucleotides; Spectrophotometry; Thionucleotides

Topics: Adolescent; Adult; Child; Child, Preschool; Drug Synergism; Female; Follow-Up Studies; Humans; Injections, Spinal; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Methotrexate; Prednisone; Time Factors; Vincristine

Topics: Adolescent; Adrenal Cortex Hormones; Adult; Aged; Aminoisobutyric Acids; Asparagine; Child; Female; Hodgkin Disease; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Methotrexate; Middle Aged; Thymine; Vinblastine

Topics: Acute Disease; Africa, Southern; Asparaginase; Daunorubicin; Europe; Female; Government; History, 18th Century; Hydatidiform Mole; Immunization, Passive; International Cooperation; Leukemia, Lymphoid; Mercaptopurine; Methotrexate; Prednisone; Pregnancy; Remission, Spontaneous; Trophoblastic Neoplasms; United States; Vincristine

Topics: Adolescent; Adult; Age Factors; Aged; Amantadine; Asparaginase; BCG Vaccine; Child; Child, Preschool; Cytarabine; Humans; Hydrocortisone; Immunity, Active; Immunization, Passive; Immunotherapy; Infant; Leucovorin; Leukemia, Lymphoid; Mercaptopurine; Methotrexate; Middle Aged; Prednisone; Radiotherapy, High-Energy; Remission, Spontaneous; Vincristine

Topics: ABO Blood-Group System; Adult; Agglutination Tests; Antibodies; Antibody Formation; Cell Membrane; Humans; Immunity, Maternally-Acquired; Immunization, Passive; Immunodiffusion; Isoantigens; Leukemia, Lymphoid; Leukocytes; Male; Mercaptopurine; Nitrobenzenes; Precipitin Tests; Prednisolone

Topics: Administration, Oral; Antimetabolites; Central Nervous System; Child; Child, Preschool; Cyclophosphamide; Female; Follow-Up Studies; Humans; Injections, Intravenous; Injections, Spinal; Leukemia, Lymphoid; Male; Mercaptopurine; Methotrexate; Prednisone; Radiation Effects; Sex Factors; Time Factors; Vincristine

Topics: BCG Vaccine; Child, Preschool; Cyclophosphamide; Humans; Infant; Leukemia, Lymphoid; Mercaptopurine; Methotrexate

Topics: Adolescent; Adult; Child; Cytarabine; Female; Humans; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Methotrexate; Middle Aged; Prednisone

Topics: Adult; Child; Child, Preschool; Daunorubicin; Humans; Leukemia, Lymphoid; Mercaptopurine; Methods; Methotrexate; Prednisone; Vincristine

Topics: Adolescent; Adult; Age Factors; Aneuploidy; Bone Marrow Cells; Chromosome Aberrations; Chromosome Disorders; Chromosomes, Human, 13-15; Chromosomes, Human, 16-18; Chromosomes, Human, 21-22 and Y; Chromosomes, Human, 6-12 and X; Cyclophosphamide; Cytarabine; Female; Humans; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Middle Aged; Prednisone; Recurrence; Remission, Spontaneous; Vincristine

Topics: Cyclophosphamide; Drug Synergism; Humans; Leukemia, Lymphoid; Mercaptopurine; Methotrexate; Prednisone

Topics: Adult; Agglutination Tests; Amphotericin B; Anti-Bacterial Agents; Candida; Candidiasis; Child; Cyclophosphamide; Cytarabine; Evaluation Studies as Topic; False Negative Reactions; Female; Humans; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Methotrexate; Middle Aged; Nitrosourea Compounds; Precipitin Tests; Prednisone; Serologic Tests; Vinblastine; Vincristine

Topics: Adolescent; Adult; Antibiotics, Antineoplastic; Antineoplastic Agents; Asparaginase; Azaserine; Child; Child, Preschool; Cytarabine; Female; Glutamine; Humans; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Methotrexate; Middle Aged; Prednisolone; Remission, Spontaneous; Vincristine

Topics: Adolescent; Cyclophosphamide; Daunorubicin; Female; Humans; Leukemia, Lymphoid; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Mercaptopurine; Methotrexate; Middle Aged; Prednisolone; Vincristine

Topics: Adolescent; Adrenal Cortex Hormones; Child; Child, Preschool; Female; Follow-Up Studies; Humans; Leukemia, Lymphoid; Male; Mercaptopurine; Prognosis; Remission, Spontaneous

Topics: Acute Disease; Adolescent; Adrenal Cortex Hormones; Adult; Age Factors; Aged; Asparaginase; Child; Cyclophosphamide; Cytarabine; Daunorubicin; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Mercaptopurine; Methotrexate; Middle Aged; Remission, Spontaneous; Vincristine

Topics: Adolescent; Adult; Aged; Agranulocytosis; Allopurinol; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Blood Transfusion; Cytarabine; Humans; Leukemia; Leukemia, Erythroblastic, Acute; Leukemia, Lymphoid; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Mercaptopurine; Methotrexate; Middle Aged; Muramidase; Nausea; Prednisolone; Thrombocytopenia; Vincristine

Topics: Adolescent; Adult; Age Factors; Aged; Antineoplastic Agents; Asparaginase; Cyclophosphamide; Cytosine Nucleotides; Female; Humans; Leukemia; Leukemia, Erythroblastic, Acute; Leukemia, Lymphoid; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Leukocyte Count; Male; Mercaptopurine; Methotrexate; Middle Aged; Prednisone; Vincristine

Topics: Antineoplastic Agents; Cell Membrane Permeability; Child; Cyclophosphamide; Cytarabine; Drug Combinations; Drug Resistance; Follow-Up Studies; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Mercaptopurine; Methotrexate; Nucleotides; Prednisone; Prognosis; Vincristine

Topics: Acute Disease; Allopurinol; Bone Marrow Examination; Child; Digitalis Glycosides; Humans; Leukemia, Lymphoid; Male; Mercaptopurine; Methotrexate; Pericardium; Prednisone; Radiography; Remission, Spontaneous; Vincristine

Topics: Adolescent; Adult; Aged; Allopurinol; Anaphylaxis; Asparaginase; Blood Coagulation Disorders; Cytarabine; Daunorubicin; Drug Hypersensitivity; Female; Fever; Gastrointestinal Hemorrhage; Hallucinations; Humans; Hyperglycemia; Injections, Intravenous; Jaundice; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Liver; Male; Mercaptopurine; Methotrexate; Middle Aged; Oral Hemorrhage; Prednisone; Thioguanine; Uremia; Vincristine; Vomiting

Topics: Animals; Antibody Formation; Drug Synergism; Lectins; Leukemia, Experimental; Leukemia, Lymphoid; Male; Mercaptopurine; Mice

Topics: Adult; Antineoplastic Agents; Child; Humans; Leukemia, Lymphoid; Mercaptopurine; Methotrexate; Palliative Care; Prednisone; Prognosis; Vincristine

Topics: Adolescent; Antibiotics, Antineoplastic; Brain Diseases; Child; Child, Preschool; Cyclophosphamide; Electroencephalography; Humans; Infant; Leukemia, Lymphoid; Mercaptopurine; Methotrexate; Prednisone; Vincristine

Topics: Adolescent; Adult; Aged; Asparaginase; Azaserine; Burkitt Lymphoma; Central Nervous System Diseases; Chemical and Drug Induced Liver Injury; Child; Drug Hypersensitivity; Escherichia coli; Female; Humans; Leukemia, Lymphoid; Leukopenia; Lymphoma, Non-Hodgkin; Lymphopenia; Male; Mercaptopurine; Methotrexate; Middle Aged; Neoplasms; Pancreatitis; Thrombocytopenia

Topics: Agammaglobulinemia; Blood Protein Disorders; Blood Protein Electrophoresis; Bone Marrow Examination; Child, Preschool; Chromatography, DEAE-Cellulose; Complement System Proteins; Cyclophosphamide; Daunorubicin; Electrophoresis; Gels; Humans; Hypergammaglobulinemia; Immunodiffusion; Immunoelectrophoresis; Immunoglobulin G; Lectins; Leukemia, Lymphoid; Lymphocyte Activation; Lymphocytes; Male; Mercaptopurine; Methotrexate; Prednisone; Starch; Ultracentrifugation; Vincristine

Topics: Acute Disease; Blood Platelets; Child; Child, Preschool; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Long-Term Care; Mercaptopurine; Methotrexate; Prednisone; Vincristine

Topics: Adult; Aged; Bone Marrow Examination; Chlorambucil; Female; Hemoglobinometry; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Leukocyte Count; Male; Mercaptopurine; Prednisone; Radiation Effects; Radiography

Topics: Child; Child, Preschool; Humans; Leukemia, Lymphoid; Leukocyte Count; Leukocytosis; Mercaptopurine; Prognosis

Topics: Adult; Blood Platelets; Blood Transfusion; Child; Female; Hematopoiesis; Humans; In Vitro Techniques; Leukemia, Lymphoid; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukocyte Count; Leukocytes; Male; Mercaptopurine; Middle Aged

Topics: Adolescent; Brain Diseases; Central Nervous System; Child; Cytarabine; Diagnosis, Differential; Electroencephalography; Humans; Injections, Spinal; Leukemia, Lymphoid; Male; Mercaptopurine; Methotrexate; Prednisone

Topics: Central Nervous System Diseases; Cerebrospinal Fluid; Cerebrospinal Fluid Proteins; Child; Child, Preschool; Cyclophosphamide; Female; Humans; Injections, Spinal; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Leukocyte Count; Leukocytes; Male; Mercaptopurine; Methotrexate; Prednisone; Spinal Puncture; Vincristine

Topics: Adolescent; Adult; Aged; Child; Daunorubicin; Female; Humans; Injections, Intravenous; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Middle Aged

Topics: Adolescent; Brain Neoplasms; Child; Child, Preschool; Cyclophosphamide; Female; Humans; Infant; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Methotrexate; Neurologic Manifestations; Prednisone; Prognosis; Vincristine

Topics: Bone Marrow Examination; Chromosome Aberrations; Humans; Karyotyping; Leukemia, Lymphoid; Male; Mercaptopurine; Middle Aged; Prednisone; Radiation Injuries

Topics: Animals; Antineoplastic Agents; Asparaginase; Blood Platelets; Bone Marrow Cells; Cyclophosphamide; Cytarabine; Daunorubicin; Disease Models, Animal; Drug Synergism; Hemorrhage; Humans; Infections; Leukemia L1210; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Mercaptopurine; Methotrexate; Mice; Prednisone; Prognosis; Thrombocytopenia; Vincristine

Topics: Acute Disease; Child, Preschool; Humans; Hypertrophy; Kidney Diseases; Kidney Glomerulus; Kidney Tubules; Leukemia, Lymphoid; Male; Mercaptopurine; Methotrexate; Prednisone

Topics: Adolescent; Animals; Antineoplastic Agents; Asparaginase; Bone Marrow; Bone Marrow Cells; Child; Cytarabine; Daunorubicin; Disease Models, Animal; Humans; Leukemia, Lymphoid; Leukemia, Myeloid; Mercaptopurine; Methotrexate; Mice; Remission, Spontaneous; Vincristine

Topics: Acute Disease; Adolescent; Adult; Antibiotics, Antineoplastic; Antilymphocyte Serum; Antineoplastic Agents; Asparaginase; Child; Child, Preschool; Cyclophosphamide; Cytarabine; Drug Synergism; Female; Humans; Immunotherapy; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Methotrexate; Prednisone; Vincristine

Topics: Child; Hepatitis A; Humans; Leukemia, Lymphoid; Male; Mercaptopurine; Methotrexate

Topics: Adrenal Cortex Hormones; Adrenal Gland Neoplasms; Antineoplastic Agents; Bone Neoplasms; Bone Resorption; Child, Preschool; Cyclophosphamide; Diagnosis, Differential; Diagnostic Errors; Femoral Neoplasms; Ganglioneuroma; Humans; Leukemia, Lymphoid; Male; Mercaptopurine; Methotrexate; Neoplasm Metastasis; Neoplastic Cells, Circulating; Norepinephrine; Radiography; Splenic Neoplasms; Vincristine

Topics: Acute Disease; Antibiotics, Antineoplastic; Bone Marrow Examination; Child; Cytarabine; Humans; Leukemia; Leukemia, Lymphoid; Leukocytosis; Mercaptopurine; Methotrexate; Prednisone; Prognosis; Recurrence; Vincristine

Topics: Adolescent; Angioedema; Daunorubicin; Drug Hypersensitivity; Female; Humans; Leukemia, Lymphoid; Mercaptopurine; Methotrexate; Prednisone; Remission, Spontaneous; Urticaria; Vincristine

Topics: Adjuvants, Immunologic; Adolescent; Adult; Animals; BCG Vaccine; Child; Child, Preschool; Cyclophosphamide; Drug Therapy, Combination; Female; Humans; Immunotherapy; Leukemia L1210; Leukemia, Experimental; Leukemia, Lymphoid; Lymphocyte Transfusion; Mercaptopurine; Methotrexate; Mice; Middle Aged; Neoplasm Transplantation; Prednisone; Radiation Effects; Transplantation, Homologous; Vincristine

Topics: Adrenal Cortex Hormones; Child; Child, Preschool; Daunorubicin; Female; Humans; Infant; Leukemia, Lymphoid; Male; Mercaptopurine; Vincristine

Topics: Animals; Cytosine; Leukemia; Leukemia, Experimental; Leukemia, Lymphoid; Mercaptopurine; Mice; Thymine

Topics: Acute Disease; Adult; Antineoplastic Agents; Child; Cyclophosphamide; Cytarabine; Daunorubicin; Humans; Leukemia; Leukemia, Lymphoid; Mercaptopurine; Methotrexate; Nitroso Compounds; Prednisone; Urea; Vincristine

Topics: Acetamides; Amino Acids; Animals; Antibiotics, Antineoplastic; Antineoplastic Agents; Asparaginase; Azaserine; Azo Compounds; Dactinomycin; Drug Synergism; Female; Leukemia, Experimental; Leukemia, Lymphoid; Male; Mercaptopurine; Mice; Neoplasm Transplantation; Prednisone; Pyrroles; Ribose

Topics: Adolescent; Adult; Female; Humans; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Leukocyte Count; Male; Mercaptopurine; Methods; Middle Aged

Topics: Adolescent; Adult; Aneuploidy; Blood Cells; Bone Marrow Cells; Bone Marrow Examination; Child; Child, Preschool; Chromosome Aberrations; Chromosome Disorders; Down Syndrome; Female; Humans; Infant; Karyotyping; Leukemia, Lymphoid; Male; Mercaptopurine; Methotrexate; Middle Aged; Prednisone; Vincristine

Topics: Adolescent; Adult; Aged; Child; Child, Preschool; Female; Humans; Infant; Leukemia; Leukemia, Lymphoid; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Methotrexate; Middle Aged; Prednisolone; Prognosis

Topics: Aminopterin; Attitude of Health Personnel; Blood Transfusion; Bone Marrow Transplantation; Death; Hodgkin Disease; Humans; Leukemia, Lymphoid; Mercaptopurine; Physician-Patient Relations; Prednisone; Terminal Care; Vincristine

Topics: Acetazolamide; Acute Kidney Injury; Adult; Allopurinol; Anuria; Bicarbonates; Blood Gas Analysis; Blood Urea Nitrogen; Carbon Dioxide; Cystoscopy; Electroencephalography; Eye Manifestations; Female; Humans; Leukemia, Lymphoid; Leukocytosis; Mannitol; Mercaptopurine; Methotrexate; Peritoneal Dialysis; Prednisone; Splenomegaly; Thrombocytopenia; Uric Acid; Urinary Catheterization; Vincristine; Water-Electrolyte Balance

Topics: Chronic Disease; Cyclophosphamide; Deoxyuridine; DNA; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukocyte Count; Leukocytes; Ligases; Mercaptopurine; Methotrexate; Nucleosides; Nucleotides; Phosphotransferases; Tetrahydrofolate Dehydrogenase; Thymidine Kinase

Topics: Antigens; Blood Cell Count; Blood Proteins; Child; Child, Preschool; Humans; Hypersensitivity, Delayed; Immunity, Maternally-Acquired; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Leukocytes; Mercaptopurine; Plasmapheresis; Skin Tests

Topics: Blood Transfusion; Humans; Leukemia, Lymphoid; Mercaptopurine; Methotrexate; Prednisone; Vincristine

Topics: Adolescent; Adult; Bone Diseases; Bone Marrow; Bone Marrow Cells; Child; Female; Gallbladder Diseases; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Male; Mercaptopurine; Middle Aged; Myocardium; Pancreatic Diseases; Pericardial Effusion; Prednisone; Splenic Diseases; Time Factors; Vincristine

Topics: Adolescent; Adult; Age Factors; Aged; Bone Marrow; Bone Marrow Examination; Female; Humans; Leukemia, Erythroblastic, Acute; Leukemia, Lymphoid; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Leukocyte Count; Longevity; Male; Mercaptopurine; Middle Aged; Prednisone; Prognosis; Sex Factors; Vincristine

Topics: Acute Disease; Adolescent; Adult; Aged; Blood; Extracorporeal Circulation; Female; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Leukocyte Count; Male; Mercaptopurine; Middle Aged; Radiation Effects; Strontium Isotopes

Topics: Adolescent; Adult; Age Factors; Aminopterin; Blood Cell Count; Blood Cells; Child; Cyclophosphamide; Female; Humans; Leukemia, Lymphoid; Male; Mercaptopurine; Methotrexate; Prednisolone; Vincristine

Topics: Adult; Aged; Blood Platelet Disorders; Blood Platelets; Busulfan; Female; Humans; Leukemia, Lymphoid; Leukemia, Myeloid; Male; Megakaryocytes; Mercaptopurine; Middle Aged; Prednisolone

Topics: Antineoplastic Agents; Asparaginase; Burkitt Lymphoma; Choriocarcinoma; Cyclophosphamide; Cytarabine; Dactinomycin; Daunorubicin; Female; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Melphalan; Mercaptopurine; Methotrexate; Prednisone; Pregnancy; Vincristine; Wilms Tumor

Topics: Acute Disease; Antineoplastic Agents; Asparaginase; Chronic Disease; Cyclophosphamide; Daunorubicin; Humans; Leukemia, Lymphoid; Leukemia, Myeloid; Mercaptopurine; Methotrexate; Prednisone; Vincristine

Topics: Antibody Formation; Antineoplastic Agents; Cyclophosphamide; Cytosine; Humans; Immunotherapy; Isoantibodies; Leukemia, Lymphoid; Mercaptopurine; Methotrexate; Mycobacterium bovis; Prednisone; Prognosis; Vincristine

Topics: Adolescent; Adult; Aged; Bone Marrow Examination; Chromosome Aberrations; Female; Humans; Karyotyping; Leukemia; Leukemia, Lymphoid; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Middle Aged; Mosaicism; Nitrogen Mustard Compounds; Penicillins; Prednisolone; Streptomycin; Vitamins

Topics: Antineoplastic Agents; Hematologic Diseases; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Mercaptopurine; Methotrexate; Multiple Myeloma; Polycythemia Vera; Prednisone; Vincristine; Waldenstrom Macroglobulinemia

Topics: Adolescent; Antineoplastic Agents; Central Nervous System Diseases; Child; Child, Preschool; Cyclophosphamide; Female; Humans; Infant; Leukemia, Lymphoid; Male; Mercaptopurine; Methotrexate; Prednisone; Vincristine

Topics: Blood Cell Count; Child; Child, Preschool; Chlorambucil; Cyclophosphamide; Female; Humans; Leukemia; Leukemia, Lymphoid; Liver; Male; Mercaptopurine; Methotrexate; Organ Size; Prednisone; Prognosis; Spleen; Triethylenemelamine; Vincristine

Topics: Anti-Bacterial Agents; Diabetes Complications; Humans; Leukemia, Lymphoid; Male; Meningitis, Listeria; Mercaptopurine; Middle Aged

Topics: Child; Cyclophosphamide; Humans; Leukemia, Lymphoid; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Mercaptopurine; Methotrexate; Prednisolone; Vincristine

Topics: Bone Marrow; Child; Child, Preschool; Humans; Infant; Leukemia, Lymphoid; Leukemia, Myeloid; Mercaptopurine; Methotrexate; Prednisone; Vincristine

Topics: Adolescent; Adult; Age Factors; Aged; Antineoplastic Agents; Burkitt Lymphoma; Child; Child, Preschool; Cytarabine; Daunorubicin; Female; Humans; Infant; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Methotrexate; Middle Aged; Prednisone; Prognosis; Thioguanine; Time Factors; Vincristine

Topics: Asparaginase; Busulfan; Chlorambucil; Cyclophosphamide; Cytarabine; Humans; Hydroxyurea; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Mercaptopurine; Methotrexate; Pipobroman; Prednisolone; Vincristine

Topics: Blood Cell Count; Bone Marrow; Child; Child, Preschool; Female; Humans; Leukemia, Lymphoid; Mercaptopurine; Paramethasone

Topics: Age Factors; Antineoplastic Agents; Cyclophosphamide; Female; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Methotrexate; Paramethasone; Prognosis; Sex Factors; Vincristine

Topics: Biopsy; Blood Cell Count; Blood Cells; Bone Marrow; Bone Marrow Cells; Chromosome Aberrations; Chromosome Disorders; Cytogenetics; Female; Humans; Infant, Newborn; Karyotyping; Leukemia; Leukemia, Lymphoid; Liver; Mercaptopurine; Prednisone; Vincristine

Topics: Acute Disease; Adult; Child, Preschool; Cyclophosphamide; Daunorubicin; Humans; Leukemia, Lymphoid; Mercaptopurine; Methotrexate; Prednisone; Vincristine

Topics: Adult; Aged; Anti-Bacterial Agents; Antineoplastic Agents; Child; Female; Humans; Leukemia, Lymphoid; Lymphoma, Non-Hodgkin; Male; Mercaptopurine; Methotrexate; Middle Aged; Prednisolone

Topics: Adolescent; Bone Marrow Cells; Bone Marrow Examination; Child, Preschool; Chromosome Aberrations; DNA; Humans; Leukemia, Lymphoid; Leukocytes; Male; Mercaptopurine; Middle Aged

Topics: Antimetabolites; Biopsy; Chemical and Drug Induced Liver Injury; Child; Esophageal and Gastric Varices; Female; Gastrointestinal Hemorrhage; Humans; Hypersplenism; Hypertension, Portal; Leukemia, Lymphoid; Liver; Liver Diseases; Mercaptopurine

The therapy of acute leukemia has improved rapidly in the last two decades. Using available therapeutic agents, complete clinical and hematological remission can be achieved regularly in children with acute lymphocytic leukemia. The choice of chemotherapeutic agent, management of complications of hemorrhage and infection, and recognition of prognostic factors are important for the induction of a hematological remission. While patients in complete hematological remission are free of evidence of disease they still have residual leukemic cells, but in our present state of knowledge and with available techniques, we are unable to detect these. For this reason it is important to treat patients while in remission. The importance of dosage schedule for remission maintenance chemotherapy is stressed.In patients studied to date, regardless of the treatment used, the disease has recurred eventually. Available therapeutic agents are highly effective and highly selective, but they still fall short of providing ideal control of the disease. The continuing search for new chemotherapeutic agents is aided by the knowledge gained and techniques developed with current agents.

Topics: Adult; Anti-Bacterial Agents; Child; Cyclophosphamide; Hemorrhage; Humans; Infections; Leukemia, Lymphoid; Mercaptopurine; Methotrexate; Prednisone; Prognosis; Uric Acid; Vincristine

Topics: Breast Neoplasms; Child; Child, Preschool; Follow-Up Studies; Humans; Leukemia, Lymphoid; Mercaptopurine; Prognosis

Topics: Adolescent; Adult; Aged; Anemia, Aplastic; Antibiotics, Antineoplastic; Bone Marrow Examination; Child; Child, Preschool; Cyclophosphamide; Drug Synergism; Female; Humans; Infections; Leukemia, Lymphoid; Male; Mercaptopurine; Methotrexate; Middle Aged; Patient Isolators; Prednisone; Vincristine

Topics: Adult; Antibiotics, Antineoplastic; Child; Humans; Leukemia, Lymphoid; Mercaptopurine; Methotrexate; Prednisone; Vincristine

Topics: Adult; Antibiotics, Antineoplastic; Azathioprine; Child; Child, Preschool; Cyclophosphamide; Humans; Leukemia, Lymphoid; Mercaptopurine; Middle Aged; Vincristine

Topics: Adolescent; Bone Marrow Examination; Child; Child, Preschool; Humans; Leukemia; Leukemia, Lymphoid; Lymphoma, Non-Hodgkin; Mercaptopurine; Methotrexate; Prednisone

Topics: Child; Child, Preschool; Cyclophosphamide; Female; Humans; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Methotrexate; Prednisone

Topics: Blood Cell Count; Cytarabine; DNA; Humans; In Vitro Techniques; Injections, Intravenous; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Lymphoma, Non-Hodgkin; Mercaptopurine; Multiple Myeloma; Prednisone; RNA; Tritium; Uridine; Vincristine

Topics: Basophils; Blood Cell Count; Blood Platelets; Child; Eosinophils; Hemoglobinometry; Humans; Infectious Mononucleosis; Leukemia, Lymphoid; Leukocyte Count; Lymphocytes; Male; Mercaptopurine; Monocytes; Neutrophils; Prednisone

Topics: Acute Disease; Adrenal Cortex Hormones; Adult; Antineoplastic Agents; Child; Child, Preschool; Cyclophosphamide; Cytarabine; Daunorubicin; Female; Humans; Leukemia; Leukemia, Erythroblastic, Acute; Leukemia, Lymphoid; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Methotrexate; Middle Aged; Thrombocythemia, Essential; Vincristine

Topics: Antineoplastic Agents; Cyclophosphamide; Cytarabine; Daunorubicin; Humans; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Mercaptopurine; Methotrexate; Nitroso Compounds; Prednisone; Urea; Vincristine

Topics: Cyclophosphamide; Follow-Up Studies; Infusions, Parenteral; Leukemia, Lymphoid; Mercaptopurine; Methotrexate; Nitroso Compounds; Prednisone; Tablets; Urea; Vincristine

Topics: Adolescent; Child; Child, Preschool; Humans; Leukemia, Lymphoid; Mercaptopurine; Methotrexate; Prednisolone; Prednisone; Vincristine

Topics: Antineoplastic Agents; Asparaginase; Burkitt Lymphoma; Cyclophosphamide; Cytarabine; Daunorubicin; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Mercaptopurine; Methotrexate; Nitroso Compounds; Prednisone; Urea; Vincristine

Topics: Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Mercaptopurine; Methotrexate; Prednisolone

Topics: Antineoplastic Agents; Bone Marrow; Bone Marrow Cells; Cell Nucleus; Child; Child, Preschool; DNA; Erythropoiesis; Female; Humans; Leukemia, Lymphoid; Male; Mercaptopurine; Methotrexate; Vincristine

Topics: Bone Marrow Examination; Child; Child, Preschool; Cyclophosphamide; Densitometry; DNA, Neoplasm; Female; Histocytochemistry; Humans; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Methotrexate; Photometry; Prednisone; Vincristine

Topics: Adolescent; Antineoplastic Agents; Child; Drug Synergism; Female; Humans; Leukemia, Lymphoid; Male; Mercaptopurine; Methods; Methotrexate; Prednisone; Vincristine

Topics: Adult; Aminopterin; Antineoplastic Agents; Child; Cyclophosphamide; Daunorubicin; Humans; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Mercaptopurine; Methotrexate; Prednisone; Vincristine

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Biopsy; Blood Protein Electrophoresis; Blood Sedimentation; Blood Transfusion; Busulfan; Congo; Female; gamma-Globulins; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Lymphoma; Male; Mercaptopurine; Middle Aged; Prednisone

Topics: Adolescent; Adult; Alkaloids; Antineoplastic Agents; Azathioprine; Azirines; Child; Child, Preschool; Cyclophosphamide; Female; Humans; Injections, Intravenous; Leukemia, Lymphoid; Male; Mercaptopurine; Methotrexate; Prednisone; Vincristine

Topics: Child; Child, Preschool; Humans; Infant; Leukemia, Lymphoid; Leukemia, Myeloid; Mercaptopurine; Methotrexate; Prednisone; Vincristine

Topics: Formates; Humans; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Leukocytes; Leukopenia; Mercaptopurine; Nucleic Acids; Purines; Thymine

Topics: Antineoplastic Agents; Busulfan; Cyclophosphamide; Female; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Lymphoma; Lymphoma, Non-Hodgkin; Male; Mercaptopurine; Methotrexate; Prednisone; Vincristine

Topics: Adrenal Cortex Hormones; Adult; Antimetabolites; Antineoplastic Agents; Blood Transfusion; Child; Hodgkin Disease; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Mercaptopurine; Methotrexate; Plasmacytoma; Prednisone; Vincristine

Topics: Adolescent; Adult; Folic Acid Antagonists; Follow-Up Studies; Humans; Leukemia; Leukemia, Lymphoid; Mercaptopurine; Mortality; Steroids

Topics: Cerebrospinal Fluid; Diagnosis, Differential; Female; Humans; Hypercalcemia; Leukemia, Lymphoid; Mercaptopurine; Methotrexate; Middle Aged; Neurologic Manifestations; Prednisone

Topics: Bone Marrow Cells; Drug Therapy; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Mercaptopurine; Methotrexate; Prognosis; Statistics as Topic; Toxicology

Topics: Adolescent; Adrenal Cortex Hormones; Deafness; Drug Therapy; Leukemia; Leukemia, Lymphoid; Mercaptopurine; Neoplasms; Precursor Cell Lymphoblastic Leukemia-Lymphoma

Topics: Biomedical Research; Biometry; Blood Cell Count; Leukemia; Leukemia, Lymphoid; Lymphocytes; Mathematics; Mercaptopurine; Methotrexate; Neoplasms; Therapeutics

Topics: Alkylating Agents; Aminopterin; Busulfan; Hodgkin Disease; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Lymphoma; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Mechlorethamine; Mercaptopurine; Methotrexate; Multiple Myeloma; Neoplasms; Pathology; Primary Myelofibrosis; Sarcoma; Triethylenemelamine; Tuberculosis; Tuberculosis, Pulmonary; Urethane

Topics: Adolescent; Adrenal Cortex Hormones; Child; Drug Therapy; Geriatrics; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Lymphocytes; Mercaptopurine; Microscopy, Electron, Scanning Transmission

Topics: Antineoplastic Agents; Bone Marrow Cells; Drug Therapy; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Mercaptopurine; Methotrexate; Pathology; Prednisone; Toxicology; Vincristine

In the United States, the Acute Leukemia Task Force has been studying ways to achieve chemical control over the acute leukemias. It was found that L1210 mouse leukemia is an excellent predictive model for childhood acute leukemia. Examination of the kinetics of cell generation led to the conclusions that a single cell could multiply to a lethal number of cells in a relatively short time, and that therapy must destroy every cell. Extension of these hypotheses to childhood leukemia has permitted estimates of generation time of human leukemic cells; the size of the leukemic cell population at clinical relapse and the fractional destruction of cells by individual drugs. By the use of combinations of antileukemic drugs complete cell destruction has been approached in a few patients with early leukemia.

Topics: Animals; Antineoplastic Agents; Child; Child, Preschool; Cyclophosphamide; Drug Synergism; Humans; Leukemia, Lymphoid; Leukemia, Myeloid; Mercaptopurine; Methotrexate; Mice; Vincristine

Topics: Adolescent; Adult; Aldehydes; Blood Cell Count; Bone Marrow; Cerebrospinal Fluid; Female; Fibrinogen; Humans; Leukemia, Lymphoid; Leukemia, Myeloid; Male; Mercaptopurine; Methotrexate; Middle Aged; Vincristine

Topics: Adult; Blood Transfusion; Child; Child, Preschool; Female; Humans; Leukemia, Lymphoid; Leukemia, Myeloid; Male; Mercaptopurine; Methotrexate; Middle Aged; Prednisone; Prognosis

Topics: Adenine; Animals; Guanine; Humans; Hypoxanthines; In Vitro Techniques; Leukemia, Lymphoid; Leukemia, Myeloid; Mercaptopurine; Mice; Nucleotidyltransferases

Topics: Adolescent; Adult; Glucose; Glycolysis; Humans; Leukemia, Lymphoid; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukocytes; Mercaptopurine; Middle Aged; Oxygen

Topics: Anilides; Child; Child, Preschool; Cyclophosphamide; Female; Humans; Leucovorin; Leukemia, Lymphoid; Leukemia, Myeloid; Male; Mercaptopurine; Methotrexate; Prednisone; Urethane; Vincristine

Topics: Adolescent; Aminopterin; Animals; Azaserine; Child; Female; Humans; In Vitro Techniques; Leukemia; Leukemia, Lymphoid; Male; Mercaptopurine; Mice; Microscopy, Electron; Prednisolone; Rats; Retroviridae

Topics: Aneuploidy; Bone Marrow Examination; Child; Chromosome Aberrations; Chromosome Disorders; Chromosomes; Cyclophosphamide; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Mercaptopurine; Methotrexate; Microscopy, Electron, Scanning Transmission; Neoplasms; Pathology; Prednisone

Topics: Adolescent; Antineoplastic Agents; Blood; Child; Complement System Proteins; Cyclophosphamide; Humans; Leukemia; Leukemia, Lymphoid; Mercaptopurine; Methotrexate; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prednisone; Serologic Tests; Spectrophotometry; Thioguanine

Topics: Acute Disease; Female; Geriatrics; Humans; Leukemia; Leukemia, Lymphoid; Mercaptopurine; Pregnancy; Pregnancy Complications; Pregnancy Complications, Hematologic

Topics: Clinical Enzyme Tests; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Leukocyte Count; Mercaptopurine; Metabolism; Phosphotransferases; Pyrophosphatases

Topics: Adrenal Cortex Hormones; Chlorambucil; Cyclophosphamide; Dermatitis, Exfoliative; Genetic Diseases, X-Linked; Geriatrics; Hodgkin Disease; Leukemia; Leukemia, Hairy Cell; Leukemia, Lymphoid; Lymphatic Diseases; Lymphoma; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Mercaptopurine; Methotrexate; Mycosis Fungoides; Neoplasms; Pathology; Peptide Nucleic Acids; Physiology; Sarcoma; Severe Combined Immunodeficiency

Topics: Antineoplastic Agents; Blood Platelets; Busulfan; Chlorambucil; Factor Analysis, Statistical; Hemoglobinometry; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid; Leukocyte Count; Mercaptopurine; Phosphorus Isotopes; Toxicology; Triethylenemelamine

Topics: Anemia, Sickle Cell; Eosinophilia; Erythrocytes; Humans; Kwashiorkor; Leukemia; Leukemia, Lymphoid; Leukocytes; Mercaptopurine; Methotrexate; Oxidation-Reduction; Polycythemia Vera; Prednisolone; Purpura; Purpura, Thrombocytopenic; Reticulocytes; Thalassemia

Topics: Anemia; Anemia, Hemolytic; Betamethasone; Chlorambucil; Dexamethasone; Geriatrics; Humans; Leukemia; Leukemia, Lymphoid; Lymphoma; Lymphoma, Non-Hodgkin; Mechlorethamine; Mercaptopurine; Methylprednisolone; Pharmacology; Prednisone; Radiotherapy; Thrombocytopenia; Triamcinolone

Topics: Adolescent; Busulfan; Cyclophosphamide; Geriatrics; Leukemia; Leukemia, Lymphoid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid; Mercaptopurine; Nitrogen Mustard Compounds; Phenothiazines; Toxicology; Uracil Mustard

Topics: Aminopterin; Animals; Antineoplastic Agents; Busulfan; Chlorambucil; Cyclophosphamide; Geriatrics; Histological Techniques; Hydrocortisone; Leukemia; Leukemia, Lymphoid; Leukocytosis; Mercaptopurine; Methotrexate; Mice; Polycythemia Vera; Purines; Research; Tissue Culture Techniques

Topics: Adolescent; Anti-Bacterial Agents; Antibiotics, Antitubercular; Antitubercular Agents; Blood Transfusion; Bone Marrow Examination; Central Nervous System Diseases; Child; Dextrans; Hematoma; Hematoma, Subdural; Humans; Isoniazid; Leukemia; Leukemia, Lymphoid; Mercaptopurine; Norepinephrine; Oleandomycin; Paraplegia; Prednisone; Streptomycin; Tetracycline

Topics: Aldehydes; Anilides; Animals; Antineoplastic Agents; Cyclophosphamide; Humans; Leukemia; Leukemia L1210; Leukemia, Experimental; Leukemia, Lymphoid; Mercaptopurine; Methotrexate; Mice; Neoplasms; Neoplasms, Experimental; Pharmacology; Research; Vincristine

Topics: Busulfan; Drug Therapy; Helminthiasis; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Mercaptopurine

Topics: Carbon Isotopes; Chromatography; Glucosyltransferases; Humans; Leukemia; Leukemia, Lymphoid; Liver; Mercaptopurine; Metabolism; Nucleosides; Oxidoreductases; Rats; Research; Spectrophotometry; Xanthines

Topics: Antineoplastic Agents; Busulfan; Child; Cyclophosphamide; Dactinomycin; Humans; Hydroxyurea; Leukemia; Leukemia, Lymphoid; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Mercaptopurine; Neoplasms; Neuroblastoma; Sarcoma; Urea

Topics: Adrenal Cortex Hormones; Adrenocorticotropic Hormone; Alkylating Agents; Anemia; Anemia, Hemolytic, Autoimmune; Busulfan; Chlorambucil; Cyclophosphamide; Folic Acid Antagonists; Hemorrhage; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Mercaptopurine; Neoplasms; Nitrogen Mustard Compounds; Phosphorus Isotopes; Splenectomy; Thioguanine; Triethylenemelamine

Topics: Adrenal Cortex Hormones; Antineoplastic Agents; Asian People; Busulfan; DNA; DNA, Neoplasm; Epidemiology; Formates; Geriatrics; Humans; Infant; Japan; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Mercaptopurine; Mitomycin; Neoplasms; Prednisolone; RNA; RNA, Neoplasm

Topics: Adolescent; Child; Humans; Infant; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Mercaptopurine; Methotrexate; Neoplasms; Prednisone; Prognosis

Topics: Busulfan; Chlorambucil; Cyclophosphamide; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Mercaptopurine; Methotrexate; Mustard Plant; Neoplasms; Splenomegaly; Steroids; Uracil

Topics: Adolescent; Blood Cell Count; Blood Platelets; Bone Marrow; Bone Marrow Transplantation; Erythrocytes; Erythrocytes, Abnormal; Erythropoiesis; Hemoglobins; Humans; Leukemia; Leukemia, Lymphoid; Leukocyte Count; Mercaptopurine; Prednisolone; Reticulocytes; Tissue Banks; Transplantation, Autologous

Topics: Adolescent; Child; Hematoma; Hematoma, Epidural, Cranial; Hematoma, Subdural; Humans; Hydrocephalus; Leucovorin; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Meninges; Mercaptopurine; Methotrexate; Pathology; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prednisone; Radiography; Subarachnoid Hemorrhage; Vinblastine

Topics: Adolescent; Aneuploidy; Antineoplastic Agents; Bone Marrow Cells; Child; Chromosome Aberrations; Chromosome Disorders; Cyclophosphamide; Genetics, Medical; Humans; Leukemia; Leukemia, Lymphoid; Mercaptopurine; Methotrexate; Prednisone; Research; Vincristine

Topics: Adolescent; Adrenal Cortex Hormones; Child; Drug Therapy; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Mercaptopurine; Methotrexate; Neoplasms; Prednisone

Topics: Child; Drug Therapy; Humans; Hydrocortisone; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Mercaptopurine; Methotrexate; Periodicity; Prednisone; Prognosis; Statistics as Topic; Stem Cells

Topics: Child; Drug Therapy; Encephalitis; Humans; Leukemia; Leukemia, Lymphoid; Lymphocytes; Mercaptopurine; Prednisone

Topics: Dexamethasone; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Lymphocytes; Mercaptopurine; Methylprednisolone; Prednisolone; Prednisone

Topics: Busulfan; Chlorambucil; Cyclophosphamide; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Mercaptopurine; Methotrexate; Prednisone; Triamcinolone

Topics: Cause of Death; Child; Death, Sudden; Folic Acid; Humans; Intussusception; Leukemia; Leukemia, Lymphoid; Lymphocytes; Lymphoma, Non-Hodgkin; Mercaptopurine; Steroids

Topics: Busulfan; Hodgkin Disease; Inflammation; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Leukocyte Count; Lymphoma; Lymphoma, Non-Hodgkin; Mercaptopurine; Nitrogen Mustard Compounds; Skin Tests; Skin Window Technique

Topics: Adolescent; Black People; Colchicine; Gout; Humans; Leukemia; Leukemia, Lymphoid; Lymphocytes; Mercaptopurine; Prednisone; Toxicology

Topics: Animals; Antineoplastic Agents; Antiviral Agents; Cyclophosphamide; Fluorouracil; Leukemia; Leukemia, Experimental; Leukemia, Lymphoid; Melphalan; Mercaptopurine; Mice; Oncogenic Viruses; Pathology; Pharmacology; Rauscher Virus; Research; Splenomegaly; Thiosemicarbazones; Vincristine

Topics: Adrenal Cortex Hormones; Antineoplastic Agents; Busulfan; Folic Acid Antagonists; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Mercaptopurine; Neoplasms; Nitrogen Mustard Compounds

Topics: Busulfan; Child; Chlorambucil; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Mercaptopurine; Neoplasms; Phosphorus Isotopes; Prednisolone; Prednisone; Urethane

Topics: Adrenal Cortex Hormones; Aminopterin; Child; Humans; Infant; Leukemia; Leukemia, Lymphoid; Mercaptopurine

Topics: Child; Humans; Infant; Leukemia; Leukemia, Lymphoid; Lymphatic Vessels; Mercaptopurine

Topics: Humans; Leukemia; Leukemia, Lymphoid; Mercaptopurine; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Purines

Topics: Acute Disease; Humans; Leukemia; Leukemia, Lymphoid; Mercaptopurine; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Purines