mercaptopurine and Leukemia--Myeloid--Acute

Topics: Antineoplastic Combined Chemotherapy Protocols; Clinical Trials as Topic; Consolidation Chemotherapy; Cytarabine; Daunorubicin; Drug Discovery; Etoposide; Hematopoietic Stem Cell Transplantation; Humans; Idarubicin; Induction Chemotherapy; Leukemia, Myeloid, Acute; Leukemia, Promyelocytic, Acute; Maintenance Chemotherapy; Mercaptopurine; Methotrexate; Molecular Targeted Therapy; Mutation; Recurrence; Tretinoin; Vincristine

Therapy-related myelodysplastic syndrome (t-MDS) and therapy-related acute myelogenous leukemia (t-AML) in patients with acute promyelocytic leukemia (APL) are rare events. The cumulative exposure to chemotherapy with alkylating agents and topoisomerase II inhibitors is associated with t-AML that may develop any time after the completion of the treatment. We report the case of an acquired AML who previously received therapy for APL, after two years of being diagnosed. The diagnosis was established by morphologic findings, membrane markers, cytogenetic studies, and fluorescence in situ hybridization (FISH). To our knowledge this is the first documented case in Puerto Rico of a patient with APL that developed a t-AML without the characteristic chromosomal and morphologic findings of APL.

Topics: Adult; Antineoplastic Agents, Alkylating; Antineoplastic Combined Chemotherapy Protocols; Chromosomes, Human, Pair 15; Chromosomes, Human, Pair 17; Chromosomes, Human, Pair 21; Chromosomes, Human, Pair 3; Chromosomes, Human, Pair 7; Cytarabine; Daunorubicin; Drug Synergism; Fatal Outcome; Humans; Leukemia, Myeloid, Acute; Leukemia, Promyelocytic, Acute; Male; Mercaptopurine; Methotrexate; Mitoxantrone; Monosomy; Neoplasms, Second Primary; Translocation, Genetic; Tretinoin

Since 1981, the Children's Cancer and Leukemia Study Group (CCLSG) has developed a series of protocols for treatment of acute childhood leukemia in children. Life-table analysis of serial CCLSG protocols for acute lymphoblastic leukemia (ALL) revealed that the outcome of overall All has gradually improved with a increase of the event free survival (EFS) rates; 41.4 +/- 3.6% at 14 years for the 811 protocol, 51.3 +/- 3.5% at 11 years for the 841 protocol, 56.7 +/- 3.1% at 8 year for the 874 protocol, and 78.2 +/- 3.1% at 5 year for the 911 protocol. Treatment outcome and prognostic factors were evaluated in 152 children with acute myeloblastic leukemia (AML) treated on three consecutive protocols (ANLL-861, 8912 and 9205) of CCLSG. Forty-two of these 46 patients (91.3%) in the ANLL-9205 protocol achieved complete remission and 58.8% of these patients projected a 3-year disease free survival. These results were apparently superior to those obtained with the ANLL-861 and 8912 protocols, which used conventional doses of multiple drugs followed by a moderate post remission chemotherapy of long duration. This favorable response with the ANLL-9205 protocol was mainly to high induction rate of patients with the M4 and M5 subtypes, as compared to those in the previous two protocols. An older age (> or = 8 years) and high WBC count (> or = 10 x 10(9)/l) predicted an increased risk of relapse in multivariate analyses; patients with an age > 8 years and WBC counts > or = 10 x 10(9)/l had a 4.5 times higher risk of relapse than patients without these adverse features.

Topics: Antineoplastic Combined Chemotherapy Protocols; Child; Cytarabine; Daunorubicin; Disease-Free Survival; Doxorubicin; Humans; Leukemia, Myeloid, Acute; Mercaptopurine; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prednisolone; Prognosis; Remission Induction; Survival Rate; Treatment Outcome; Vincristine

Due to advances in chemotherapy, differentiation therapy and bone marrow transplantation (BMT), adult acute myeloid leukemia (AML) has become a curable disease, and we are making further efforts to heighten the cure rate. The JALSG AML 89 study resulted in a 77% complete remission (CR) rate in 326 adults with AML, and a 38% 4.5-year disease-free survival (DFS) in CR cases. The JALSG AML92 study for APL with all-trans retinoic acid resulted in a 89% CR rate in 196 and 64% 4-year DFS in CR cases.

Topics: Adolescent; Adult; Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Clinical Trials as Topic; Cytarabine; Daunorubicin; Drug Resistance, Neoplasm; Humans; Infusions, Intravenous; Leukemia, Myeloid, Acute; Mercaptopurine; Middle Aged; Prednisolone; Tretinoin

Due to the advance of chemotherapy and bone marrow transplantation (BMT), adult acute leukemia has become a curable disease. Since in BMT a good prognosis is obtained in chemotherapy-induced remission cases, chemotherapy plays a major role for the cure of this disease. In acute myeloid leukemia, the JALSG AML 89 study resulted in a 77% complete remission (CR) rate in 326 adults, 38% of whom had a 4.5-year diseases-free survival (DFS) rate in CR cases. However, the results of acute lymphoblastic leukemia in the JALSG ALL 87 study were not satisfactory; 84% CR in 116 adults and only 24% 6-year DFS.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Cytarabine; Daunorubicin; Disease-Free Survival; Humans; Leukemia, Myeloid, Acute; Mercaptopurine; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prednisolone; Prognosis; Remission Induction; Survival Rate

A 65-year old female was diagnosed to have acute nonlymphocytic leukemia (M2) in July, 1990. Complete remission was achieved by BHAC-DMP (enocitabine, daunorubicin, 6-mercaptopurine, prednisolone) therapy. Complete remission had continued without symptoms for about two years. Uterial infiltration of leukemic cells occurred in May, 1992, followed by bone marrow relapse after two months. The second hematological complete remission was obtained after one course of the chemotherapy, but uterial infiltration of leukemic cells had still remained.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Cytarabine; Daunorubicin; Female; Humans; Leukemia, Myeloid, Acute; Leukemic Infiltration; Mercaptopurine; Prednisolone; Recurrence; Remission Induction; Uterus; Vincristine

The articles selected in this review highlight some advances in the use of the "old standards" methotrexate and 6-mercaptopurine for the treatment of children with acute lymphoblastic leukemia, especially the laboratory studies, which may allow a "pharmacologic phenotyping" to identify children most likely to relapse. In addition, we review the use of "newer" drugs (epipodophyllotoxins), which may be effective but are also associated with high morbidity (ie, secondary acute myeloid leukemia). As a second issue, "dose intensity" and the use of high-dose chemotherapy followed by bone marrow transplantation will be challenged, especially in light of peripheral stem cell harvest and the use of growth factors.

Topics: Bone Marrow Transplantation; Child; Combined Modality Therapy; Growth Substances; Humans; Leukemia, Myeloid, Acute; Medical Oncology; Mercaptopurine; Methotrexate; Pediatrics; Phenotype; Podophyllotoxin; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Quality of Life; Recurrence; Survival Rate

We describe a 45-year-old female who developed acute myelogenous leukemia (AML) associated with a mediastinal mass. The patient achieved a complete remission accompanied by resolution of the mediastinal mass following intensive chemotherapy alone. A review of the literature disclosed ten AML patients with a mediastinal tumor; all five patients who had mediastinal granulocytic sarcoma treated by local irradiation prior to developing AML, eventually relapsed as frank leukemia and died soon afterwards. On the other hand, three of the other five patients who simultaneously developed both a mediastinal tumor and overt AML achieved complete remission with combination chemotherapy. In conclusion, intensive chemotherapy should be considered for a patient with granulocytic sarcoma of the mediastinum, irrespective of the concomitant leukemia.

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Daunorubicin; Female; Follow-Up Studies; Humans; Leukapheresis; Leukemia, Myeloid, Acute; Mediastinal Neoplasms; Mercaptopurine; Middle Aged; Prednisolone; Radiography, Thoracic; Remission Induction; Time Factors; Tomography, X-Ray Computed

We report two additional patients with acute myeloid leukemia (AML) and a translocation between chromosomes 7 and 11: t(7;11)(p15;p15). One patient was diagnosed as having AML-M2 and the other as AML with myelofibrosis. Both patients had low-level neutrophil alkaline phosphatase (NAP) scores. In the literature, only 15 AML patients with t(7;11)(p15;p15) have been reported; nine of them had an AML-M2 morphology, and all had a decreased NAP score. Moreover, mean survival of the reported AML patients with t(7;11)(p15;p15) was 15 months, although 85% of them obtained complete remission, indicating that this type of leukemia frequently tends to relapse. These findings indicate a strong association between the chromosome abnormality and hematologic manifestations of this disease.

Topics: Acute Disease; Adult; Alkaline Phosphatase; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Chromosomes, Human, Pair 11; Chromosomes, Human, Pair 7; Cytarabine; Daunorubicin; Female; Humans; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Middle Aged; Neutrophils; Prednisolone; Primary Myelofibrosis; Remission Induction; Translocation, Genetic

With the objective of establishing the optimal therapy for minimally differentiated acute myeloid leukemia (AML-M0), we examined the therapeutic results of five AML-M0 cases and reviewed the literature. In a series of 63 patients with newly diagnosed acute leukemia who were admitted to the Main Hospital of Nippon Medical School, five patients fit the criteria for AML-M0: negative myeloperoxidase (MPO) and Sudan black B reaction by light microscopy, negative for B- and T-lineage markers, and positive for myeloid markers. They were treated by means of AdVP [adriamycin, vincristine, and prednisolone (PSL)] therapy and/or BHAC-DMP [behenoylcytosine arabinoside (BHAC), daunorubicin (DNR), 6-mercaptopurine (6-MP), and PSL] therapy. The AdVP therapy was unsuccessful in the two patients who received it, while a complete remission (CR) was achieved with the BHAC-DMP therapy in three of four patients. Although one patient treated with BHAC-DMP did not achieve CR, his blasts were apparently sensitive to the therapy. In assessable cases in the literature where leukemic blasts were MPO-negative, myeloid marker-positive and B- and T-lineage marker-negative, CR was achieved in 54.5% and 44.4% with anti-acute myeloid leukemia therapy and anti-acute lymphocytic leukemia therapy, respectively. Five cases in the literature were treated with a chemotherapeutic regimen containing BHAC [or cytosine arabinoside (Ara-C)], DNR, and 6-MP, and all achieved CR. The regimen containing BHAC (or Ara-C), DNR, and 6-MP may be useful as induction chemotherapy for AML-M0.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Azo Compounds; Cytarabine; Daunorubicin; Humans; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Middle Aged; Naphthalenes; Peroxidase; Prednisolone; Remission Induction

Results of treatment of AML have substantially progressed within the last decade. In almost all cases, the AML 3-year-survival rate did not exceed 1% in the 1960s. The 5-year disease-free survival rate now is ranges from 10% to 25% in adults and up to 45% in children. The 3-year survival at our hospital is 50%. Recent chemotherapy for acute leukemia is aimed at not only remission induction but also cure of the disease. Although some hematologists claim to stop chemotherapy as early as possible, there is considerable controversy regarding the total length of postremission treatment. Bone marrow transplantation is increasingly used to treat patients with acute leukemia in many facilities. Bone marrow transplantation assures a lower relapse rate than with chemotherapy alone. The limitations are the risk of transplant-related mortality, lack of a histo-compatible donor and advanced age. To achieve substantial improvement in results of AML treatment requires the development of new drugs, and the reduction of transplant-related death. An attempt to establish registries of HLA type for the transplantation from unrelated, HLA-identical donors is now under way.

Topics: Adult; Age Factors; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Child; Cytarabine; Daunorubicin; Heart; Humans; Leukemia, Myeloid, Acute; Mercaptopurine; Middle Aged; Prednisolone; Prognosis; Remission Induction; Vincristine

Topics: Acute Disease; Adult; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Daunorubicin; Humans; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Pericarditis

Although cytotoxic immunosuppressive agents play an unquestionably useful role in treating many neoplastic and non-neoplastic disorders, there is accumulating evidence that the toxicity associated with their use is considerable. The therapeutic successes obtained with antitumor agents have led to increases in the life span of cancer patients, but have also provided the opportunity for this toxicity to become manifest. A search of the available literature was carried out, with emphasis on cases in which a malignancy developed in patients following chemotherapy for either neoplastic or non-neoplastic (e.g., renal transplantation, psoriasis) conditions; particular focus was given to the incidence of acute myelogenous leukemia in various groups of Hodgkin's disease and multiple myeloma patients. That patients with nonmalignant conditions treated with cytotoxic immunosuppressive agents are also at increased risk of developing a malignancy raises the possibility that these agents may have oncogenic potential. Therefore, one may be faced with the paradox that the patients benefiting most from chemotherapy may be at highest risk of suffering its consequences.

Topics: Alkylating Agents; Animals; Antineoplastic Agents; Azathioprine; Burkitt Lymphoma; Choriocarcinoma; Cyclophosphamide; Dactinomycin; Female; Hodgkin Disease; Humans; Immunosuppressive Agents; Kidney Neoplasms; Leukemia, Myeloid, Acute; Lymphoma; Mechlorethamine; Melphalan; Mercaptopurine; Methotrexate; Mice; Multiple Myeloma; Neoplasms; Prednisone; Pregnancy; Procarbazine; Time Factors; Vincristine

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: Antineoplastic Agents; Blood Platelet Disorders; Bromine; Busulfan; Dose-Response Relationship, Drug; Galactitol; Humans; Hydroxyurea; Immunotherapy; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Mannitol; Mercaptopurine; Splenectomy; Uracil Mustard

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

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: 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: 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: 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: Adrenal Cortex Hormones; Anti-Bacterial Agents; Antineoplastic Agents; Busulfan; Cyclophosphamide; Folic Acid Antagonists; Humans; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Mercaptopurine

Topics: Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Apoptosis; CASP8 and FADD-Like Apoptosis Regulating Protein; Cyclophosphamide; Cytarabine; Daunorubicin; Down-Regulation; Drug Eruptions; Hidradenitis; Homoharringtonine; Humans; Incidence; Leukemia, Myeloid, Acute; Mercaptopurine; Myeloid Cell Leukemia Sequence 1 Protein; Neoplasm Proteins; Neutrophils; Protein Kinase Inhibitors; Sweat Glands

Management of unfit AML patients is a therapeutic challenge. Most hematologists tend to avoid aggressive treatment leaving patients with a choice of best supportive care. We hypothesized that metronomic chemotherapy could be an alternative treatment for unfit AML patients.. A multi-center randomized controlled trial was conducted in seven university-affiliated hospitals in Thailand. Unfit AML patients were recruited and followed up from December 2014 to December 2017. Patients were randomly assigned to receive either metronomic chemotherapy or palliative hydroxyurea. Overall survival rates were compared using Cox's proportional hazard survival analysis.. A total of 81 eligible patients were randomly allocated and included for ITT analysis. The OS rate was higher in group receiving metronomic chemotherapy than in group receiving palliative treatment at 6 and 12 months with borderline significance (6 months HR 0.60; 95%CI 0.36, 1.02; p-value 0.060; 12 months: HR 0.66; 95%CI 0.41, 1.08; p-value 0.097).. Metronomic chemotherapy could prolong survival time of unfit AML patients, especially in the first 12 months after diagnosis without increasing treatment-associated adverse events.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Etoposide; Female; Follow-Up Studies; Humans; Hydroxyurea; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Middle Aged; Prednisolone; Prognosis; Survival Rate

We conducted a prospective, multicenter cooperative study to compare two courses of modified intermediate-dose cytarabine (Ara-C) (mIDAC; Ara-C at a dose of 1.0 g/m(2) every 12 hours for 5 days) versus high-dose Ara-C (HDAC; Ara-C at a dose of 2.0 g/m(2) every 12 hours for 5 days) in post-remission therapy for acute myeloid leukemia (AML) to confirm the post-remission antileukemic efficacy and safety of mIDAC.. Twenty-six newly diagnosed patients with AML underwent remission induction therapy consisted of behenoyl Ara-C, mitoxantrone, etoposide, and 6-mercaptopurine. Post-remission therapy included four courses of consolidation and four courses of intensification. Patients who achieved complete remission (CR) were randomly assigned to mIDAC or HDAC for the second course of consolidation. The third course of intensification was the same as the second course of consolidation. Other post-remission therapies were the same in each group.. Twenty-two patients (84.6%) achieved CR and 21 patients were randomly assigned to receive either mIDAC (n=11) or HDAC (n=10). The predicted 4-year relapse-free survival for the mIDAC group and for the HDAC group were 49% and 56%, respectively (p=0.86). Although HDAC developed severe leukocytopenia compared to mIDAC, there were no significant differences between HDAC and mIDAC in the incidence of ≥grade 3 and ≥grade 4 documented infections. The mean lowest white blood cell count (WBC) after HDAC was significantly lower than that after mIDAC (0.208±0.120×10(3)/mm(3) and 0.459±0.333×10(3)/mm(3), respectively, p<0.05). The time to WBC recovery to 2.0×10(3)/mm(3) after HDAC was significantly longer than that after mIDAC (34.3±12.1 days and 27.1±9.5 days, respectively, p<0.05).. This study suggests that mIDAC may have an equivalent post-remission antileukemic efficacy to HDAC with less myelosuppression for AML patients.

Topics: Adult; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Consolidation Chemotherapy; Cytarabine; Disease-Free Survival; Dose-Response Relationship, Drug; Drug Administration Schedule; Etoposide; Female; Humans; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Middle Aged; Mitoxantrone; Prospective Studies; Remission Induction; Vinblastine; Vincristine; Young Adult

A major concern in the treatment of patients with acute myeloid leukemia (AML) is how to prevent disease recurrences. Although intensive consolidation therapy has proven useful, the effectiveness of maintenance therapy remains controversial.. Seven hundred eighty-nine patients ages 15-64 (median: 45 yrs) with de novo AML received induction therapy, which consisted of cytosine arabinoside (at a dose of 100 mg/m(2) on Days 1-7) and idarubicin (at a dose of 12 mg/m(2) on Days 1-3). The patients who achieved complete remission (CR) were then randomized into groups that received either four courses of standard-dose consolidation therapy without maintenance (Arm A) or three courses of standard-dose consolidation and six courses of maintenance therapy (Arm B).. In total, 78.7% of patients achieved CR. The 5-year overall survival (OS) rate for the 789 eligible patients was 46.9%, and the disease-free survival (DFS) rate for the 621 patients who achieved CR was 32.9%. The 5-year OS rate for Arm A was 52.4%, and 58.4% for Arm B (P = 0.599). The 5-year DFS rate for the patients who achieved CR was 35.8% in Arm A and 30.4% in Arm B (P = 0.543). In analyzing the data according to the risk groups, no statistical difference was observed either in the 5-year OS rate or in the 5-year DFS rate between the 2 arms.. In the current study, the Japan Adult Leukemia Study Group's conventional postremission therapy (three courses of standard-dose consolidation and six courses of maintenance therapy) was replaced successfully by a shorter duration of four courses of standard-dose consolidation therapy without the need for additional maintenance therapy.

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Daunorubicin; Disease-Free Survival; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Idarubicin; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Middle Aged; Mitoxantrone; Probability; Remission Induction; Risk Assessment; Treatment Outcome; Vincristine; Vindesine

To determine whether the use of maintenance therapy (MT) delivered after intensive induction and consolidation therapy confers any advantage in childhood acute myeloid leukemia (AML).. A total of 268 children with AML were registered in the Leucámie Aiquë Myéloïde Enfant (LAME) 89/91 protocol. This regimen included an intensive induction phase (mitoxantrone plus cytarabine) and, for patients without allograft, two consolidation courses, one containing timed-sequential high-dose cytarabine, asparaginase, and amsacrine. In the LAME 89 pilot study, patients were given an additional MT consisting of mercaptopurine and cytarabine for 18 months. In the LAME 91 trial, patients were randomized to receive or not receive MT.. A total of 241 (90%) of 268 patients achieved a complete remission. The overall survival and event-free survival at 6 years were 60% +/- 6% and 48% +/- 6%, respectively. For the complete responders after consolidation therapy, the 5-year disease-free survival was not significantly different in MT-negative and in MT-positive randomized patients (respectively, 60% +/- 19% v 50% +/- 15%; P =.25), whereas the 5-year overall survival was significantly better in MT-negative randomized patients (81% +/- 13% v 58% +/- 15%; P =.04) due to a higher salvage rate after relapse.. More than 50% of patients can be cured of AML in childhood. Either drug intensity or each of the induction and postremission phases may have contributed to the outstanding improvement in outcome. Low-dose MT is not recommended. Exposure to this low-dose MT may contribute to clinical drug resistance and treatment failure in patients who experience relapse.

Topics: Amsacrine; Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Bone Marrow Transplantation; Child; Child, Preschool; Cytarabine; Disease-Free Survival; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Infusions, Intravenous; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Mitoxantrone; Prospective Studies; Recurrence; Treatment Outcome

Twenty-nine patients aged 60-75 years with newly diagnosed acute myelogenous leukemia (AML) were randomized to receive BHAC-DM either at a reduced dose (S-1 group, n = 13; BHAC 150 mg/m2 1-7 day, DNR 30 mg/m2 1-3 day, 6MP 70 mg/m2 1-7 day) or the conventional dose (S-2 group, n = 16; BHAC 200 mg/m2 1-7 day, DNR 40 mg/m2 1-3 day, 6MP 70 mg/m2 1-7 day). On day 7, patients were given therapy for 2 more days if the ratio of blasts in their bone marrow was more than 15%. Granulocyte-colony stimulating factor was injected when the leukocyte count decreased below 1,000/microliter. The rates of complete remission were 46.2% in the S-1 group and 43.8% in the S-2 group. No significant differences in response distinguished the 2 groups. The mortality rate during myelosuppression was 1/13 in the S-1 group and 1/16 in the S-2 group. The rate of treatment-related death was 10.1% for all patients. Grade-4 adverse effects were not seen in any of the patients. We concluded that the conventional dose of BHAC-DM was as acceptable as the reduced dose in elderly patients with AML.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Daunorubicin; Drug Administration Schedule; Female; Humans; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Prednisolone; Prognosis; Prospective Studies; Remission Induction; Vincristine

A multicenter prospective randomized study was undertaken to assess the efficacy of etoposide added to the standard remission induction therapy for acute myeloid leukemia (AML). Consecutively registered newly diagnosed adult AML patients were randomized to receive either daunorubicin (40 mg/m2/day x 4 or more), behenoyl cytarabine (200 mg/m2/day x 10 or more) and 6-mercaptopurine (70 mg/m2/day x 10 or more) (BH-AC-DM), or the same three drugs plus etoposide (100 mg/m2/day x 5) (BH-AC-EDM) for response-oriented individualized induction therapy. The patients achieving complete remission (CR) received the same 3 courses of consolidation therapy followed by 6 courses of maintenance/intensification therapy. M3 was excluded and M0 was included. Of 667 patients registered, 655 were evaluable. The median age was 49 years (range, 15 to 85). CR rates were 77% in the BH-AC-DM group and 75% in the BH-AC-EDM group. In M4 patients, CR rates were 86% and 69% (p = 0.009), and, in M5, 80% and 77% (p = 0.810) in the BH-AC-DM and BH-AC-EDM groups, respectively. The predicted 6-year overall survival rates were 30% and 38% for BH-AC-DM and BH-AC-EDM groups, and the disease-free survival (DFS) rates of CR patients were 25% and 35% (p = 0.925), respectively. In conclusion, the present study failed to show any advantage of the addition of etoposide to the standard individualized induction therapy in adult AML, even among M4 and M5. These above data have already been published in the Int J Hematol (70: 87-104, 1999).

Topics: Adolescent; Aged; Aged, 80 and over; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Daunorubicin; Disease-Free Survival; Drug Administration Schedule; Etoposide; Humans; Leukemia, Myeloid, Acute; Mercaptopurine; Middle Aged; Prospective Studies

We report here on treatment results of consecutive CCLSG NHL studies (NHL855, 1985-1989; NHL890, 1989-1996). The NHL855 protocol consisted of an induction phase of five drugs (VCR, PRD, CPM, DXR, and high-dose MTX) and a maintenance phase of 7 drugs. The probabilities of EFS at 7 years were 78% (SE, 10%) for the patients with localized disease, and 38% (SE, 7%) for those with advanced disease. In the NHL 890 protocol, the patients were assigned to two different treatment groups according to their histology and received different consolidation therapy; non-lymphoblastic subtype was treated almost identically to NHL855 while LASP and VP-16 were newly added for the lymphoblastic subtype. The 7-year EFS improved to 91% (SE, 6%) for localized disease, and 61% (SE, 6%) for advanced disease. A remarkable improvement was particularly evident for lymphoblastic type with mediastinal mass. Optional trial of high-dose sequential chemotherapy and peripheral blood progenitor cell auto grafting resulted in an unfavorable outcome. The 7-year EFS according to main histological subgroups were as follows: 84% (10%) for large cell type, 67% (11%) for Burkitt's-type, 58% (10%) for lymphoblastic type. Secondary cancer occurred in two of the 163 patients studied. Both patients were AML (M0/M4) and MLL rearrangement was detected in the M4 case.

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Child; Child, Preschool; Cyclophosphamide; Cytarabine; Doxorubicin; Etoposide; Female; Follow-Up Studies; Humans; Hydrocortisone; Infant; Leukemia, Myeloid, Acute; Lymphoma, Non-Hodgkin; Male; Mercaptopurine; Methotrexate; Neoplasms, Second Primary; Prednisolone; Remission Induction; Treatment Outcome; Vincristine

Thirty-two adults (median age 48 years) with acute myelogenous leukemia (excluding M3) have been treated with short-term intensive therapy (M90 therapy). After induction therapy with daunorubicin, cytosine arabinoside (araC), 6-mercaptopurine, prednisolone, mitoxantrone (MIT) and etoposide (VP16), three regimens of post-induction chemotherapy were conducted as short an intercycle time as possible. The first regimen was with MIT and VP16, the second with behenoyl-araC and aclarubicin and the third with VP16, araC, vincristine and vinblastine. No further therapy was given. Complete remission was achieved in 24 (75%) of 32 patients and 24% of all patients were projected to remain free of disease at 5 years. The median duration of the entire therapy was 120 days with a range of 95 to 157 days. Post-induction regimens resulted in severe myelosuppression and their toxicity included treatment-related death in one patient. The treatment results of this short-term therapy were comparable to a former treatment protocol, M84 therapy with a median duration of the entire treatment therapy of 515 days. To confirm the advantages of such short-term therapy, prospective randomized comparisons with conventional post-induction therapy may be required.

Topics: Aclarubicin; Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Daunorubicin; Etoposide; Humans; Leukemia, Myeloid, Acute; Mercaptopurine; Middle Aged; Mitoxantrone; Time Factors; Vinblastine; Vincristine

In order to analyse the clinical characteristics and outcome in acute myelogenous leukemia, 129 consecutive adult patients admitted to our hospital over a 10-year period, from August 1984 to July 1994, were studied. Their median age was 51 years, 17 (13.2%) of them had antecedent myelodysplastic syndrome (MDS) and 9 (7.0%) had secondary leukemia. Seventy-eight patients (60.5%) were considered eligible for cure-oriented intensive chemotherapy. Forty-four patients were ineligible of one or more of the following; age over 70, antecedent MDS or secondary leukemia. Additional 7 patients were excluded due to concurrent severe diseases. The median survival of the 129 patients was 441 days with an actuarial 5-year survival of 28.6 +/- 4.4%, and the disease-free survival (DFS) decreased with the increasing age of the patient. In 78 patients who were eligible for intensive chemotherapy, complete remission was achieved in 84.6% and overall DFS was 41.1 +/- 5.9% at 5 years, and their survival was longer than that of ineligible patients. It was suggested that considerable selection of patients, for example, due to old age, already existed before visiting our hospital. Analysis of clinical data of unselected patients might enable the development of a rational approach to the management of elderly patients.

Topics: Adolescent; Adult; Age Factors; Aged; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Daunorubicin; Disease-Free Survival; Etoposide; Female; Humans; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Middle Aged; Mitoxantrone; Patient Selection; Prednisolone; Remission Induction; Retrospective Studies; Treatment Outcome

Seventy-three children with acute nonlymphocytic leukemia (ANLL) have been treated with ANLL-85 and ANLL-88 protocol at Kyushu-Yamaguchi Children's Cancer Study Group between June, 1985 and February, 1993. Ten boys and 10 girls (0y4m-16ylm) were treated with the ANLL-85 protocol. The complete remission (CR) rate was 75% and the 5-year event free survival (EFS) was 20 +/- 9%. It was terminated because of frequent early relapse (within 6 months after CR). Thirty-four boys and 19 girls (0y3m-17ylm) were treated with the ANLL-88 protocol. The CR rate was 85% and the 5-year EFS was 32 +/- 7%. Early relapse rate with ANLL-88 was lower than that of ANLL-85, however 9 cases relapsed after terminating therapy. Although bone marrow transplantation (BMT) from related donors during the first CR was effective in ANLL-88, EFS was not improved. Recognition of risk factors and appropriate chemotherapy regimens with or without the support of stem cell transplantation may be necessary to cure children with ANLL.

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Child; Child, Preschool; Cyclophosphamide; Cytarabine; Daunorubicin; Drug Administration Schedule; Etoposide; Female; Humans; Infant; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Prednisolone; Recurrence; Remission Induction; Survival Rate; Vincristine

Topics: Adolescent; Adult; Amsacrine; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Daunorubicin; DNA; DNA Adducts; Doxorubicin; Drug Administration Schedule; Humans; Leukemia, Myeloid, Acute; Mercaptopurine; Methotrexate; Middle Aged; Prednisolone; Prednisone; Survival Analysis; Thioguanine; Vincristine

A phase II pediatric trial of a continuous intravenous infusion of 6-mercaptopurine (6MP) in patients with refractory leukemia was performed. The dosing schedule, 50 mg m-2 h-1 for 48 h, was based on the results of a previous phase I trial of this approach. Among the 40 children treated for acute lymphoblastic leukemia (ALL), all of whom had received prior therapy with oral 6MP, 1 complete and 1 partial response were achieved. No response was observed in 17 patients with refractory acute nonlymphocytic leukemia (ANLL). Reversible hepatotoxicity, the primary dose-limiting toxicity, was observed in approximately 50% of cases. Mucositis was encountered infrequently and was usually not severe. 6MP given on the present continuous intravenous infusion schedule overcomes the limited and variable bioavailability of oral 6MP but shows limited activity as induction agent in children with recurrent ALL.

Topics: Adolescent; Adult; Child; Child, Preschool; Drug Administration Schedule; Drug Evaluation; Humans; Infant; Infusions, Intravenous; Leukemia, Myeloid, Acute; Mercaptopurine; Precursor Cell Lymphoblastic Leukemia-Lymphoma

Between August 1978 and September 1982, 642 patients with newly diagnosed acute myelogenous leukemia (AML) were entered onto a Southwest Oncology Group Study which addressed four questions. (i) What is the comparative utility of rubidazone versus adriamycin in remission induction? (ii) What is the role of prophylactic intrathecal therapy in AML? (iii) Does late intensification affect treatment outcome? (iv) Does maintenance with levamisole affect disease-free survival or overall survival? Among 611 evaluable patients, 329 (54%) achieved complete remission. There was no difference in the remission rate between those patients receiving rubidazone (54%) and those receiving adriamycin (54%) as part of the induction regimen. Prophylactic intrathecal therapy with cytosine arabinoside had no effect on the incidence of central nervous system disease or survival. After nine months of complete remission, patients were randomized between late intensification with POMP (mercaptopurine + vincristine + methotrexate + prednisone) or continued maintenance with OAP (vincristine + cytosine arabinoside + prednisone). T patients randomized to late intensification had better survival and disease-free survival, compared to those randomized to receive no late intensification (p = 0.027 and 0.030, respectively). At twelve months of remission, surviving patients were randomized to receive levamisole or no further treatment. There was no evidence that levamisole affected survival or disease-free survival.

Topics: Antineoplastic Combined Chemotherapy Protocols; Brachytherapy; Combined Modality Therapy; Daunorubicin; Doxorubicin; Humans; Immunotherapy; Leukemia, Myeloid, Acute; Levamisole; Mercaptopurine; Methotrexate; Nervous System Neoplasms; Prednisone; Survival Analysis; Vincristine

Thirty-one children with ANLL were treated using the 12th-ANLL Protocol of the Tokyo Children's Cancer Study Group incorporating an ACMP 2-step regimen. Induction therapy consisted of two 4-day courses of adriamycin (ADR) and cytosine arabinoside (ARA-C) given with a 7-day interval. Those patients who achieved remission were given one more course as early intensification. Late intensification consisted of a 5-day course of ARA-C and one dose of ADR which was repeated until the cumulative dosage of ADR reached 465 mg/m2. After this point, treatment was divided into 2 courses. Both courses included ARA-C and one course had achlacinomycin in addition. Twenty-seven children (87%) attained remission after one or two courses of induction therapy. Kaplan-Meyer analysis revealed that the continuous complete remission rate and event-free survival were 71% and 51%, respectively, 5 years after diagnosis. Toxicity was minimum with only one death during the remission. These results are encouraging and warrant further trials.

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Child; Child, Preschool; Cytarabine; Doxorubicin; Female; Humans; Infant; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Prednisolone; Prognosis; Survival Rate; Treatment Outcome

Twenty-three European centers participated in a randomized clinical trial (AML-5) to study the effect of androgens and immunotherapy during maintenance in adult acute myelogenous leukemia. Induction treatment consisted of Adriamycin (doxorubicin) 50 mg/m2 day 1, vincristine VCR 1 mg/m2 day 2, and cytosine arabinoside 80 mg/m2 every 12 hours by push injection days 3-9. Patients in complete remission were randomized into four groups: (1) 6-mercaptopurine 70 mg/m2 days 1-14, methotrexate 15 mg/m2 twice weekly days 15-28, and reinduction with daunorubicin 35 mg/m2 and vincristine 1 mg/m2 day 29; (2) chemotherapy as in group 1 plus stanozolol 0.15 mg/kg/day; (3) 6-thioguanine 70 mg/m2 orally on 4 consecutive days and cytosine arabinoside 80 mg/m2 subcutaneously day 5 every week; and (4) chemotherapy as in Group 3 plus irradiated blast cells treated with neuraminidase. Three hundred forty-eight patients were eligible and 295 were evaluable. The median age was 45 yrs. A complete remission was achieved in 64% of the patients, with 158 complete remissions randomized. Patients not randomized and patients receiving bone marrow transplantation (BMT) were analyzed separately. There was no difference in disease-free survival (DFS) or survival in the four maintenance arms. For patients reaching complete remission, the median DFS was 40 weeks, and median survival was 22 months with 30% surviving at 4 years. The overall survival was 18% at 4 years. There was no beneficial effect for DFS or survival by adding either immunotherapy or androgens to chemotherapy during maintenance. However, patients receiving immunotherapy seemed to have a higher rate of responses to reinduction after relapse than those in the other treatment arms.

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Child; Clinical Trials as Topic; Combined Modality Therapy; Cytarabine; Daunorubicin; Doxorubicin; Humans; Immunotherapy; Leukemia, Myeloid, Acute; Mercaptopurine; Methotrexate; Middle Aged; Prospective Studies; Random Allocation; Testosterone Congeners; Thioguanine; Time Factors; Vincristine

The Finnish Leukaemia Group has carried out a randomized, multicenter trial to study the effect of levamisole on the remission maintained with 6-mercaptopurine and methotrexate in acute myeloid leukaemia in adults. Levamisole was given on 3 consecutive days every 2 weeks. Twenty-five patients received only chemotherapy, while 26 patients received levamisole as well. The patients receiving levamisole showed significantly better remission duration than those given only chemotherapy (P = 0.033, Mantel's summary chi 2-text). There are four long term survivors in the levamisole group versus none in the chemotherapy group. The remissions have lasted 48-75 months.

Topics: Adult; Aged; Drug Administration Schedule; Follow-Up Studies; Humans; Immunotherapy; Leukemia, Myeloid, Acute; Levamisole; Mercaptopurine; Methotrexate; Middle Aged

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

Two hundred and fifty patients with acute myeloid leukaemia (AML) were randomized between 2 regimens of chemotherapy: TRAP and BARTS III. Overall, patients randomized to TRAP, which was the more intensive of the 2 regimens, fared slightly better (P = 0.06) than those on BARTS III. However, the improvement in survival associated with more intensive chemotherapy was substantial only for patients who had favourable prognostic features at presentation, such as a normal total leucocyte count, or absence of palpable liver, or, especially, age under 40. Indeed, for patients under 40, those allocated to the more intensive regimen (TRAP) lived considerably longer than those allocated to BARTS III (P less than 0.002) while for patients over 40 there was no material difference in survival between patients on the 2 protocols. It thus appears that intensive chemotherapy is likely to be more effective when favourable prognostic features are recorded.

Topics: Adolescent; Adult; Aged; Antineoplastic Agents; Child; Child, Preschool; Clinical Trials as Topic; Cyclophosphamide; Cytarabine; Daunorubicin; Drug Administration Schedule; Drug Therapy, Combination; Humans; Leukemia, Myeloid, Acute; Mercaptopurine; Methotrexate; Middle Aged; Prednisolone; Random Allocation; Thioguanine; Vincristine

In this study 523 previously untreated patients with acute myelocytic leukemia were randomly allocated to induction therapy with daunorubicin 60 mg/M2 daily X 3, cytosine arabinoside and thioguanine 100 mg/M2 each every 12 hours until marrow hypoplasia was achieved, or a 5-day course of the three drugs with daunorubicin 100 mg/M2 given on dav 1 and cytosine arabinoside plus thioguanine each given at a dose of 100 mg/M2 every 12 hours for five days. All patients received cyclophosphamide 600 mg/M2 followed in 24 hours by hydroxyurea 500 mg/M2 every six hours for four doses monthly for maintenance therapy. Patients were randomized to receive one of three antimetabolite treatments beginning 24 hours after the last dose of hydroxyurea each month for seven days. One such treatment consisted of 6-mercaptopurine 100 mg/M2 daily, another group received 6-thioguanine at the same dose daily, and the third group received 50 mg/M2 of both antimetabolites daily. There were no significant differences in complete response rate, remission duration, or survival among the various treatment groups.

Topics: Adult; Age Factors; Aged; Antineoplastic Agents; Bone Marrow; Clinical Trials as Topic; Cyclophosphamide; Cytarabine; Daunorubicin; Drug Administration Schedule; Drug Synergism; Drug Therapy, Combination; Female; Humans; Hydroxyurea; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Middle Aged; Remission, Spontaneous; Thioguanine

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

Treatment of older acute leukemia patients has been the subject of recent debate. We treated 101 acute leukemia patients in a prospective randomized trial. Fifty-seven per cent of the population was over 50. Half were treated with a mild induction program (VAMP) and half with a vigorous program (CAT). The older patients who received vigorous treatment did better than those who received mild treatment. We suggest that patients over 50 should be regarded as a separate category in design of treatment protocols in order to further maximize the benefits of therapy.

Topics: Age Factors; Aged; Antineoplastic Agents; Bone Marrow; Cytarabine; Depression, Chemical; Drug Therapy, Combination; Humans; Leukemia, Myeloid, Acute; Mercaptopurine; Methotrexate; Middle Aged; Prednisone; Prognosis; Thioguanine; Time Factors; Vincristine

Sixteen patients in an acute blast crisis of chronic myeloid leukaemia (CML) were treated with a combination of vincristine, 6-mercaptopurine, hydroxyurea and prednisone. Only two of these patients had complete remission on this treatment, while four had partial remission. This experience, comparable to that reported by others, suggests that aggressive treatment in the terminal phase of CML is justified only as part of a prospective and well-controlled study.

Topics: Adolescent; Adult; Aged; Drug Therapy, Combination; Female; Humans; Hydroxyurea; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Middle Aged; Prednisone; Prospective Studies; Remission, Spontaneous; Switzerland; Vincristine

Twenty-four children (2 to 21 years) diagnosed as having AML from 1969 to 1972 were randomized to receive either a single combination (COMP or PRAVD) or sequential combination chemotherapy (alternating POMP and PRAVD). Seventeen achieved complete remission. Patients who received POMP alone had the longest median duration of remission (1,400 days) compared to PRAVD (395 days) or POMP-PRAVD (270 days); interpretation of this difference is uncertain, since the numbers in each group are small. Fifteen patients have relapsed, four initially with CNS involvement. Successful reinduction was achieved almost exclusively for patients who had initially received POMP. Survival after first relapse was short. Patients less than 16 years had a median survival of 632 days, compared to 285 days for patiens greater than 16 (p less than 0.05). The high initial induction rate in these patients is encouraging, but the duration remission is inferior to that seen in childhood ALL. Moreover, the slope of the relapse curve is continuous over a five-year period with no definite plateau where it might appear that patients are no longer at risk of relapse. Improved methods for the treatment of childhood ALL and adult AML suggest possible new approaches to AML in children, with prophylactic treatment of central nervous system, late intensification, and immunotherapy.

Topics: Adolescent; Antineoplastic Agents; Child; Child, Preschool; Cytarabine; Daunorubicin; Drug Therapy, Combination; Female; Humans; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Methotrexate; Prednisolone; Remission, Spontaneous; Vincristine

Three hundred twenty-six patients with acute myelocytic leukemia were randomly and prospectively assigned to four therapeutic regimens: cytosine arabinoside either alone or in combination with daunorubicin, 6-mercaptopurine, or 6-thioguanine. The results in 231 qualified previously untreated patients were analyzed. The combination treatments produced a significantly greater frequency of complete or partial remission than single drug therapy. Treatment with cytosine arabinoside and thioguanine led to 48% age-adjusted complete and partial responses. The median sur survival from diagnosis of all 66 evaluable patients treated with these two drugs was 18 weeks, while the median survival for those who responded to this combination was 15 months.

Topics: Adult; Cytarabine; Daunorubicin; Drug Therapy, Combination; Female; Humans; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Middle Aged; Remission, Spontaneous; Thioguanine; Time Factors

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; Adult; Age Factors; Aged; Asparaginase; Blood Platelets; Child; Clinical Trials as Topic; Cytarabine; Daunorubicin; Drug Therapy, Combination; Female; Humans; Leukemia, Myeloid, Acute; Leukocyte Count; Lymphocytes; Male; Mercaptopurine; Middle Aged; Prednisone; Prognosis; Remission, Spontaneous; Thioguanine; Thrombocytopenia

Consecutive adult patients admitted to St. Bartholomew's Hospital with acute myelogenous leukaemia have been treated with a remission induction drug schedule consisting of daunorubicin and cytosine arabinoside. Intermittent five-day courses were used in 72 patients, and a complete remission was obtained in 39 patients (54%). An alternative drug schedule in 22 patients resulted in fewer remissions but this may have been due to age differences in the two groups. Age and initial platelet count were found to be important factors in determining the success of remission induction therapy; the older patients and those with low platelet counts responded less well.A series of 23 patients who achieved remissions was divided into two groups; one received intermittent combination chemotherapy as the only form of maintenance, and the other was given weekly immunotherapy in addition to the chemotherapy. The immunotherapy consisted of irradiated allogeneic leukaemic cells and B.C.G. Eight of the 10 patients on chemotherapy alone have already relapsed compared with five out of 13 patients in the immunotherapy group. It is hoped that these promising initial results with this form of maintenance will be confirmed as more patients enter the maintenance trials.

Topics: Acute Disease; Adolescent; Adult; Age Factors; Aged; Antineoplastic Agents; BCG Vaccine; Blood Cell Count; Blood Platelets; Child; Cytarabine; Daunorubicin; Humans; Immunotherapy; Leukemia, Myeloid, Acute; Mercaptopurine; Methotrexate; Middle Aged; Remission, Spontaneous; Thioguanine

Topics: Adolescent; Anemia, Aplastic; Bone Marrow; Bone Marrow Cells; Child; Child, Preschool; Clinical Trials as Topic; Digestive System; Drug Combinations; Female; Humans; Leukemia, Myeloid, Acute; Leukopenia; Male; Mercaptopurine; Remission, Spontaneous; Triazines; 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: 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

Topics: Adult; Antineoplastic Agents; Child; Clinical Trials as Topic; Cytarabine; Drug Synergism; Humans; Leukemia, Myeloid, Acute; Mercaptopurine; Prednisone

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

Acute myeloid leukemia (AML) is an aggressive malignancy, and many elderly/unfit patients cannot receive intensive and potentially curative therapy. These patients receive low-toxicity disease-stabilizing treatment. The combination of all-trans retinoic acid (ATRA) and the histone deacetylase inhibitor valproic acid can stabilize the disease for a subset of such patients. We performed untargeted serum metabolomic profiling for 44 AML patients receiving treatment based on ATRA and valproic acid combined with low-dose cytotoxic drugs (cytarabine, hydroxyurea, 6-mercaptopurin) which identified 886 metabolites. When comparing pretreatment samples from responders and non-responders, metabolites mainly belonging to amino acid and lipid (i.e., fatty acid) pathways were altered. Furthermore, patients with rapidly progressive disease showed an extensively altered lipid metabolism. Both ATRA and valproic acid monotherapy also altered the amino acid and lipid metabolite profiles; however, these changes were only highly significant for valproic acid treatment. Twenty-three metabolites were significantly altered by seven-day valproic acid treatment (

Topics: Aged; Aged, 80 and over; Amino Acids; Cytarabine; Drug Therapy; Female; Humans; Hydroxyurea; Leukemia, Myeloid, Acute; Lipid Metabolism; Male; Mercaptopurine; Metabolomics; Middle Aged; Treatment Outcome; Tretinoin; Valproic Acid

Topics: Autoimmune Diseases; Azathioprine; Humans; Leukemia, Myeloid, Acute; Mercaptopurine; Myelodysplastic Syndromes

Topics: Autoimmune Diseases; Azathioprine; Humans; Leukemia, Myeloid, Acute; Mercaptopurine; Myelodysplastic Syndromes

Topics: Animals; Antimetabolites, Antineoplastic; Cell Line, Tumor; Glutathione; Humans; Hyaluronan Receptors; Hyaluronic Acid; Leukemia, Myeloid, Acute; Mercaptopurine; Mice; Nanoparticles; Prodrugs; Renal Elimination; Tissue Distribution; Vinyl Compounds

Topics: Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Biomarkers, Tumor; Cyclophosphamide; Cytarabine; Daunorubicin; Down-Regulation; Humans; Leukemia, Myeloid, Acute; Mercaptopurine; Methotrexate; Mutation; Nuclear Pore Complex Proteins; Oncogene Proteins, Fusion; Prednisone; Prognosis; Translocation, Genetic; Up-Regulation; Vincristine

Therapy-related myeloid neoplasms are a potentially life-threatening consequence of treatment for autoimmune disease (AID) and an emerging clinical phenomenon.. To query the association of cytotoxic, anti-inflammatory, and immunomodulating agents to treat patients with AID with the risk for developing myeloid neoplasm.. This retrospective case-control study and medical record review included 40 011 patients with an International Classification of Diseases, Ninth Revision, coded diagnosis of primary AID who were seen at 2 centers from January 1, 2004, to December 31, 2014; of these, 311 patients had a concomitant coded diagnosis of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). Eighty-six cases met strict inclusion criteria. A case-control match was performed at a 2:1 ratio.. Odds ratio (OR) assessment for AID-directed therapies.. Among the 86 patients who met inclusion criteria (49 men [57%]; 37 women [43%]; mean [SD] age, 72.3 [15.6] years), 55 (64.0%) had MDS, 21 (24.4%) had de novo AML, and 10 (11.6%) had AML and a history of MDS. Rheumatoid arthritis (23 [26.7%]), psoriasis (18 [20.9%]), and systemic lupus erythematosus (12 [14.0%]) were the most common autoimmune profiles. Median time from onset of AID to diagnosis of myeloid neoplasm was 8 (interquartile range, 4-15) years. A total of 57 of 86 cases (66.3%) received a cytotoxic or an immunomodulating agent. In the comparison group of 172 controls (98 men [57.0%]; 74 women [43.0%]; mean [SD] age, 72.7 [13.8] years), 105 (61.0%) received either agent (P = .50). Azathioprine sodium use was observed more frequently in cases (odds ratio [OR], 7.05; 95% CI, 2.35- 21.13; P < .001). Notable but insignificant case cohort use among cytotoxic agents was found for exposure to cyclophosphamide (OR, 3.58; 95% CI, 0.91-14.11) followed by mitoxantrone hydrochloride (OR, 2.73; 95% CI, 0.23-33.0). Methotrexate sodium (OR, 0.60; 95% CI, 0.29-1.22), mercaptopurine (OR, 0.62; 95% CI, 0.15-2.53), and mycophenolate mofetil hydrochloride (OR, 0.66; 95% CI, 0.21-2.03) had favorable ORs that were not statistically significant. No significant association between a specific length of time of exposure to an agent and the drug's category was observed.. In a large population with primary AID, azathioprine exposure was associated with a 7-fold risk for myeloid neoplasm. The control and case cohorts had similar systemic exposures by agent category. No association was found for anti-tumor necrosis factor agents. Finally, no timeline was found for the association of drug exposure with the incidence in development of myeloid neoplasm.

Topics: Aged; Aged, 80 and over; Arthritis, Rheumatoid; Autoimmune Diseases; Azathioprine; Case-Control Studies; Cyclophosphamide; Female; Humans; Immunosuppressive Agents; Incidence; Leukemia, Myeloid, Acute; Lupus Erythematosus, Systemic; Male; Mercaptopurine; Methotrexate; Middle Aged; Mitoxantrone; Mycophenolic Acid; Myelodysplastic Syndromes; Odds Ratio; Psoriasis; Retrospective Studies; Risk Factors; United States

We analyzed the effects of granulocyte colony-stimulating factor (G-CSF) on outcomes in 315 anthracycline-based induction chemotherapy-treated patients with non-M3 acute myelogenous leukemia (AML). Patients were classified as follows: no G-CSF administration during induction (no G-CSF group; 112 patients); administration immediately upon neutropenia onset (absolute neutrophil counts (ANC)<1000/μL), but before febrile neutropenia (preemptive group; 74 patients); and administration following febrile neutropenia development (therapeutic group; 129 patients). G-CSF users had a shorter time to ANC recovery than the no G-CSF group (p<0.001). The chemotherapy-induced febrile neutropenia (CIFN) duration was significantly shorter in the preemptive group than in other groups (p<0.001). The incidence of CIFN was not significantly different between preemptive and non-G-CSF users (84.8% versus 82.4%). Preemptive G-CSF administration modestly improved treatment-related mortality (TRM), compared with no G-CSF administration (p=0.076 in multivariate analysis). G-CSF administration did not affect relapse-free or overall survivals or the cumulative relapse incidence among the groups. In conclusion, preemptive G-CSF administration reduced CIFN duration and modestly improved TRM without affecting chemotherapy outcomes. These effects were not observed in the therapeutic group; therefore, initiation of G-CSF during induction therapy before the development of febrile neutropenia may be desirable.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anthracyclines; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy-Induced Febrile Neutropenia; Cyclophosphamide; Cytarabine; Daunorubicin; Female; Granulocyte Colony-Stimulating Factor; Humans; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Middle Aged; Mortality; Remission Induction; Republic of Korea; Retrospective Studies; Treatment Outcome; Young Adult

Individuals who are exposed to cytotoxic agents are at risk of developing therapyrelated myeloid neoplasms (t-MN). Cytogenetic findings of a neoplasm play an important role in stratifying patients into different risk groups and thus predict the response to treatment and overall survival.. A 59-year-old man was diagnosed with acute promyelocytic leukaemia. Following this, he underwent all-trans retinoic acid (ATRA) based chemotherapy and achieved remission. Four years later, the disease relapsed and he was given idarubicin, mitoxantrone and ATRA followed by maintenance chemotherapy (ATRA, mercaptopurine and methotrexate). He achieved a second remission for the next 11 years. During a follow-up later, his full blood picture showed leucocytosis, anaemia and leucoerythroblastic picture. Bone marrow examination showed hypercellular marrow with trilineage dysplasia, 3% blasts but no abnormal promyelocyte. Fluorescence in-situ hybridisation (FISH) study of the PML/RARA gene was negative. Karyotyping result revealed complex abnormalities and monosomal karyotype (MK). A diagnosis of therapy-related myelodysplastic syndrome/myeloproliferative neoplasm with unfavourable karyotypes and MK was made. The disease progressed rapidly and transformed into therapy-related acute myeloid leukaemia in less than four months, complicated with severe pneumonia. Despite aggressive treatment with antibiotics and chemotherapy, the patient succumbed to the illness two weeks after the diagnosis.. Diagnosis of t-MN should be suspected in patients with a history of receiving cytotoxic agents. Karyotyping analysis is crucial for risk stratification as MK in addition to complex aberrant karyotypes predicts unfavourable outcome. Further studies are required to address the optimal management for patients with t-MN.

Topics: Abnormal Karyotype; Antineoplastic Combined Chemotherapy Protocols; Humans; Idarubicin; In Situ Hybridization, Fluorescence; Karyotyping; Leukemia, Myeloid, Acute; Leukemia, Promyelocytic, Acute; Male; Mercaptopurine; Methotrexate; Middle Aged; Mitoxantrone; Neoplasm Recurrence, Local; Neoplasms, Second Primary; Tretinoin

We describe a patient diagnosed with acute myeloid leukemia (AML) and low activity of thiopurine methyltransferase (TPMT) who developed secondary myelodysplastic syndrome after treatment.. A 10-year-old boy presented with AML-M2 with t(8;21)(q22;q22) and genotyping revealing 3*B TPMT heterozygosity. The patient was treated according to the NOPHO-AML 2004 protocol. Two years after the treatment, the patient presented with neutropenia and thrombocytopenia. Bone marrow, including fluorescent in situ hybridization and retrospective aCGH analysis, verified therapy-related myelodysplastic syndrome with ring chromosome 6.. The clinical course of this patient raises the possibility that low-activity TPMT genotypes may influence 6TG toxicity in patients with AML and lead to an increased risk of developing secondary malignant neoplasms.

Topics: Antimetabolites, Antineoplastic; Child; Heterozygote; Humans; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Methyltransferases; Myelodysplastic Syndromes

For decades, maintenance chemotherapy has failed to improve the cure rate or prolong the survival of patients with acute myeloid leukemia (AML), other than those with acute promyelocytic leukemia. Immediately after the first complete remission following consolidation therapy was obtained, oral maintenance chemotherapy (daily 6-mercaptopurine and weekly methotrexate) was given and continued for two years in transplant-ineligible AML patients. Leukemia-free survival (LFS) and overall survival (OS) were studied and compared between these patients and the historical control group who did not receive maintenance therapy. Consecutive 52 transplant-ineligible AML patients were analyzed. Among these patients, 27 received oral maintenance chemotherapy. No significant difference was found in the patients' characteristics between the maintenance and the control groups. The median OS was 43 (95% CI, 19-67) and 19 (95% CI, 8-30) months in the maintenance and the control groups, respectively (P = 0.202). In the multivariate analysis, the presence of maintenance therapy was an independent prognostic factor for better OS (P = 0.021) and LFS (P = 0.024). Clinical benefit from maintenance chemotherapy was remarkable in older patients (≥ 60 yr) (P = 0.035), those with intermediate or unfavorable cytogenetics (P = 0.006), those with initial low blast count in peripheral blood (P = 0.044), and those receiving less than two cycles of consolidation therapy (P = 0.017). Maintenance oral chemotherapy as a post-remission therapy can prolong the survival of patients with AML who are not eligible for transplantation, particularly older patients, those with intermediate or unfavorable cytogenetics, those with initial low blast count, and those receiving less than two cycles of consolidation therapy.

Topics: Adolescent; Adult; Aged; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Disease-Free Survival; Female; Humans; Idarubicin; Leukemia, Myeloid, Acute; Maintenance Chemotherapy; Male; Mercaptopurine; Methotrexate; Middle Aged; Remission Induction; Treatment Outcome; Young Adult

Intensive chemotherapy for newly diagnosed acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS) is associated with significant treatment-related morbidity and mortality. Herein, we investigate how pretreatment characteristics relate to early adverse outcomes in such patients, studying 205 consecutive individuals receiving curative-intent induction chemotherapy with cytarabine and an anthracycline ("7 + 3"; n = 175) or a "7 + 3"-like regimen (n = 30). Among the entire cohort, baseline grade 4 neutropenia (i.e., absolute neutrophil count <500 cells/µL) was associated with development of fever (P = 0.04), documented infection (P < 0.0001), and bacteremia (P = 0.002) but not requirement for intensive care unit-level care; after exclusion of the 30 patients who received "7 + 3"-like induction, baseline grade 4 neutropenia remained associated with documented infection (P < 0.0001) and bacteremia (P = 0.0005). Among patients achieving a complete remission with the initial treatment cycle, grade 4 neutropenia was associated with delayed neutrophil count recovery (P < 0.0001). Low monocyte and lymphocyte counts at baseline were similarly associated with increased risk of documented infection or bacteremia. After adjustment for age, gender, disease type, cytogenetic/molecular risk, and performance status, the risk of fever, documented infection, or bacteremia was 1.87 (95% confidence interval: 1.04-3.34; P=0.04)-fold, 4.95 (2.20-11.16; P<0.001)-fold, and 3.14 (0.99-9.98; P=0.05)-fold higher in patients with initial grade 4 neutropenia. Together, our studies identify severe baseline neutropenia as a risk factor for infection-associated adverse events after induction chemotherapy and may provide the rationale for the risk-adapted testing of myeloid growth factor support in this high-risk AML/MDS patient subset.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Bacteremia; Blood Cell Count; Critical Care; Cyclophosphamide; Cytarabine; Daunorubicin; Febrile Neutropenia; Female; Granulocyte Colony-Stimulating Factor; Humans; Immunocompromised Host; Infections; Kaplan-Meier Estimate; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Middle Aged; Myelodysplastic Syndromes; Proportional Hazards Models; Remission Induction; Retrospective Studies; Young Adult

This paper reviews the development of therapy for acute myelogenous leukemia that in 1973 led to the regimen of 7days of continuous intravenous arabinosylcytosine (cytarabine) and the first 3 concurrent days of intravenous daunorubicin, given the nickname "7+3." The state of leukemia treatment in the 1950s, 1960s and early 1970s is reviewed, the discovery of the two drugs in question described, and the introduction of clinical trials to reach an optimal regimen for their use delineated. During the 1950s, following World War Two and after a period of civil reconstitution, a national effort, facilitated by the U.S. Congress and federal investments in the National Cancer Institute, was initiated to enhance cancer therapy in the United States. The development of mouse models of leukemia and advances in understanding the structure and function of DNA and RNA and the process of cell proliferation provided new targets for drug development and new concepts for their use. The year, 2013, marks the 40th year that this protocol, 7+3, is the method of induction of remission for most patients with acute myelogenous leukemia. Its inadequacies also are made clear. Many patients with the disease die soon after diagnosis, and patients who have more unfavorable oncogenetic subtypes, intrinsically drug resistant cells, and greater intolerance to therapy make up the vast majority of the affected and few are cured. It is evident to all that new paradigms are needed if acute myelogenous leukemia is to be subdued in most patients with the disease.

Topics: Adolescent; Adult; Aged; Animals; Antineoplastic Combined Chemotherapy Protocols; Cancer Care Facilities; Case Management; Child; Clinical Trials as Topic; Cyclophosphamide; Cytarabine; Daunorubicin; Dogs; Drug Resistance, Neoplasm; Drug Screening Assays, Antitumor; Female; Forecasting; France; Haplorhini; Hematology; History, 20th Century; History, 21st Century; Humans; Leukemia, Myeloid, Acute; Male; Medical Oncology; Mercaptopurine; Middle Aged; National Institutes of Health (U.S.); Rats; Remission Induction; United States

Topics: Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Chromosomes, Human, Pair 6; Chromosomes, Human, Pair 9; Combined Modality Therapy; Cranial Irradiation; Cytarabine; Daunorubicin; Erythropoiesis; Etoposide; Female; Humans; Leukemia, Myeloid, Acute; Maintenance Chemotherapy; Mercaptopurine; Methotrexate; Middle Aged; Neoplasms, Second Primary; Oncogene Proteins, Fusion; Pancytopenia; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma; Translocation, Genetic; Vincristine

Topics: Adult; Aminoglycosides; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Clone Cells; Combined Modality Therapy; Consolidation Chemotherapy; Cytarabine; Daunorubicin; Gemtuzumab; Humans; Leukemia, Myeloid, Acute; Lymphocyte Transfusion; Male; Mercaptopurine; Myeloid-Lymphoid Leukemia Protein; Neoplastic Stem Cells; Oncogene Proteins, Fusion; Prednisolone; Recurrence; Remission Induction; Reoperation; Time Factors; Transplantation, Homologous; Vincristine

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Cytarabine; Daunorubicin; Humans; Leukemia, Myeloid, Acute; Mercaptopurine

Topics: Antimetabolites, Antineoplastic; Crohn Disease; Female; Humans; Leukemia, Myeloid, Acute; Mercaptopurine; Middle Aged; Treatment Outcome

Topics: Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Child; Cyclophosphamide; Cytarabine; Daunorubicin; Humans; Leukemia, Myeloid, Acute; Magnetic Resonance Imaging; Male; Mercaptopurine; Methotrexate; Prednisone; Radiography; Vincristine; Wernicke Encephalopathy

Thiopurines are effective immunosuppressants and anticancer agents, but intracellular accumulation of their active metabolites (6-thioguanine nucleotides, 6-TGN) causes dose-limiting hematopoietic toxicity. Thiopurine S-methyltransferase deficiency is known to exacerbate thiopurine toxicity. However, many patients are highly sensitive to thiopurines for unknown reasons. We show that multidrug-resistance protein 4 (Mrp4) is abundant in myeloid progenitors and tested the role of the Mrp4, an ATP transporter of monophosphorylated nucleosides, in this unexplained thiopurine sensitivity. Mrp4-deficient mice experienced Mrp4 gene dosage-dependent toxicity caused by accumulation of 6-TGNs in their myelopoietic cells. Therefore, Mrp4 protects against thiopurine-induced hematopoietic toxicity by actively exporting thiopurine nucleotides. We then identified a single-nucleotide polymorphism (SNP) in human MRP4 (rs3765534) that dramatically reduces MRP4 function by impairing its cell membrane localization. This SNP is common (>18%) in the Japanese population and indicates that the increased sensitivity of some Japanese patients to thiopurines may reflect the greater frequency of this MRP4 SNP.

Topics: Alleles; Animals; Cell Membrane; Cells, Cultured; Cytoprotection; Drug Resistance, Neoplasm; Hematologic Diseases; Hematopoiesis; Humans; Leukemia, Myeloid, Acute; Membrane Transport Proteins; Mercaptopurine; Mice; Mice, Knockout; Models, Biological; Multidrug Resistance-Associated Proteins; Polymorphism, Single Nucleotide; Purines; Sulfhydryl Compounds; Survival Analysis; Tissue Distribution

Between January 2001 and December 2003, 67 patients with acute leukemia were evaluated prospectively for hemostatic abnormality at presentation, of which 43 (64.2%) had acute lymphoblastic leukemia and 24 (35.8%) had acute myelogenous leukemia. At presentation, 27 patients (40.3%) had bleeding manifestations. Thrombocytopenia was present in 57 patients (85%), and 33(49.3%) had some abnormality of global coagulation markers. Disseminated intravascular coagulation was defined by International Society of Thrombosis and Hemostasis criteria. Disseminated intravascular coagulation was more often associated with bleeding manifestations in acute myelogenous leukemia cases than in acute lymphoblastic leukemia cases. Two patients presented disseminated intravascular coagulation on day 7 of chemotherapy, without any bleeding manifestations. Four of 15 evaluated cases who had a bleeding or infection complication after day 7 of induction therapy also had disseminated intravascular coagulation. It is recommended that all patients with leukemia be investigated for disseminated intravascular coagulation at presentation.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Child; Child, Preschool; Cyclophosphamide; Cytarabine; Disseminated Intravascular Coagulation; Female; Humans; Incidence; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Methotrexate; Middle Aged; Partial Thromboplastin Time; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prednisone; Prospective Studies; Remission Induction; Vincristine

Topics: Antimetabolites, Antineoplastic; Chemical and Drug Induced Liver Injury; Cholagogues and Choleretics; Humans; Leukemia, Myeloid, Acute; Liver Function Tests; Male; Mercaptopurine; Middle Aged; Ursodeoxycholic Acid

Fifty-seven patients with acute myelogenous leukemia (AML) received the following treatment in our hospital between May 1992 and April 2005. Group A: combination of enocitabine, daunorubicin, 6-mercaptopurine riboside and prednisolone (BHAC-DMP) for remission induction, BHAC-DMP or idarubicin (IDR)+cytarabine (Ara-C) for first consolidation, combination of prednisolone, Ara-C, mitoxantrone and etoposide (PAME) for second consolidation, and PAME for late intensification; Group B: IDR+Ara-C for remission induction, PAME for first consolidation, and high-dose Ara-C+mitoxantrone for second consolidation; Group C (acute promyelocytic leukemia, APL) : all-trans retinoic acid (ATRA) for remission induction, BHAC-DMP or IDR+Ara-C for first consolidation, and PAME for second consolidation. The complete remission (CR) rate was 77% in Group A, 76% in Group B, and 71% in Group C. Five-year relapse-free survival rate of the CR patients was 35% in Group A, 49% in Group B, and 70% in Group C. All of the patients had severe neutropenia, but the number of infectious death was small. A short duration treatment with intensive consolidation therapy was effective for patients with AML and improved their quality of life (QOL).

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Daunorubicin; Drug Administration Schedule; Etoposide; Evidence-Based Medicine; Female; Humans; Idarubicin; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Middle Aged; Mitoxantrone; Prednisolone; Prednisone; Quality of Life; Retrospective Studies; Survival Rate; Vincristine

We report here a 71 year-old female presenting with acute myeloblastic leukemia (FAB-M1) after treatment of essential thrombocythemia with Vercyte. Conventional cytogenetic techniques showed a complex karyotype, 44,XX,-5,-7,-11,add(11)(q23),-14,+mar,+r. The use of several fluorescent in situ hybridizations (FISH) lead to the identification of these complex rearrangements. The marker was found to be tricentric, with pericentromeric material of chromosome 7 inserted in the short arm of chromosome 5, resulting in monosomy 5q and 7q. The derivative chromosome 11 was dicentric and had subtelomeric sequences of 11p on both ends; several copies of the MLL gene were located in two different regions separated by a centromere of chromosome 11. Twenty-one cases, including ours, of myelodysplastic syndromes and acute myelogenous leukemia with MLL amplification present in hsr or dmin were found in the literature. Most of these patients shared some characteristics: they were old, they had de novo acute myeloid leukemia (AML) with a complex karyotype and a short survival, 90% of them having also a del(5q). Therefore, the simultaneous presence of MLL amplification and del(5q) appears to be a nonrandom association that could be the signature of AML in elderly patients with a poor prognosis.

Topics: Aged; Chromosome Deletion; Chromosomes, Human, Pair 11; Chromosomes, Human, Pair 5; Chromosomes, Human, Pair 7; Cytogenetic Analysis; Fatal Outcome; Female; Gene Amplification; Histone-Lysine N-Methyltransferase; Humans; In Situ Hybridization, Fluorescence; Karyotyping; Leukemia, Myeloid, Acute; Mercaptopurine; Myeloid-Lymphoid Leukemia Protein; Pipobroman; Prognosis; Sensitivity and Specificity; Thrombocytosis

Protein C, protein S, and antithrombin III were measured in 35 patients with acute leukemia (13 with AML and 22 with ALL). Low levels of proteins C and S were present in 15 (42.9%) and 20 (57.1%) patients, respectively, and 6 patients had low levels of antithrombin (ATIII). Seven patients also had DIC at presentation. There were no significant differences in the levels of protein C, protein S, and ATIII in patients with or without DIC. Twenty patients were available for re-evaluation at the end of induction therapy. The low levels of protein C and ATIII found at diagnosis had risen to normal levels at the end of the induction therapy, while low =levels of protein S remained in 75% of the patients. One patient with low protein C at presentation developed myocardial infarction on day 15, and another patient died of progressive neuropathy. No other thrombotic manifestations were seen. Whether the low protein C, protein S, or antithrombin levels predispose patients with acute leukemia to thrombosis in the absence of DIC is not known.

Topics: Antineoplastic Combined Chemotherapy Protocols; Antithrombin III; Asparaginase; Cyclophosphamide; Cytarabine; Disseminated Intravascular Coagulation; Female; Humans; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Methotrexate; Myocardial Infarction; Peripheral Nervous System Diseases; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Predictive Value of Tests; Prednisone; Protein C; Protein S; Thrombosis; Vincristine

To explore the effect of the treatment for long-term disease-free survival (DFS) of post-remission patients with acute myeloid leukemia (AML).. Twenty-nine AML patients with completely remission (CR) and 17 with partial remission (PR) were treated with Chinese medicine, Longchan Cigu Decoction 1 dose per day and Lingxiong Piaoling Powder 7 doses per month, and combined with DA or HA regimen of chemotherapy one course per year. Patients peripheral blood picture, bone marrow smear, biopsy and human leukocyte antigen DR (HLA-DR) cells were examined before and after treatment, and their disease-free survival (DFS) was followed up.. After treated with above mentioned treatment for 2 months, percentage of patients with normal peripheral blood count increased, including patients with WBC > or = 4.0 x 10(9)/L raised from 46% to 70%, with Hb > or = 120 g/L from 17% to 46% and with PLT > or = 100 x 10(9)/L from 63% to 85%; nucleated cell volume in bone marrow increased from 35.83 +/- 28.42% to 60.46 +/- 17.73% (P < 0.01); HLA-DR cell was also increased significantly from 10.55 +/- 4.95% to 14.84 +/- 4.94%, (P < 0.01); while the residual leukemia cells were not increased in one year, from 5.90 +/- 5.09% before and 5.82 +/- 2.42% after treatment (P > 0.05). The maximal DFS in patients was 123 months. The 3-year survival rate was 64.15 +/- 1.96% and 5-year survival rate was 51.19 +/- 16.25%.. The integrative Chinese and western medicine treating program used in this study is beneficial for the long-term treatment of AML patients after complete remission.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Child; Child, Preschool; Disease-Free Survival; Drug Therapy, Combination; Drugs, Chinese Herbal; Female; Humans; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Methotrexate; Middle Aged; Phytotherapy; Remission Induction; Survival Rate

A 71-year-old man was admitted to our hospital because of right lower abdominal pain. He was suspected of having acute appendicitis and soon after admission, appendectomy was performed. Macroscopically, the appendix was greatly swollen and reddened, but had no abscess. Microscopically, polymorphonuclear leukocytes were not found, but diffuse infiltration of atypical cells was observed. Examination of a bone marrow aspirate revealed 74% blasts that were peroxidase stain positive. We diagnosed acute myelogenous leukemia (FAB classification, M2). He received induction chemotherapy, but died 49 days after admission. Leukemic cell infiltration of the appendix is rare and acute appendicitis as the initial manifestation of leukemia is even rarer.

Topics: Aged; Antigens, CD; Antigens, Neoplasm; Antineoplastic Combined Chemotherapy Protocols; Appendectomy; Appendicitis; Appendix; Combined Modality Therapy; Cytarabine; Daunorubicin; Disease Progression; Fatal Outcome; Humans; Idarubicin; Immunophenotyping; Leukemia, Myeloid, Acute; Leukemic Infiltration; Male; Mercaptopurine; Sarcoma, Myeloid

Topics: Adult; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Female; Humans; Leukemia, Myeloid, Acute; Leukemia, Promyelocytic, Acute; Mercaptopurine; Methotrexate; Myelodysplastic Syndromes; Neoplasms, Second Primary; Prednisone; Remission Induction; Tretinoin; Vincristine

A 38-year old man was transmitted to our hospital because of his pneumonia and disconsciousness. Laboratory data showed leukocytosis (32,500/microliter), mild anemia, and decreased platelet count (6.7 x 10(4)/microliter). The bone marrow aspiration revealed the presence of 40% blastoid cells and cytogenetic study showed abnormal karyotype, 45, X, -Y, t(8; 21) (q22; q22), indicating acute myeloid leukemia (AML, M2). Furthermore, on the microscopic observation, cell fragments resembling giant platelets were observed which were positive for myeloperoxidase, and several fragments connected with abnormal promyelocytes through thin cytoplasm. These results suggested these cell fragments may be produced from abnormal promyelocytes in this case.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Daunorubicin; Granulocytes; Humans; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Platelet Count; Prednisolone; Remission Induction

A retrospective analysis was performed on 76 consecutive elderly patients with acute leukemia aged 60 years or more (48 men, 28 women). Forty patients were 60-69 years old, 28 were 70-79 years old and 8 were > or = 80 years old. There were 55 patients with acute myelogenous leukemia (AML), 13 acute lymphoblastic leukemia (ALL) and 8 AML from myelodysplastic syndrome (MDS/AML). Patients were treated with the JALSG protocol, CAG regimen, or low-dose Ara-C regimen for AML, and DVP/M-CHOP protocol for ALL. The complete remission (CR) rates were 52.7% (29 of 55) in AML, 61.5% (8 of 13) in ALL, and 0% in MDS/AML. The median CR durations were 226, 85, 0 days, and the median survivals were 204, 177, 99 days, respectively. CR rates were 65.3% for the JALSG protocol, 62.5% for the CAG regimen and 25.0% for low-dose Ara-C regimen. According to age, CR was obtained 62.5% in patients aged 60-69 years and 33.3% in patients over 70 years old. Our results indicated that patients aged 60-69 years should be treated with intensive chemotherapy.

Topics: Aclarubicin; Aged; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Cytarabine; Daunorubicin; DNA; Female; Granulocyte Colony-Stimulating Factor; Humans; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Methotrexate; Middle Aged; Myelodysplastic Syndromes; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prednisolone; Retrospective Studies; Vincristine

A 26-year-old man, diagnosed with acute myelogenous leukemia had multiple inflammatory pseudotumors (IPT) in the liver. The patient presented complete remission after remission induction therapy, and then showed right upper quadrant discomfort and intermittent fever. An ultrasonography disclosed multiple hypoechoic nodules in the liver. A biopsy of the nodules showed focal liver cell necrosis with scant inflammatory cells, compatible with IPT. After several courses of chemotherapy, the nodules in the liver increased. The second liver biopsy of the nodule showed fibrosis. Multiple IPTs in the liver should be distinguished from abscess and metastatic nodules.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Biopsy, Needle; Cytarabine; Daunorubicin; Diagnosis, Differential; Granuloma, Plasma Cell; Humans; Leukemia, Myeloid, Acute; Liver Abscess; Liver Diseases; Liver Neoplasms; Magnetic Resonance Imaging; Male; Mercaptopurine; Prednisolone; Tomography, X-Ray Computed

A 65-year-old man with Crohn's disease died of acute myeloblastic leukemia after treatment for 11.8 years with 6-mercaptopurine, 1.5 mg/kg/day (100 mg/day). On cytogenetic analysis, most of the malignant bone marrow cells had deletion of chromosome 7, the most frequently reported cytogenetic abnormality in chemotherapy-related acute leukemia. This finding, together with previous reports of acute leukemia and other malignancies following prolonged treatment with azathioprine or 6-mercaptopurine for nonmalignant conditions including inflammatory bowel disease, indicates that long-term use of these drugs for inflammatory bowel disease may increase the risk of malignancy. However, the magnitude of the risk is unknown.

Topics: Aged; Chromosome Deletion; Chromosomes, Human, Pair 7; Crohn Disease; Humans; Immunosuppressive Agents; Leukemia, Myeloid, Acute; Male; Mercaptopurine

A 18-year old female with acute myelogenous leukemia (AML), M2 had translocation: t(6;9) (p23; q34). The patient entered into hematological complete remission after two courses of BHAC-DMP chemotherapy with disappearance of cytogenetic abnormality. However, minimal residual disease (MRD) detected with DEK/CAN chimeric m-RNA by reverse transcription polymerase chain reaction (RT-PCR) was continuously observed, although decreased quantitatively, following several courses of consolidation and intensification chemotherapies. MRD was detected also in the harvested peripheral blood stem cells (PBSC). Leukemia relapsed with the reappearance of t(6;9) 2 months after the subsequent peripheral blood stem cell transplantation (PBSCT). Leukemia became refractory to chemotherapy, and the patient died 5 months thereafter.

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Chromosomes, Human, Pair 6; Chromosomes, Human, Pair 9; Combined Modality Therapy; Cytarabine; Daunorubicin; Etoposide; Female; Hematopoietic Stem Cell Transplantation; Humans; Leukemia, Myeloid, Acute; Mercaptopurine; Mitoxantrone; Neoplasm, Residual; Oncogene Proteins; Oncogene Proteins, Fusion; Polymerase Chain Reaction; Prednisolone; Recombinant Fusion Proteins; RNA, Messenger; Translocation, Genetic

We report a case of 53-year-old man with acute myelogenous leukemia (M2) showing a karyotype of t(7;11) (p15;p15), del(10) (q11;q12), who was complicated with perforation of a duodenal ulcer during the antileukemic chemotherapy using behenoyl ara-C, daunorubicin, 6-mercaptopurine and prednisolone. As his bone marrow still showed high cell density and leukemic proliferation at the time of intestinal perforation, the therapeutic regimen was changed to a combination of behenoyl are-C and mitoxantrone, and daily rhG-CSF was concurrently administered for the purpose of early establishment of bone marrow hypoplasia. On the 8th day after the therapeutic regimen had been changed, his bone marrow became nearly aplastic, and complete remission was obtained on the 24th day. This case may indicate that the concurrent administration of cell-cycle specific antileukemic drugs and rhG-CSF is available for AML patients with emergent need of leukemic cell reduction.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Cytarabine; Daunorubicin; Duodenal Diseases; Granulocyte Colony-Stimulating Factor; Humans; Intestinal Perforation; Karyotyping; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Middle Aged; Prednisolone; Recombinant Proteins; Remission Induction

We studied fifteen patients older than 80 years of age with acute myelogenous leukemia (AML) treated between 1984 and 1996. Among 15 cases of AML including 7 de novo cases and 8 from myelodysplastic syndrome (MDS) or hypoplastic leukemia, 14 patients had complications, including cardiovascular disease, diabetes mellitus or other malignancies. Although patients with de novo AML showed high peripheral WBC counts and higher cellularity of bone marrow than those from MDS or hypoplastic leukemia, it was difficult in some cases to distinguish these types of AML from hematological findings. Of the 6 AML cases, three had entered complete remission (CR) by a standard dose of combination chemotherapy (BHAC-DMP). One CR patient has had CR for more than 9 years now with good QOL. Among the 3 patients treated by low-dose Ara-C, one attained CR but only for a short period. Four other patients received BRM, such as G-CSF or Ubenimex, and 2 patients died without chemotherapy. Since AML at more than 80 years of age is a highly heterogenous disease, it would be reasonable to give antileukemic agents according to the individual patient's condition.

Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Daunorubicin; Female; Humans; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Prednisolone; Quality of Life; Remission Induction

A 28 year-old woman in the 26th week of pregnancy was admitted to our hospital on February 6, 1993, because of anemia and thrombocytopenia. On admission, her hemoglobin was 8.2 g/dl, platelet count 6.3 x 10(4)/microliter, and WBC 6,300/microliter with 43% blasts. The bone marrow examination showed hyperplastic bone marrow with 38.8% blasts. She was diagnosed as having 8;21 translocation acute myelocytic leukemia (M2). In the 30th week of pregnancy, she gave birth to a 1449 g male infant by induction delivery. After DCMP therapy, complete remission was obtained. She has been in complete remission for 32 months and her child is growing healthy after overcoming an underweight condition due to premature birth, respiratory distress syndrome, circulation insufficiency and hyperbilirubinemia. This case suggests that in the event of second trimester pregnant patients with acute leukemia, we should wait for the proper time at which successful delivery can be expected, and then intensified remission induction chemotherapy should be carried out after the delivery.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Chromosomes, Human, Pair 21; Chromosomes, Human, Pair 8; Cytarabine; Daunorubicin; Female; Humans; Infant, Newborn; Labor, Obstetric; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Prednisolone; Pregnancy; Pregnancy Complications, Neoplastic; Remission Induction; Translocation, Genetic

Ubenimex (Bestatin, Ubx) has been shown to have anti-tumor activity and immuno-modulating activities. Ubx has been used in immuno-therapy in combination with remission maintenance chemotherapy after induction of complete remission for adult acute non-lymphocytic leukemia (ANLL, AML). Daunomycin (DNR), arabinosylcytosine (Ara-C) and 6-mercaptopurine (6-MP) are used for the standard chemotherapy for ANLL. It is, however, believed that emergence of resistant cells to chemotherapy cause minimal residual leukemia resulting in poor prognosis. Ubx has been administered in combination with these chemotherapeutic agents. We examined the combinatorial effect of Ubx with DNR, Ara-C, 6-MP and etoposide on K562 leukemic cell line and the chemotherapeutic agent resistant cells derived from K562 cell line. Ubx showed growth inhibitory effects on these cell lines. A synergistic effect was observed on growth inhibition and with colony formation of parent k562 cell line when DNR and Ubx were used in combination. A combination of Ubx with Ara-C or etoposide showed additional effects on parent cells and other resistant cell lines. The combined growth inhibitory effect of 6-MP and Ubx was stronger than the effect of 6-MP alone. These results show that Ubx has a direct growth inhibitory effect on leukemic cells and additional or synergistic effects are obtained on K562 leukemic cell line and on chemotherapeutic agent resistant cells derived from the K562 cell line when Ubx is used combination with the above chemotherapeutic agents.

Topics: Antibiotics, Antineoplastic; Antineoplastic Agents; Cell Division; Cytarabine; Daunorubicin; Depression, Chemical; Drug Combinations; Drug Resistance, Neoplasm; Drug Synergism; Humans; Leucine; Leukemia, Myeloid, Acute; Mercaptopurine; Tumor Cells, Cultured

The fungus Fusarium moniliforme causes fusariosis, which can be invasive and fatal in immunocompromised patients. We report a case of oral Fusarium infection in a granulocytopenic patient with acute myelogenous leukemia who developed necrotic ulceration of the gingiva, extending to the alveolar bone, but was otherwise free of any active systemic lesions. Fusarium moniliforme was identified, by histopathology and culture, to be present in the lesion and was deduced to be the causative organism for this invasive oral infection.

Topics: Acute Kidney Injury; Aged; Agranulocytosis; Amphotericin B; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Epirubicin; Etoposide; Fatal Outcome; Fusarium; Gingival Diseases; Humans; Immunocompromised Host; Leukemia, Myeloid, Acute; Male; Maxillary Diseases; Mercaptopurine; Mycoses; Necrosis; Prednisolone; Ulcer; Vindesine

We report a case of AML with diabetes insipidus (DI). A 68-year-old female was admitted to our hospital because of fever and leukocytosis. The WBC was 197,000/microliter with 98% blasts positive for myeloperoxidase, CD33, CD34 and HLA-DR. While, on admission, urine volume was more than 6 liters daily. Blood vasopressin level was 0.3 microgram/ml. The patient was diagnosed as having AML with DI. By chemotherapy consisting of BHAC, DNR, 6-MP and PSL and intrathecal administration of AraC, MTX and PSL, and nasal drip of DDAVP, complete remission was attained and the urine volume was reduced to normal. Finally DDAVP became unnecessary. Although the exact cause of DI cannot be ascertained, rapid increase of leukemic blasts and leukostasis in small vessels might be associated with hypothalamus-pituitary system damage. Reportedly, DI is a rare complication of leukemia and administration of DDAVP could be halted in only two patients with leukemia and DI.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Daunorubicin; Deamino Arginine Vasopressin; Diabetes Insipidus; Female; Humans; Leukemia, Myeloid, Acute; Mercaptopurine; Prednisolone; Renal Agents

A 54-year-old man was admitted with pneumonia and pancytopenia (WBC 400/microliters, RBC 297 x 10(4)/microliters, Hb 10.1g/dl, Plt 5.6 x 10(4)/microliter). Bone marrow aspiration revealed a proliferation of leukemic cells (61.6%) and led the diagnosis of AML (M2). Although no antileukemic agent had been administered previously, the combination therapy of antimicrobials and rhG-CSF for the infection not only improved pneumonia, but also induced a complete remission of AML. The short-term remission was followed by the first relapse of AML, in spite of the continuous administration of rhG-CSF. The abnormal karyotype (47, XY, +8) shown in the chromosomal analysis of the bone marrow cells at admission remained on the first remission. The second complete remission was induced by combination chemotherapy (BHAC-DMP), and the chromosomal analysis at this time showed a normal karyotype. These findings suggested that the first remission of AML in this case was caused mainly by the maturation induction effect of rhG-CSF on the leukemic cells, however, the possibility of the spontaneous remission in this case also remained.

Topics: Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Daunorubicin; Granulocyte Colony-Stimulating Factor; Humans; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Middle Aged; Pancytopenia; Pneumonia; Prednisolone; Recombinant Proteins; Remission Induction

This report documents the acute toxicity of anti-leukemic chemotherapy on the fetus in utero by umbilical blood sampling. A patient with acute myelocytic leukemia diagnosed at the 23rd week of gestation received combination chemotherapy, and carried the pregnancy to successful delivery at the 34th week. During the course of pregnancy, the fetal condition was evaluated by serial real time sonograms and umbilical blood sampling through cordocentesis. Fetal hematopoiesis was preserved against maternal chemotherapeutic agents, and no developmental abnormalities were observed. This is the first attempt to evaluate the acute effects of chemotherapeutic agents on the fetus in utero by real time umbilical cord sampling.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Daunorubicin; Female; Fetal Blood; Fetal Growth Retardation; Fetus; Humans; Infant, Newborn; Leukemia, Myeloid, Acute; Mercaptopurine; Prednisolone; Pregnancy; Pregnancy Complications, Neoplastic; Ultrasonography, Prenatal

Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Cytarabine; Daunorubicin; Diagnosis, Differential; Doxorubicin; Female; Granulocyte Colony-Stimulating Factor; Granulocytes; Humans; Leukemia, Myeloid, Acute; Leukocyte Count; Mercaptopurine; Middle Aged; Neoplasm Invasiveness; Prednisolone; Prednisone; Recombinant Proteins; Uterine Cervical Neoplasms; Vincristine

Thirty-four children with diagnosed cases of acute leukemias and being treated with cytotoxic chemotherapy at St James' Hospital, Leeds, were followed for between 6 months and 1 year to determine the changes in their oral microflora. They were examined before treatment commenced and then at monthly intervals. Swabs were taken from the oral cavity to test for the presence or absence of bacteria and Candida. Saliva samples were also used to assess the levels of Streptococcus mutans in the mouth. Sensitivity tests were carried out to assess the effect of the cytotoxic agents on the oral flora. All children received prophylactic nystatin and chlorhexidine gluconate mouthrinses four times daily for the whole period of the study. There was significant difference (p < 0.0001) for counts of S. mutans at different treatment stages. Sensitivity tests showed that S. mutans was sensitive to the cytotoxic drug daunorubicin, and this drug was probably responsible for the fall in S. mutans counts. A significant difference was also found in the types of bacteria isolated between the study and reference groups, but there was no change in the composition of the flora in the study group during treatment. These bacteria were also found to mirror those cultured from routine blood samples in children with acute leukemia.

Topics: Adolescent; Analysis of Variance; Anti-Bacterial Agents; Antifungal Agents; Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Bacterial Infections; Candida albicans; Candidiasis, Oral; Chi-Square Distribution; Child; Child, Preschool; Chlorhexidine; Colony Count, Microbial; Cytarabine; Daunorubicin; Etoposide; Female; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Infant; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Methotrexate; Mouth; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prednisolone; Streptococcus mutans; Thioguanine; Trimethoprim, Sulfamethoxazole Drug Combination; Vincristine

We report patients who were treated for non-Hodgkin's lymphoma (NHL) or Ki-1 antigen-positive (Ki-1) lymphoma with a T-8801 protocol that included etoposide (VP-16) and behenoylcytosine arabinoside.. Secondary acute myeloid leukemia (AML) developed in 5 of 38 NHL and Ki-1 lymphoma patients, and the cumulative risk at 4 years was 18.4%. The median time from the initiation of the chemotherapy to the development of AML was 21 months (range, 13-30). Four patients had a FAB M5 morphology, and one had FAB M2. In four of five examined cases, chromosomal alterations involving the long arm of chromosome 11 were demonstrated at the time of development of AML. None of the 46 NHL patients who we treated with another protocol (B-8801), using significantly higher cumulative doses of VP-16 than in the case of the patients with T-8801 and a different schedule of VP-16 administration, developed secondary AML.. The risk of secondary AML possibly related to the use of VP-16 given twice weekly.

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Asparagine; Child; Child, Preschool; Chromosome Aberrations; Chromosomes, Human, Pair 11; Cyclophosphamide; Cytarabine; Doxorubicin; Etoposide; Female; Follow-Up Studies; Humans; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Life Tables; Lymphoma, Non-Hodgkin; Male; Mercaptopurine; Methotrexate; Neoplasms, Second Primary; Risk; Vincristine

A case of acute non-lymphocytic leukemia who relapsed 7 years after the first remission is reported. The leukemic cells at onset had mature monocytic features with positive reactions for anti-CD14 antibody and alpha-NBE staining. By contrast, leukemic cells at relapse showed distinct morphological features from those at onset and lost their monocytic characters. No karyotypic abnormalities were found, but we could not exclude the possibility of secondary leukemia induced by the initial anti-leukemic chemotherapy.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Daunorubicin; Humans; Kidney Neoplasms; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Neoplasms, Second Primary; Prednisolone

We describe an unusual case of disseminated subcutaneous abscesses caused by Nocardia asteroides in a 17-year-old female with AML undergoing allogeneic BMT. She was receiving immunosuppressive therapy with CYA and a corticosteroid for acute GVHD, and maintenance therapy with ganciclovir for interstitial pneumonia (IP) caused by CMV, but was not neutropenic. The subcutaneous abscesses spread from the primary infection on her right anterior leg to both thighs, the left buttock, both upper arms, the left forearm and right shoulder, indicating hematogenous dissemination. Nocardia asteroides was identified from biopsy material in culture. The patient was successfully treated with a combination of trimethoprim/sulfamethoxazole (TMP/SMX) and minocycline, given for 3 months. The possibility of nocardiosis should be considered in the differential diagnosis of such patients.

Topics: Abscess; Adolescent; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Purging; Bone Marrow Transplantation; Combined Modality Therapy; Cytarabine; Daunorubicin; Female; Humans; Immunocompromised Host; Incidence; Leukemia, Myeloid, Acute; Mercaptopurine; Neutropenia; Nocardia asteroides; Nocardia Infections; Opportunistic Infections; Prednisolone; Remission Induction; Skin Diseases, Infectious

We made a retrospective study of 44 patients with acute non-lymphocytic leukemia (ANLL) and 14 patients with acute lymphocytic leukemia (ALL) admitted to our hospital from September 1984 to May 1991. The complete remission (CR) rate of ANLL was 90.9%, against 85.7% for ALL. The 5-year survival of ANLL was 50.7%, and that of ANLL under age 60 years was 70.3%. The 2-year median survival of ALL was 35.1%. These results were obtained with response-oriented individualized therapy, and intensive chemotherapy with a view to eradication of residual leukemic cells. Eight elderly patients with ANLL were treated with cytosine arabinoside in low doses. Complete remission was achieved in 6 patients, but these cases relapsed. These treatments should be reconsidered for long CR duration. Our schedules of response-oriented individualized therapy were too flexible to apply at another institute so they should be arranged for general application.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Daunorubicin; Drug Administration Schedule; Female; Humans; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Middle Aged; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prednisolone; Remission Induction; Retrospective Studies; Survival Rate; Treatment Outcome

Intensive induction chemotherapy was applied to 25 patients with acute myelogenous leukemia by continuing drugs (daunorubicin, behenoyl-cytosine arabinoside, 6-mercaptopurine and prednisolone) until the achievement of severe bone marrow aplasia (leukemic cells less than 1,000/microliters). Complete remission (CR) was achieved in 18 (72%). Numbers of partial remission and an early death were 5 (20%) and 2 (8%), respectively. Although median nadirs of white blood cells (WBC) and platelet counts (Pl) (205/microliters and 8,200/microliters, respectively) were remarkably low, recovery of WBC (over 1,000/microliters) and Pl (over 50,000/microliters) were achieved in 23.8 and 24.5 days, after an initiation of the chemotherapy. Sepsis was a most frequently observed complication during induction stage and a duration of fever was 2-48 days (median 15). Median duration of CR was 22.9 months. Unexpectedly, 11 of 17 CR (except one with bone marrow transplanted) relapsed after 4.2-41.4 months (median; 9.4), but 6 (35.3%) still remain in first CR for 30.5-72.9 months (median; 51.4). A long-term survival might be obtained by intensifying induction chemotherapy in about one fourth of patients, but the intensification or application of non-cross resistant anti-leukemic agents in post-remission therapy may be required to avoid relapses even if induction is intensified.

Topics: Administration, Oral; Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Cytarabine; Daunorubicin; Drug Administration Schedule; Female; Humans; Infusions, Intravenous; Injections, Intravenous; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Middle Aged; Prednisolone; Remission Induction; Sepsis; Survival Rate

To investigate the physiologic role of macrophage colony-stimulating factor (M-CSF) in hematological recovery from bone marrow hypoplasia, we used an enzyme-linked immunosorbent assay to measure serial changes of the serum M-CSF level during 25 intensification chemotherapy courses given to seven patients with acute non-lymphocytic leukemia who were in complete remission. Three M-CSF peaks were observed during therapy: the first peak was during or just after chemotherapy, the second peak was around the leukocyte nadir, and the third peak coincided with a rapid increase in the monocyte count. We could find no significant correlation between the height of the second peak and the time from the initiation of therapy to hematological recovery. On the other hand, there was a significant positive correlation between the height of the second peak and the interval from the last day of chemotherapy to the peak (r = 0.62, p = 0.001), and there was a significant negative correlation between the peak height and the time from the peak until hematological recovery (defined as a neutrophil count of over 500/microliters (r = -0.63, p = 0.001) and a leukocyte count of over 1,000/microliters (r = 0.55, p = 0.008)). However, we found only a weak correlation between the peak height and monocyte recovery. These data suggest that increased M-CSF levels lead to the stimulation of granulocyte progenitors, and that we can predict the time of neutrophil recovery by monitoring the serum M-CSF level and finding its peak.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Daunorubicin; Enzyme-Linked Immunosorbent Assay; Etoposide; Female; Humans; Leukemia, Myeloid, Acute; Leukocyte Count; Leukopenia; Macrophage Colony-Stimulating Factor; Male; Mercaptopurine; Middle Aged; Mitoxantrone; Predictive Value of Tests; Prednisone; Remission Induction; Vindesine

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Daunorubicin; Drug Administration Schedule; Female; Humans; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Prednisolone; Remission Induction; Survival Rate

A patient with myelocytic leukemia who showed electrical alternans of the T-U wave with no change in the QRS complex following chemotherapy is described. Electrocardiogram taken 4 days later showed ventricular quadrigeminy in which the T-U wave of the first sinus beat after the ventricular premature contraction was markedly less prominent compared to the successive two sinus beats which showed marked prolongation and inverted T-U waves. The causative factors for alternans of T-U waves may include hypochloremic alkalosis with hypopotassemia and myocardial damage by anticancer drugs such as daunomycin and aclarubicin chloride used for the underlying disease.

Topics: Aclarubicin; Antineoplastic Combined Chemotherapy Protocols; Arrhythmias, Cardiac; Cytarabine; Daunorubicin; Electrocardiography; Humans; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Middle Aged

From 1984 to 1989, we treated 34 adult patients with acute myelogenous leukemia (AML) with cytarabine, daunorubicin and 6-mercaptopurine for remission induction chemotherapy. One or two courses of consolidation chemotherapy with the same regimen as induction chemotherapy were given subsequently. No maintenance chemotherapy or central nervous system prophylaxis was administered. These patients included 23 men and 11 women, and had a mean age of 39. Eight of them older than 60 years of age were defined as elder age group. The overall complete remission (CR) rate was 62% (21/34), with elder versus younger age group 12.5% (1/8) vs. 77% (10/26). In patients who got CR after chemotherapy (3 cases with bone marrow transplantation and 1 case with only one course of chemotherapy were excluded), the median remission duration was 8 months, the median survival was 11.4 months, and the 2-year survival rate was 13.8%. Five cases died of complication of chemotherapy (2 septic shock and 3 intracerebral hemorrhage), and four of them were older than 60 years of age. In conclusion, this combined chemotherapy was as effective as that reported in western literature in treating AML in terms of CR rate. However, the 2-year survival rate was lower. The toxicity was acceptable, but the dosages of daunorubicin should be reduced in patients older than 60 years of age. Accordingly, to obtain a better prognosis in treating AML, further therapeutic modalities, such as bone marrow transplantation, methods with higher sensitivity in detecting residual leukemic cells, and new effective drugs, are mandatory.

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Daunorubicin; Drug Evaluation; Female; Humans; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Middle Aged; Remission Induction

To determine whether the pharmacokinetics of 6-mercaptopurine (6-MP) would show dose dependency, we studied three different single oral doses in eight children (aged 3.6 to 15.1 years) with acute leukemia in remission. Marked interindividual differences in maximum plasma concentration (Cmax) and the area under the plasma concentration-time curve (AUC) were observed when children received the 50 mg/m2 dose. This variability decreased when the doses were increased. Six of the eight children showed a disproportionate increase in the AUC with increasing doses; the other two had a proportionate relationship between the AUC and dose. Overall mean (+/- SD) Cmax and AUC values increased disproportionately (88 +/- 123, to 326 +/- 194, to 653 +/- 344 ng/ml for Cmax, and 147 +/- 180, to 451 +/- 177, to 1291 +/- 415 ng/ml per hour for AUC, respectively) when the dose increased from 50 to 87.5 mg/m2 and then to 175 mg/m2. The results suggest that a saturable first-pass metabolism of oral 6-MP occurs with increasing oral doses in some, but not all, children. Whether and to what extent this pharmacokinetic character of oral 6-MP affects the interindividual difference in systemic exposure to the drug in children with leukemia receiving maintenance therapy require further studies.

Topics: Administration, Oral; Adolescent; Child; Child, Preschool; Dose-Response Relationship, Drug; Female; Half-Life; Humans; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Remission Induction; Time Factors

A 25-year-old woman was diagnosed as acute myeloblastic leukemia (M1 in FAB classification) in May 1983, and treated with DCMP regimen, which led to the complete remission. Intensification therapies and maintenance therapy with OK-432 were continued until August 1988, and 10 months later she conceived. She delivered a healthy 2,680 g male baby at 36th week of pregnancy by Cesarean section because of abruptio placentae. This case suggests that normal pregnancy is possible in patients with acute leukemia who received anti-cancer drugs.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Daunorubicin; Female; Humans; Leukemia, Myeloid, Acute; Mercaptopurine; Prednisolone; Pregnancy; Remission Induction

Using clotting assay and radioimmunoassay (RIA), tissue factor activity (TFA) and TF related antigen (TFR:AG) were determined in an extracellular culture medium of HL-60 cells. After 12 h incubation, TFA and TFR:AG in the medium with endotoxin (EDX: 1 microgram/ml) reached maximums which were 1.8 and 2.1 times greater than those in the medium without EDX, respectively. In the leukemic cells of 10 patients with acute nonlymphoid leukemia (ANLL), TFR:AG showed a significant correlation with TFA (p less than 0.01). On day 1 of the induction chemotherapy, TFR:AG in the 7 patients with DIC significantly increased to 288.9 +/- 153.1 ng/ml (p less than 0.01), whereas no increase in TFR:AG was recognized in the 3 patients without DIC. These results suggest that TF may be released from leukemic cells into the culture medium or blood stream, and that this may correlate with the development of DIC.

Topics: Antineoplastic Combined Chemotherapy Protocols; Blood Coagulation; Cytarabine; Daunorubicin; Disseminated Intravascular Coagulation; Endotoxins; Humans; Leukemia, Myeloid, Acute; Mercaptopurine; Prednisolone; Thromboplastin; Tumor Cells, Cultured

Topics: Adenocarcinoma; Adult; Antineoplastic Combined Chemotherapy Protocols; Cytosine; Daunorubicin; Humans; Ileal Neoplasms; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Thioguanine

The objective of the current study is to clarify the concept and to demonstrate the encouraging results of individualized chemotherapy for adult acute nonlymphocytic leukemia. Settlement of target point for remission induction and individual adjustment of the treatment schedules according to response to therapy is fundamental for the treatment strategy. Since 1982, 37 consecutive adults with newly diagnosed acute nonlymphocytic leukemia were treated with individualized chemotherapy using intensive DCMP sequential multi-step therapy. Eighty-four percent of patients entered CR. Actuarial remission duration at greater than 4 years was 63.4 +/- 10.2% (95% confidence interval).

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Daunorubicin; Drug Administration Schedule; Drug Evaluation; Female; Humans; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Middle Aged; Prednisolone; Remission Induction

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Child; Cyclophosphamide; Humans; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Neoplasm Recurrence, Local; Pneumonia, Viral; Prednisone; Remission Induction; Time Factors

Acute myeloblastic leukemia (AML) was diagnosed in a 54-year-old male who had been known to carry a chronic hepatitis B surface antigen (HBsAg) from June, 1983. Prompt remission was achieved with combination chemotherapy of BHAC-DMP. Follow-up maintenance and an intensification of this chemotherapy had been given for five years. He was readmitted to our hospital in March, 1988 because a mass was detected in the right lobe of the liver by ultrasonography. His serum alpha fetoprotein (AFP) level was found to be 180.1 ng/ml, and was diagnosed as having a hepatocellular carcinoma though there was no evidence of liver cirrhosis. A curative right hepatectomy was performed in May, 1988 after transcatheter arterial embolization and portal embolization. After resection of the tumor, the AFP level decreased to 10.7 ng/ml and no HbsAg was detected in the serum.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Hepatocellular; Combined Modality Therapy; Cytarabine; Daunorubicin; Embolization, Therapeutic; Hepatectomy; Hepatitis B Surface Antigens; Humans; Leukemia, Myeloid, Acute; Liver Neoplasms; Male; Mercaptopurine; Middle Aged; Neoplasms, Multiple Primary; Prednisolone; Remission Induction

One hundred ninety six previously untreated patients of adult acute nonlymphocytic leukemia (ANLL) were treated with B-DOMP therapy. 102 patients were treated in the conventional rooms and 94 patients were in the laminar airflow rooms. The complete remission (CR) rates were 78.4%, and 84.0% respectively. The CR rate of the groups whose age was 60 years or older was higher for the patients treated in the laminar airflow room than those is conventional rooms (75.8% versus 60.0%), and the fatality from fungal infection was substantially lower for the laminar air-flow room patients. Non cross resistant chemotherapy based on alternate administration of Daunorubicin (DNR) and Aclarubicin (ACR) was given to 54 patients with ANLL in remission. The median duration of remission was 48.0 months, with 38.4%, patients in remission at 8 years. A plateau phase indicating freedom from the risk of leukemic recurrence is not clearly apparent yet. The most serious toxicity was drug induced cardiotoxicity from increased total dose by long term maintenance therapy. Newly planned post remission chemotherapy that incorporated Etoposide and Mitoxantrone with ACR and DNR was given to 35 patients with ANLL in remission. Seventy nine percent (79%) of patients were remaining in remission at 2 years. Because many patients experienced significant side effects after each course of therapy, intensive post remission chemotherapy should be used in a setting where the physician is always attending and ready to serve the patients.

Topics: Aclarubicin; Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Child; Cytarabine; Daunorubicin; Drug Evaluation; Etoposide; Female; Humans; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Middle Aged; Mitoxantrone; Prednisolone; Remission Induction; Survival Rate; Vincristine

Based on bone marrow findings and bone marrow stem cell kinetics and response to treatment, we have developed individualization of intensive induction and postremission chemotherapy for adult acute nonlymphocytic leukemia (ANLL). Thirty-four consecutive adults with ANLL were treated with an intensified induction regimen and a high dose sequential postremission therapy consisting of daunomycin, Ara-C, 6-MP and prednisolone (DCMP). The first course of remission induction was continued till achievement of a complete marrow aplasia which resulted in a decrease of leukocyte count less than 0.6-0.8 X 10(9)/L, a decrease of marrow nucleated cell count to less than 8 X 10(9)/L, and a decrease of marrow leukemic cell to less than 5%. Postremission therapy consisted of 4 courses of DCMP and a course of high-dose Ara-C. The first postremission course was initiated within 2-3 weeks subsequent to the last induction course. Twenty-eight of 34 patients (82.4%) achieved complete remission. The 4 year disease free survival rate was 64.4 +/- 14.0%. The results convinced us that individualized intensive induction and postremission therapy of adult ANLL given at the time of minimal residual leukemic disease in early remission might be sufficiently effective to produce long-term DFS to be considered potential cured.

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Cytarabine; Daunorubicin; Drug Evaluation; Female; Humans; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Middle Aged; Prednisolone; Remission Induction

We designed a short term intensive chemotherapy (DCMP-85 regimen) that completed 4 courses of postremission therapy without maintenance therapy in an effort to improve remission durations for adult patients with AML. Twenty six patients aged 14-65 yr were entered into this study. The rate of complete remission is 76.9%. A Kaplan-Meier analysis of patients entering remission predicts that 56% of patients will remain in remission at 3 years (median follow-up is 12 mo). Comparison three different conventional chemotherapies (DC(M)P, DCMP Two Step and BH-AC DMP), DCMP-85 has achieved higher CR rate and 3-year leukemia-free survival rate, so far. Therefore, we conclude short term intensive chemotherapy is getting better results.

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Daunorubicin; Drug Administration Schedule; Female; Humans; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Middle Aged; Prednisolone; Remission Induction; Survival Rate

Acute myelogenous leukemia (ALM) can be cured by chemotherapy. We have treated 121 adult AML cases for the past 9 years. With BHAC-DMP therapy starting in 1979, CR was obtained in 82% of 51 consecutive AML and the predicted 8-year continuing CR (CCR). Survival of CR cases was, 15 and 21%, respectively. Multivariate analysis of the prognostic factors revealed that % of blasts in the bone marrow at 2 weeks after the start of induction therapy was the most significant factor for CCR. Thus, we started BHAC-DMP (II) therapy with highly intensive induction therapy in 1983, but were forced to cancel this because of an intolerably high incidence of severe infections during the induction therapy. The CR rate was 76% in 29 consecutive patients, and the predicted 5-year CCR and survival of CR cases are 27 and 47%, respectively. Then we started M-85 protocol with intermediately intensive induction followed by 3 courses of highly intensive consolidation therapy using non-cross resistant drugs in 1985. The CR rate was 71% in 41 consecutive patients. Although 4 patients died of infections or myocardial infarction during the consolidation therapies, the predicted 2.5-year CCR and survival of CR cases are 76 and 74%, respectively, with a median follow-up of 28 months.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Cytarabine; Daunorubicin; Drug Evaluation; Follow-Up Studies; Humans; Leukemia, Myeloid, Acute; Leukocyte Count; Leukopenia; Mercaptopurine; Prednisolone; Prognosis; Remission Induction

38 consecutive, previously untreated adult patients with acute non-lymphocytic leukaemia (ANLL) were treated with BHAC-AMP (N4-behenoyl-1-beta-D-arabinofuranosyl-cytosine, aclacinomycin A, 6-mercaptopurine, and prednisolone) therapy between March 1980 and February 1985. 25 patients (65.8%) achieved complete remission (CR). Median CR duration and median survival of patients who achieved CR were 14, and 24 months, respectively. The Kaplan-Meier analysis revealed a probability for remaining in CR of 18.0% at 5 years. Analysis of failure cases revealed that most of them were due to resistant disease. Major toxicities were infection, diarrhoea, liver dysfunction, nausea and vomiting but these were acceptable. The results indicate that BHAC-AMP therapy is comparable to the regimen with daunorubicin and cytosine arabinoside and a further clinical trial is necessary for previously untreated adult patients with ANNL.

Topics: Aclarubicin; Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Female; Humans; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Middle Aged; Prednisolone

Twenty seven previously untreated patients of acute nonlymphocytic leukemia with age ranging from 30 to 77 years, received a 7-day remission induction regimen consisting of daunorubicin, cytosine arabinoside, 6-mercaptopurine and prednisolone (continuous-DCMP). Patients who achieved complete remission were given ten courses of consolidation therapy and followed without any maintenance therapy. The complete remissions were obtained in 7 of 15 patients (46.6%) 60 years and older, and in 11 of 12 patients (91.7%) 30-59, years of age. Although a high mortality during periods of marrow hypoplasia after the intensive induction therapy, and early relapses in the 60 years and older patients remain major problems, our data suggest the elderly patients deserve a trial of intensive combination chemotherapy.

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

Neutropenic enterocolitis, also known as typhlitis or ileocecal syndrome, in leukemic patients undergoing chemotherapy has a high reported mortality. A recent increase in the incidence of neutropenic enterocolitis is associated with aggressive chemotherapy for acute leukemia. In this report, we report the incidence, diagnosis, and treatment of neutropenic enterocolitis during low-dose DCMP and high-dose DCMP regimen for 95 adults with acute nonlymphocytic leukemia, and review the literature pertaining appropriate medical and surgical management, and method of prevention. Finally we propose the favorable results of gut sterilization for the treatment and prevention of the disease.

Topics: Adult; Agranulocytosis; Antineoplastic Combined Chemotherapy Protocols; Cohort Studies; Cytarabine; Daunorubicin; Enterocolitis, Pseudomembranous; Female; Humans; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Middle Aged; Neutropenia; Prednisolone

Topics: Aclarubicin; Acute Disease; Antineoplastic Combined Chemotherapy Protocols; Child; Cytarabine; Humans; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Naphthacenes; Pancreatitis; Vincristine

Sixteen children with refractory hematological malignancies were treated with a combination of BH.AC, aclacinomycin-A, 6-MP and predonisolone (BH-AC.AMP protocol). They were ALL(6), ANLL(8), CML(1) and NHL(1). The CR ratio was 17% in ALL, 50% in ANLL, and blast crisis of CML was treated successfully but NHL failed in the induction remission. Major complications were vomiting, nausea, gastrointestinal bleeding, hematuria and hemorrhagic cystitis. More than 10 days or 120 mg/m2 administration of aclacinomycin-A was thought to induce more severe side effects.

Topics: Aclarubicin; Adolescent; Antineoplastic Combined Chemotherapy Protocols; Child; Child, Preschool; Cytarabine; Drug Administration Schedule; Female; Humans; Infant; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Acute; Lymphoma; Male; Mercaptopurine; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prednisolone; Remission Induction

The sensitivity to cytosine arabinoside (Ara-C) of blast progenitors from 22 acute myeloblastic leukaemia (AML) patients was studied in methylcellulose and suspension cultures. Primary colony-formation (PE1) in methylcellulose reflects the terminal divisions of blast progenitors, while secondary colony formation (PE2) in methylcellulose and the clonogenic cells recovery in suspension are considered to be based on the self-renewal of blast progenitors. In any patient, PE2 or clonogenic cells in suspension were more sensitive to Ara-C than PE1. The results indicate that Ara-C effectively suppresses not only terminal divisions but also self-renewal of blast progenitors D10 Ara-C value, the dose required to reduce survival to 10% of control, for PE1, PE2 and clonogenic cells in suspension showed marked patient-to-patient variation. No significant correlation was found between D10 Ara-C in methylcellulose or suspension culture and the response to treatment with a combination chemotherapy of 6-mercaptopurine, Ara-C and daunorubicin. However, a relapsed patient whose D10 values in methylcellulose and suspension cultures were very high showed poor response to a high-dose Ara-C protocol, where Ara-C was given alone at a high dose. The application of chemosensitivity test as a prediction of the clinical outcome may be dependent on the treatment protocol.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Colony-Forming Units Assay; Cytarabine; Daunorubicin; Hematopoietic Stem Cells; Humans; Leukemia, Myeloid, Acute; Mercaptopurine; Middle Aged

Topics: Administration, Oral; Aged; Anemia, Refractory, with Excess of Blasts; Antineoplastic Combined Chemotherapy Protocols; Blast Crisis; Cytarabine; Daunorubicin; Drug Therapy, Combination; Female; Humans; Leukemia, Myeloid, Acute; Mercaptopurine; Prednisolone; Vitamin A; Vitamin D

Topics: Acute Disease; Adult; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Cytarabine; Daunorubicin; Female; Graft vs Host Disease; Humans; Leukemia, Myeloid, Acute; Mercaptopurine; Platelet Transfusion; Prednisolone; Transfusion Reaction

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Cytarabine; Daunorubicin; Drug Resistance; Female; Humans; Leukemia, Myeloid, Acute; Mercaptopurine; Remission Induction; Tumor Cells, Cultured; Uterine Neoplasms

Topics: Adult; Aged; Anemia, Refractory, with Excess of Blasts; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Daunorubicin; Female; Humans; Leukemia, Myeloid, Acute; Leukemia, Myelomonocytic, Chronic; Male; Mercaptopurine; Middle Aged; Myelodysplastic Syndromes; Prednisolone; Remission Induction; Vincristine

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cell Division; Cytarabine; Daunorubicin; Humans; Leukemia, Myeloid, Acute; Mercaptopurine; Middle Aged; Neoplastic Stem Cells; Prednisolone; Prognosis; Remission Induction; Tumor Stem Cell Assay

Topics: Aclarubicin; Adolescent; Adult; Age Factors; Aged; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Daunorubicin; Drug Resistance; Female; Humans; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Middle Aged; Prednisolone; Prognosis; Remission Induction; Vincristine

Chlorambucil is useful in patients with rheumatoid arthritis (RA) refractory to other agents but there is concern about the risk of haematological malignancy with this agent. A retrospective survey was performed to assess the incidence of all types of malignancy in 39 patients treated with chlorambucil (mean daily dose 4.25 mg, mean duration of treatment 25 months). These patients were compared with 30 patients with RA who received contemporaneously, the purine analogues azathioprine or 6-mercaptopurine (mean dose 100 mg, mean duration of treatment 24 months). Eight patients treated with chlorambucil and one patient receiving purine analogues developed cutaneous malignancy (p = 0.03). In the chlorambucil-treated patients these were mostly multiple and recurrent. Three patients treated with chlorambucil developed myeloid leukaemia or a preleukaemic state, whilst no patient treated with purine analogues developed this complication. The use of chlorambucil in RA is associated with an increased risk of cutaneous as well as haematological oncogenesis.

Topics: Acute Disease; Arthritis, Rheumatoid; Azathioprine; Carcinogens; Chlorambucil; Humans; Leukemia, Myeloid, Acute; Mercaptopurine; Pancytopenia; Time Factors

The effect of maintenance chemotherapy on remission duration was analyzed in 39 of 70 patients (56%) with acute promyelocytic leukemia (APL) who achieved complete remission on induction chemotherapy. Overall, the median remission duration was 26 months, with a 3-year remission rate of 42%. The 3-year remission rate was significantly higher in patients who received 6-mercaptopurine and methotrexate (POMP) during maintenance, compared with those who did not (56% versus 30%; P less than 0.01), and in patients who received long-term maintenance therapy (P less than 0.01). A multivariate regression analysis selected maintenance therapy with POMP to be the only statistically significant factor associated with long-term remission duration. The type of maintenance chemotherapy is important in overall prognosis of patients with APL, and should be investigated further.

Topics: Antineoplastic Combined Chemotherapy Protocols; Female; Humans; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Methotrexate; Middle Aged; Prednisone; Prognosis; Statistics as Topic; Time Factors; Vincristine

A sensitive and rapid assay for the quantitation of thioinosine monophosphate and thioguanosine monophosphate, the major intracellular active metabolites of mercaptopurine and thioguanine, respectively, has been developed. Neoplastic cells are extracted with trichloracetic acid, and the neutralized acid extracts are analyzed by ion-pairing high-performance liquid chromatography with dual-channel uv-wavelength detection. This technique provides a lower limit of sensitivity of 30 pmol of thioinosine monophosphate and 10 pmol of thioguanosine monophosphate. The number of cells assayed per sample was 2 X 10(7). This assay makes it possible to detect and quantitate low levels of thioinosine monophosphate and thioguanosine monophosphate present in neoplastic cells obtained directly from patients receiving mercaptopurine or thioguanine chemotherapy.

Topics: Bone Marrow; Cell Line; Chromatography, High Pressure Liquid; Guanine Nucleotides; Humans; Inosine Monophosphate; Inosine Nucleotides; Leukemia, Myeloid, Acute; Lymphoma; Mercaptopurine; Thioguanine; Thionucleotides

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Arabinofuranosylcytosine Triphosphate; Cytarabine; Daunorubicin; Dose-Response Relationship, Drug; Humans; Infusions, Intravenous; Leukemia, Myeloid, Acute; Mercaptopurine; Methotrexate; Prednisone; Time Factors; Translocation, Genetic; Vincristine

Three cases of secondary leukemia developing after chemotherapy and/or radiotherapy for myeloma, mycosis fungoides, and non-Hodgkin's lymphoma are reported. The first case was a 51-year-old man with IgG-lambda myeloma, treated with melphalan and prednisolone, who developed acute myelomonocytic leukemia 54 months after the diagnosis of myeloma. The second case was a 54-year-old woman with mycosis fungoides treated with radiation, predonine, and cyclophosphamide, who developed acute megakaryoblastic leukemia 298 months after the diagnosis of mycosis fungoides. The third case was a 35-year-old woman with stage IV non-Hodgkin's lymphoma treated with VEMP who developed acute myelogenous leukemia 26 months after the diagnosis of malignant lymphoma. All cases showed pancytopenia and two of three cases had morphologic abnormality in several hemopoietic cell lineages in the leukemic stage. There is a possibility that second malignancies are an increasingly recognized complication in the patients treated with a large amount of chemo-radiotherapy.

Topics: Adult; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Female; Humans; Leukemia; Leukemia, Megakaryoblastic, Acute; Leukemia, Myeloid, Acute; Leukemia, Radiation-Induced; Lymphoma, Non-Hodgkin; Male; Melphalan; Mercaptopurine; Middle Aged; Multiple Myeloma; Mycosis Fungoides; Pancytopenia; Prednisolone; Vincristine

Topics: Antineoplastic Combined Chemotherapy Protocols; Chemical and Drug Induced Liver Injury; Humans; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Middle Aged; Time Factors

2 patients with acute megakaryoblastic leukaemia (AMKBL) were successfully treated with a combination of aclarubicin hydrochloride (an anthracycline), enocitabine (a derivative of cytosine arabinoside) and 6-mercaptopurine (6-MP) or 6-thioguanine (6-TG). They achieved a complete remission following 1 or 2 courses. They remained well and in complete remission throughout 3 courses of consolidation therapy, a total of 9 weeks. The results of remission induction therapy of AMKBL have been reviewed in the literature. 4 of 7 adult patients, including our cases, treated with 3 drugs, anthracycline, cytosine arabinoside or its derivative and 6-TG or 6-MP, achieved a complete remission. AMKBL may not have so poor a prognosis as previously believed.

Topics: Aclarubicin; Adolescent; Adult; Aged; Antibiotics, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Blood Transfusion; Cytarabine; Female; Humans; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Middle Aged; Naphthacenes; Thioguanine

Sixty patients with acute promyelocytic leukemia were treated between 1973 and 1984. The overall median survival was 16 months with a five-year survival rate of 31 percent. The complete remission rate was 53 percent and was similar whether they received amsacrine- or anthracycline-based regimens (60 percent versus 51 percent). The median remission duration was 29 months. At five years, 43 percent of patients with responses to treatment had continuous remission and 57 percent were alive. Salvage therapy produced remissions in 53 percent of patients during first relapse, with two long-term survivors after further consolidation with bone marrow transplantation. Early fatal hemorrhage associated with disseminated intravascular coagulopathy during induction therapy occurred in 16 patients (26 percent). Multivariate analysis of the pretreatment patient characteristics significantly associated with an increased risk of fatal hemorrhage identified four that have primary prognostic importance: thrombocytopenia, elevated absolute blast and promyelocyte counts, old age, and anemia. Patients having up to two unfavorable features had a low risk of fatal hemorrhage compared with those who had more than two (5 percent versus 58 percent; p less than 0.0001). Overall, patients who received heparin had a lower incidence of fatal hemorrhage than those who did not (19 percent versus 32 percent). Heparin therapy was not beneficial to those at low risk but was associated with a trend towards decreased hemorrhagic deaths among high-risk patients (45 percent versus 67 percent). Cytogenetic studies demonstrated the characteristic 15;17 translocation in 73 percent of patients with analyzable metaphases, whereas 12 percent had other karyotypic abnormalities. Remission induction was often associated with a gradual atypical morphologic evolution into remission without intermediate hypoplasia with the interim marrows showing a high proportion of blasts. It is concluded that acute promyelocytic leukemia is a unique disease with a high potential for cure. Knowledge of its prognosis using present frontline and salvage therapy, of the factors related to fatal hemorrhage, and of the unusual patient marrow profiles during remission induction may improve the therapeutic approach.

Topics: Aminoacridines; Amsacrine; Antineoplastic Combined Chemotherapy Protocols; Blood Transfusion; Cytarabine; Daunorubicin; Disseminated Intravascular Coagulation; Doxorubicin; Female; Hemorrhage; Hospitals, Teaching; Hospitals, University; Humans; Karyotyping; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Methotrexate; Middle Aged; Prednisone; Prognosis; Risk; Texas; Time Factors; Vincristine

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

Thioguanine and mercaptopurine are clinically important agents in widespread use for the treatment of acute leukemia. In this study the effect of low, physiological concentrations of hypoxanthine on thiopurine cytotoxicity was examined in the HL-60 human acute promyelocytic leukemia cell line. Initially the effect of cell concentration on medium hypoxanthine levels was investigated. When 10(5) to 10(6) cells/ml were used, medium hypoxanthine concentrations fell to undetectable (less than 0.1 microM) levels by 24 h, due to cell utilization. However, when the cell density was reduced to 10(3) cells/ml, it was possible to maintain a medium hypoxanthine level as low as 0.5 microM for 24 h without significant hypoxanthine depletion. This allowed for the investigation of the extent to which physiological concentrations of hypoxanthine (1.0 to 10 microM) could modulate thiopurine cytotoxicity. HL-60 cells were incubated in medium containing from 1.0 to 100 microM hypoxanthine concentrations and varying levels of thioguanine or mercaptopurine for 24 h. Cells were then washed and cloned in soft agar. Physiological concentrations of hypoxanthine (1.0 to 10 microM) provided significant protection to HL-60 cells from the cytotoxic effects of both thioguanine and mercaptopurine. An increase in medium hypoxanthine level from 1.0 to 3.0 microM resulted in a 3-fold increase in the thiopurine concentration required to kill 50% of cells. There was a linear relationship between the thiopurine concentration required to reduce clonogenic survival by 50% and medium hypoxanthine level over the hypoxanthine concentrations studied. Although thioguanine was 200-fold more potent than mercaptopurine, and an analogue of guanine rather than hypoxanthine, there was a similar degree of modulation of the cytotoxicity of both agents by hypoxanthine. These results indicate that low, physiological hypoxanthine concentrations can significantly modulate thiopurine cytotoxicity and suggest that endogenous hypoxanthine pools may have an important effect on the clinical activity of thioguanine and mercaptopurine.

Topics: Cell Count; Cell Line; Cell Survival; Dose-Response Relationship, Drug; Humans; Hypoxanthine; Hypoxanthines; Leukemia, Myeloid, Acute; Mercaptopurine; Thioguanine

Fifty-one consecutive previously untreated adult patients with acute myelogenous leukemia (AML) were treated with BHAC-DMP (N4-behenoyl-I-beta-D-arabinofuranosyl-cytosine, daunorubicin, 6-mercaptopurine, and prednisolone) therapy. Forty-two patients (82.4%) achieved complete remission (CR). The Kaplan-Meier analysis revealed a probability for remaining in remission of 14% and for survival of 23% at 6 years. Pretreatment factors related to the achievement of CR, such as age, French-American-British (FAB) classification and WBC at the start of treatment, were not identified. Factors related to the CR duration and survival time of the patients who had achieved CR were first analyzed by a univariate analysis with the generalized Wilcoxon test. WBC count at the start of treatment, percent of blasts in the marrow at 1 and 2 weeks after the initiation of therapy, days required until CR, number of courses of induction therapy required until CR, and days required for the disappearance of circulating blasts were identified as statistically significant prognostic factors. When these characteristics were further analyzed by the Cox multivariate regression model, the percent of blasts in the bone marrow at 2 weeks was the most important prognostic factor with a statistical significance, and WBC count at the start of treatment and days required until CR (or number of courses required to achieve CR) were also important factors, with borderline significance.

Topics: Acute Disease; Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Daunorubicin; Female; Humans; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Middle Aged; Prednisone; Prognosis; Statistics as Topic

Topics: Adult; Amphotericin B; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Daunorubicin; Humans; Leukemia, Myeloid, Acute; Liver Abscess; Male; Mercaptopurine; Portal System; Prednisolone

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Busulfan; Carmustine; Combined Modality Therapy; Cyclophosphamide; Cytarabine; Doxorubicin; Drug Combinations; Drug Evaluation; Female; Humans; Leukemia, Myeloid, Acute; Male; Meningeal Neoplasms; Mercaptopurine; Methotrexate; Middle Aged; Mitoguazone; Prednisone; Thioguanine; Vincristine

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Child; Child, Preschool; Cytarabine; Doxorubicin; Female; Humans; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Prednisolone

Topics: Aclarubicin; Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Child; Child, Preschool; Cytarabine; Female; Humans; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Middle Aged; Naphthacenes; Prednisolone

Numerous agents induce differentiation and maturation of neoplastic and dysplastic myeloid cells in vitro and some of these agents have been used with limited success in the treatment of patients with myelodysplastic syndromes (MDS) and myeloid leukaemias. We recently proposed that physiological and pharmacological agents which enhance differentiation and maturation in vitro act by two fundamentally different routes: (1) by hastening the progression through various differentiation/maturation steps; (2) by slowing proliferation (usually by inhibition of DNA synthesis). In order to test this thesis we looked for synergistic effects on differentiation using pairs of agents from the two groups in cultures of cells from myelodysplastic and acute myeloid leukaemia (AML) patients and from normal marrow donors. The results with three MDS, two AML and three normal samples show that combinations of differentiation inducing agents (retinoic acid, N-methylformamide) with DNA synthesis inhibitors (6-mercaptopurine, cytosine arabinoside and aphidicolin) produce a differentiation inducing effect equivalent to that of 10-100, or even 1000 fold higher concentrations of single agents. Myelotoxic effects in vitro were not synergistic. The use of these synergistic combinations should greatly enhance the usefulness of differentiation inducers in the therapy of MDS and myeloid leukaemia.

Topics: Antineoplastic Combined Chemotherapy Protocols; Aphidicolin; Bone Marrow; Bone Marrow Diseases; Cell Differentiation; Cells, Cultured; Cytarabine; Diterpenes; DNA; Drug Synergism; Formamides; Humans; Leukemia, Myeloid, Acute; Mercaptopurine; Preleukemia; Syndrome; Tretinoin

We present a case of primary colonic plasmacytoma associated with acute myelogenous leukemia in a 32-year-old man. The neoplastic plasma cells revealed monoclonal lambda-light chains in the cytoplasm using immunoperoxidase techniques. Histochemical and electron microscopic findings are described with a review of the literature.

Topics: Adult; Colon; Colonic Neoplasms; Cytarabine; Daunorubicin; Humans; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Plasmacytoma; Prednisolone

Sixteen of 20 patients(80%) with adult ANLL treated with B H-AC X AMP therapy attained complete remission (CR). According to the FAB classification, CR rate was 6 out of 8 (75%) for M1, 3 out of 5 (60%) for M2, 2 out of 2 (100%) for M3, and 5 out of 5 (100%) for M4. The median of remission duration in 16 patients who attained CR was 8 months and appeared to be longer in patients with M2, rather than other types, of leukemia than in those with the other types of leukemia. BH-AC X AMP therapy is highly effective for remission induction in adult ANLL and long term disease free survival could be expected by addition of appropriate maintenance therapy.

Topics: Aclarubicin; Adolescent; Adult; Aged; Antibiotics, Antineoplastic; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Female; Humans; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Middle Aged; Naphthacenes; Prednisolone

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Daunorubicin; Deoxycytidine Monophosphate; Female; Humans; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Middle Aged; Prednisolone

Topics: Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Daunorubicin; Drug Administration Schedule; Humans; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Middle Aged; Prednisolone; Vincristine

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Chromosome Aberrations; Cytarabine; Daunorubicin; Female; Humans; Leukemia, Myeloid, Acute; Mercaptopurine; Prednisolone; Vincristine

A 28-year-old man developed AML 18 months after a diagnosis of non-Hodgkin's lymphoma, diffuse small cell type, clinical stage IIA. Induction therapy for the lymphoma consisted 60Co 4000 rads bilaterally to the cervical areas and 2000 rads to the right cervical area. Complete remission was attained. Nineteen courses of combination chemotherapy with Vincristine (VCR), 6-meraptopurine (6 MP), cyclophosphamide (CY) and predonisolone (pred) was added (Total dose: VCR; 26.5 mg, 6 MP; 3320 mg, CY; 3350 mg, pred; 4310 mg). Seven days after the final chemotherapeutic treatment he developed AML with DIC. Leukemic cells were peroxidase and specific esterase (naphthol AS-D chloroacetate) positive. Induction therapy for the AML consisting of DCMP (Daunomycin, Cytosine arabinosid, 6 MP and pred) and VCR (vindesine, CY and pred) was unsuccessful. The patient died of cranial hemorrhage 3 month after the diagnosis of acute leukemia. Autopsy revealed no recurrence of non-Hodgkin's lymphoma in the lymph nodes, bone marrow, spleen and liver. Seven other cases reported in the Japanese literature are reviewed.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Disseminated Intravascular Coagulation; Drug Administration Schedule; Humans; Leukemia, Myeloid, Acute; Lymphoma; Male; Mercaptopurine; Prednisolone; Radiotherapy Dosage; Vincristine

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Daunorubicin; Female; Humans; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Middle Aged; Prednisolone

Topics: Antineoplastic Agents; DNA, Neoplasm; Female; Humans; Leukemia, Myeloid, Acute; Mercaptopurine; Middle Aged; Mycophenolic Acid

Eight adults with acute non-lymphocytic leukemia refractory to BH-AC.DMP therapy (N4-behenoyl-1-beta-D-arabinofuranosylcytosine, daunomycin, 6-mercaptopurine and prednisolone) were treated with a combination therapy of anthracycline antibiotics: adriamycin and aclacinomycin A (AA therapy). Four of five patients, who had received neither adriamycin nor aclacinomycin A previously, achieved complete remission after one course of AA therapy with a median time to remission of 24.5 days (ranging from 21 to 31 days). Two cases were in first remission induction phase and the other two were in first of third relapse. Three cases still maintain complete remission and the durations of remission range from 3 to over 14 months. Major side effects were loss of hair (100%) and myocardial damage (64%). T wave flattening and appearance of U wave in ECG were noted a few days after receiving chemotherapy but those changes returned to normal within 2 to 3 weeks. Ventricular fibrillation was observed in one case, which was refractory to chemotherapy and complicated by sepsis and electrolytes imbalance. Thus, this regimen deserves to be tried as a remission induction in patients with refractory acute non-lymphocytic leukemia.

Topics: Aclarubicin; Adolescent; Adult; Aged; Cytarabine; Daunorubicin; Doxorubicin; Drug Resistance; Drug Therapy, Combination; Female; Humans; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Middle Aged; Naphthacenes; Prednisolone

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; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Child; Cytarabine; Daunorubicin; Drug Therapy, Combination; Female; Humans; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Methotrexate; Middle Aged; Prednisolone; Vincristine

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Daunorubicin; Female; Humans; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Middle Aged; Prednisolone

Topics: Adult; Cytarabine; Daunorubicin; Drug Therapy, Combination; Female; Humans; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Middle Aged; Prednisone

Topics: Adolescent; Adult; Aged; Antineoplastic Agents; Cytarabine; Daunorubicin; Drug Therapy, Combination; Female; Humans; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Middle Aged; Prednisolone; Vincristine

Topics: Aclarubicin; Adult; Cytarabine; Drug Therapy, Combination; Female; Humans; Leukemia; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Middle Aged; Naphthacenes; Prednisolone

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

Topics: Bone Marrow; Cells, Cultured; Clone Cells; Diagnosis, Differential; Etoposide; Humans; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Mercaptopurine; Muramidase; Prognosis; Transcobalamins

An unexpectedly high rate of long-term survivors in acute myeloid leukemia (AML) has been observed in a group of patients who achieved a first complete remission (CR) after induction of a therapeutic regimen including daunorubidomycine, vincristine, prednisone and stanozolol, and anabolizing steroid. The rate of CR was 52%. Maintenance therapy was very simple and the only association with stanozolol during this period suggested to us that an androgen, at low dosages, might be responsible for the unusual long-term survival time (45 months with a 95% confidence limit from 30 to 86 months). On the basis of our first observation, high dosages of the androgen were used during the induction phase of treatment but failed to demonstrate any advantage when associated with a drug regimen, including cytosine arabinoside (ARA-C). The reevaluation of each parameter for our group of patients did not allow selection of patients in terms of their age or the hematologic data obtained at presentation. Effects of androgen on the socalled normal hemopoietic cells and on the leukemic cells are discussed, particularly the possible antagonistic effect with ARA-C. A prospective statement is made concerning the possible condition of the prolongation of the complete remission in AML according to some experimental data which enforce the stimulative activity of androgen on the myeloid proliferation.

Topics: Adolescent; Adult; Antineoplastic Agents; Chemical and Drug Induced Liver Injury; Child; Child, Preschool; Cytarabine; Daunorubicin; Drug Therapy, Combination; Female; Humans; Hydroxyurea; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Middle Aged; Prednisone; Stanozolol; Vincristine; Virilism

We designed a protocol to address the problem of relapse from complete remission in acute myelogenous leukemia. Patients in remission were treated for 14 months; early and later intensification of chemotherapy, sequential drug combinations, and high-dose continuous infusions of cytarabine were included. Eighty-three consecutive patients under 50 years of age were entered into this study from February 1976 to October 1979. The rate of complete remission is 70 per cent. A Kaplan-Meier analysis predicts that 49 +/- 17 per cent of patients (mean +/- 2 S.D.) who entered complete remission will remain free of disease at two years. Durations of complete remission for patients in the 0 to 17-year and 18 to 50-year age groups are comparable.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Blood Transfusion; Child; Child, Preschool; Cytarabine; Doxorubicin; Drug Administration Schedule; Drug Therapy, Combination; Female; Granulocytes; Humans; Infant; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Methotrexate; Methylprednisolone; Middle Aged; 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

Topics: Adolescent; Adult; Aged; Antineoplastic Agents; Cyclophosphamide; Cytarabine; Daunorubicin; Drug Administration Schedule; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Hydroxyurea; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Middle Aged; Prednisone; 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: 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

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

Topics: Adolescent; Antineoplastic Agents; Child; Child, Preschool; Cyclophosphamide; Cytarabine; Drug Therapy, Combination; Female; Humans; Infant; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Prednisolone; Vincristine

The degree to which anticancer drugs suppressed incorporation of tritiated thymidine into leukaemic cells was measured in 26 patients with acute leukaemia. Subsequent achievement of remission correlated best with suppression by cytosine arabinoside (ara-C). 6 of 7 patients with acute myelocytic and myelomonocytic leukaemia whose cells demonstrated suppression by ara-C of 3H-thymidine incorporation of 15% or less of control counts subsequently achieved remission, while 4 of 6 patients whose cells showed smaller degrees of inhibition did not achieve remission. Patients with acute lymphocytic leukaemia showed a similar pattern.

Topics: Adult; Aged; Cells, Cultured; Cyclophosphamide; Cytarabine; Depression, Chemical; Drug Therapy, Combination; Female; Humans; In Vitro Techniques; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Methotrexate; Middle Aged; Prednisone; Prognosis; Remission, Spontaneous; Thymidine; Tritium; 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: Adult; Antineoplastic Agents; Cyclophosphamide; Cytarabine; Daunorubicin; Drug Therapy, Combination; Humans; Leukemia, Myeloid, Acute; Mercaptopurine; Methotrexate; Prednisone; Prognosis; Remission, Spontaneous; Vincristine

A new non-radioisotopic technique is described for measuring rates of intracellular formation by human leukemic blasts of 6-thioguanine nucleotide metabolites, obligatory intermediates in the antineoplastic action of both 6-mercaptopurine and 6-thioguanine itself. The method is both specific and sensitive, and involves combined high-performance liquid chromatography and flow fluormetric detection of oxidized 6-thioquanine nucleotides in alkaline permanganate-treated cell extracts. Non-metabolized 6-thioguanine and 6-thioxanthine are also separated and quantitated in this system, permitting complementary in vivo pharmacokinetic analysis. The assay may be applied to detect resistant disease at an early stage in therapy, and thereby provides the opportunity for alternative treatments to be instituted.

Topics: Body Fluids; Chromatography, High Pressure Liquid; Fluorometry; Humans; Intracellular Fluid; Leukemia, Myeloid, Acute; Mercaptopurine; Thioguanine; Thionucleotides

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

Topics: Adult; Cyclophosphamide; Cytarabine; Daunorubicin; Drug Therapy, Combination; Humans; Leukemia, Myeloid, Acute; Mercaptopurine; Methotrexate; Prednisone; Thioguanine; Vincristine

For the purpose of preventing a relapse of acute leukemia which is currently the major problem in the successful treatment of the disease, repeated consolidation or intensification therapy during the first year following remission is important. To evaluate these therapies, we investigated the serial changes in CFU-C's of the marrow cells from 12 patients with acute nonlymphocytic leukemia in remission and tried to estimate the relationship between the intensity of consolidation or intensification therapy and the duration of remission, utilizing the degree of reduction in CFU-C's seven days after these treatments as an indicator. As a result, after 21 out of 22 courses of therapy where CFU-C's were reduced significantly after the therapy, the patients were still in remission at the time of the next intensificiation therapy (at most for about 100 days). On the other hand, after five out of ten courses where CFU-C's were not reduced significantly, the patients were in relapse at the time of the next intensification therapy. From these results, it may be inferred that cases whose CFU-C's are not reduced significantly should be treated intensively again within a short period.

Topics: Acute Disease; Adult; Child; Colony-Forming Units Assay; Cytarabine; Daunorubicin; Drug Therapy, Combination; Female; Humans; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Middle Aged; Prednisolone; Remission, Spontaneous

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

Following a critical review of todays predominating opinion on the morphological definition of leukosis cells in severe paraleukoblastic leukosis three cases of the so-called aleukemic from of severe leukosis are described. Such rare cases, in which -- as it is known -- the peripheral blood remains normal while bone marrow shows a paraleukoblastic metaplasia seem to be good evidence for the myelogenic nature of the cells during severe paraleukoblastic leukosis.

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

The therapeutic regimens for acute myelogenous leukemia in 2 different periods of time will be described with comparison of their results. A. 28 adults were treated with cytosine arabinoside and 6-thioguanine only. Thereby, 28% complete and 16% partial remissions were achieved. The mean duration of the complete remissions was 23 weeks. The mean survival time of the patients with complete remission amounted to 53 weeks B. 46% complete and 12% partial remissions were obtained in 37 patients treated with cytosine arabinoside and 6-thioguanine doubling the dosage of the above mentioned regimen followed by 3 cycles of TRAP (and COAP). Using a maintenance therapy with modified TRAP, COAP, and POMP cycles the complete remissions lasted 47 weeks at an average. The mean survival time of patients with complete remission was 87 weeks after start of treatment.

Topics: Adult; Aged; Cyclophosphamide; Cytarabine; Daunorubicin; Drug Therapy, Combination; Female; Humans; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Methotrexate; Middle Aged; Prednisone; Remission, Spontaneous; Thioguanine; Time Factors; Vincristine

Cytogenetic studies of the bone marrow and peripheral blood with the quinacrine fluorescence banding technique in a patient with the clinical diagnosis of acute myeloblastic leukemia revealed the Philadelphia chromosome due to a translocation between chromosomes 22 and 9. He had been exposed to the atomic bomb in Hiroshima, and some hours after the exposure he wandered into the hypocenter.

Topics: Chromosome Aberrations; Chromosomes, Human, 21-22 and Y; Chromosomes, Human, 6-12 and X; Cytarabine; Humans; Japan; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Middle Aged; Nuclear Warfare; Prednisolone; Translocation, Genetic

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

Twenty-five patients with acute myeloid leukaemia were treated with three quadruple drug combinations in predetermined rotation: TRAP (thioguanine, daunorubicin, cytarabine, prednisolone); COAP (cyclophosphamide, vincristine, cytarabine, prednisolone); and POMP (prednisolone, vincristine, methotrexate, mercaptopurine). Fifteen patients (60%) achieved complete remission and five (20%) partial remission. For maintenance, five-day courses of drugs were administered every 14 to 21 days and doses were increased to tolerance. The median length of complete remission was 66 weeks. In eight patients remission maintenance treatment was discontinued and some remained in complete remission for over two years. In this series the remission induction rate was comparable with that reported for other regimens and complete remission lasted longer with this intensive maintenance regimen than with others. Nevertheless, the TRAP programme must still be regarded as only palliative treatment for acute myeloid leukaemia.

Topics: Adolescent; Adult; Aged; Antineoplastic Agents; Child; Child, Preschool; Cyclophosphamide; Cytarabine; Daunorubicin; Drug Therapy, Combination; Female; Humans; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Methotrexate; Middle Aged; Prednisolone; Remission, Spontaneous; Thioguanine; Vincristine

Topics: Antineoplastic Agents; Asparaginase; Child; Daunorubicin; Humans; Immunotherapy; Leukemia, Myeloid, Acute; Mercaptopurine; Methotrexate; Prednisone; Remission, Spontaneous; 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 PRPP concentrations, PRPP formation, and phosphorylation of 6-mercaptopurine in leukocyte suspensions and homogenates prepared from leukemic patients were studied...

Topics: Amidophosphoribosyltransferase; Animals; Humans; Hypoxanthine Phosphoribosyltransferase; Hypoxanthines; In Vitro Techniques; Inosine; Inosine Monophosphate; Leukemia; Leukemia L1210; Leukemia, Myeloid, Acute; Leukocytes; Mercaptopurine; Phosphoribosyl Pyrophosphate; Purine-Nucleoside Phosphorylase

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

A case report of a patient who developed acute myelogenous leukemia 15 years after injection of Thorotrast and who has been in a sustained long term remission for 14 years is presented with a review of the problems associated with Thorotrast, subsequently shown to be radioactive with long term sequelae.

Topics: Adolescent; Angiography; Female; Humans; Leukemia, Myeloid, Acute; Leukemia, Radiation-Induced; Lymph Nodes; Mercaptopurine; Remission, Spontaneous; Spleen; Thorium Dioxide

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

A regime of treatment of acute non-lymphoblastic leukemia in adult, employing DMCP protocol, especially two step method consisting of daunorubicin, cytosine arabinoside, 6-mercaptopurine and prednisolone is described. Out of 32 adult patients with ANLL treated with DCMP regime 26 (81.3%) achieved complete remission. The median durations of complete remission and survival were 53 weeks and 54 weeks, respectively. The longest duration of complete remission was more than 220 weeks, and 3 cases are still maintaining initial complete remission more than 3 years.

Topics: Adolescent; Adult; Aged; Antineoplastic Agents; Cytarabine; Daunorubicin; Drug Therapy, Combination; Female; Humans; Leukemia; Leukemia, Erythroblastic, Acute; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Middle Aged; Prednisolone; Remission, Spontaneous

Eleven adults with refractory leukemia treated with a combination of 6-mercaptopurine and Adriamycin developed hepatic dysfunction manifested by elevations of serum total bilirubin, alkaline phosphatase, and glutamic oxaloacetic transaminase. Liver tissue obtained at necropsy showed intrahepatic cholestasis (eight cases), hepatocellular necrosis (ten cases), leukemic infiltration (two cases), and fatty change (nine cases). Neither this frequency nor severity of hepatocellular destruction has hitherto been associated with 6-mercaptopurine at the dose levels used in this study, nor has Adriamycin previously been found to be hepatotoxic. It is postulated that Adriamycin potentiated the hepatotoxicity of 6-mercaptopurine in these patients.

Topics: Adult; Chemical and Drug Induced Liver Injury; Doxorubicin; Drug Synergism; Drug Therapy, Combination; Humans; Hyperbilirubinemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Liver Diseases; Mercaptopurine

The results of treatment of 84 acute leukaemia patients during a 15-year period are reported. Sixty-three of the patients suffered from acute myeloid leukaemia, 14 had blastic crisis of chronic leukaemia and 7 had acute myelomonocytic leukaemia. Administration of prednisolone + purinethol, prednisolone + vincristine, and prednisolone + vincristine + purinethol combinations resulted in partial remission. The best results were achieved with the combination ARA-C + thioguanine + prednisolone, which produced complete remission in 2 out of 8 cases. One patient was refractory to this treatment.

Topics: Adolescent; Adult; Aged; Antineoplastic Agents; Child; Cytarabine; Drug Therapy, Combination; Humans; Leukemia, Myeloid, Acute; Mercaptopurine; Middle Aged; Prednisolone; Remission, Spontaneous; Thioguanine; Vincristine

The quality of life in leukaemia is as important as its quantity. In fifty-one patients the quality and quantity of life were improved by less aggressive treatment than is usual. By not trying to induce complete remission at all costs, the mobidity and early mortality were reduced and at least an equivalence in survival was obtained.

Topics: Acute Disease; Adolescent; Adult; Aged; Allopurinol; Bacterial Infections; Cytarabine; Daunorubicin; Drug Therapy, Combination; Focal Infection, Dental; Follow-Up Studies; Humans; Length of Stay; Leukemia, Myeloid, Acute; Mercaptopurine; Middle Aged; Philosophy; Quality of Life; Remission, Spontaneous

Problems of maintaining therapy for acute myelocytic leukemias in adults are discussed. The analysis of the maintaining therapy in 22 patients affected with an acute myelocytic leukemia and living for more than 6 months revealed that the interval therapy with a high dosage of cytostatic combinations in the sense of the COAP scheme is preferable compared with the daily administration of 6-mercaptopurin, in addition methotrexate twice a week. Reasons for this are discussed.

Topics: Cyclophosphamide; Cytarabine; Drug Therapy, Combination; Female; Humans; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Methotrexate; Middle Aged; Prednisone; Remission, Spontaneous; Vincristine

After a chronic phase, the average duration of which in this series was 38 months, the acute phase of myeloid leukemia was very short, not exceeding 7 months. The clinical signs which suggest an acute exacerbation are, in order of importance, increase in the volume of the spleen, changes in general health, fever. The blood signs, which are often found later than the clinical signs, are increased white cell count, anemia and marrow leukoblastosis higher than 20%. The laboratory criteria of acute exacerbation are of lesser importance. Chemotherapy gives very poor results at this stage.

Topics: Alkaline Phosphatase; Female; Fever; Humans; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukocytes; Male; Mercaptopurine; Methotrexate; Middle Aged; Prednisone; Splenomegaly

Although definite improvement in the treatment of acute myelogenous leukemia has taken place, the outlook for patients remains grim. The current aggressive approach to treatment, entailing a program of chemotherapy which almost invariably produces bone marrow aplasia and considerable toxicity, has been the subject of some controversy. Selected aspects of management are discussed.

Topics: Adrenal Cortex Hormones; Anti-Bacterial Agents; Antineoplastic Agents; Blood Transfusion; Cell Division; Cyclophosphamide; Cytarabine; Drug Evaluation; Drug Synergism; Drug Therapy, Combination; Humans; Infection Control; Kinetics; Leukemia, Myeloid, Acute; Mercaptopurine; Methotrexate; Mycoses; Prednisone; Pseudomonas Infections; Remission, Spontaneous; Thioguanine; Vincristine

Topics: Allopurinol; Cytarabine; Guanosine; Humans; Leukemia, Myeloid, Acute; Mercaptopurine; Nucleosides; Uridine

A total of 114 previously untreated patients with myeloblastic leukemia was included in a sequential therapy protocol. Daunorubicin, vincristine, and prednisone were employed for the first 3 weeks, followed by two or more 5-day courses of cytosine arabinoside and 6-mercaptopurine; there was a 5-day rest between courses. Maintenance therapy was as follows: the continuing 6-mercaptopurine and methotrexate treatment was interrupted every 30 days for sequential reinforcement courses consisting of one dose of daunorubicin and vincristine and 7 days of prednisone, or by a 5-day course of cytosine arabinoside plus 6-mercaptopurine. Of the 114 patients, 48 obtained complete remission, 14 had partial remission, 16 failed to respond, and 36 died during the course of treatment. The remission rate in children (under 16) was 57%; in adults (16-45) 54%; and in those over 45, 19%. The difference in the incidence of complete remission in patients under 45 and those over 45 was statistically significant (p less than 0.01). The median duration of complete remission was 8 months: 12 months in children and 5 months in adults. The over-all survival rate was 4 months: 13 months for patients with complete remission, 4 months for those with partial remission, and 1 month for patients who did not respond to therapy. The difference in survival of those with complete remission and all the others was significant (p less than 0.01).

Topics: Adolescent; Adult; Age Factors; Antineoplastic Agents; Child; Cytarabine; Daunorubicin; Drug Therapy, Combination; Humans; Leukemia, Myeloid, Acute; Mercaptopurine; Methotrexate; Middle Aged; Prednisone; Remission, Spontaneous; Time Factors; Vincristine

Topics: Administration, Oral; Adolescent; Alkaloids; Antineoplastic Agents; Carbazoles; Child; Cytarabine; Daunorubicin; Drug Therapy, Combination; Female; Humans; Injections, Intravenous; Leukemia, Myeloid, Acute; Mercaptopurine; Methyl Ethers; Prednisone; Remission, Spontaneous; Time Factors

16 courses of an 8-drug regimen including daunomycin, vincristine, cytosinearabinoside, thioguanine, methotrexate, cyclophosphamide, prednisolone and hydroxyurea, and 12 courses of a 7-drug regimen including the same drugs minus hydroxyurea were administered in 16 otherwise therapy-resistant cases of acute myeloid leukaemia. In spite of a significant and rapid reduction of the leukaemic cell-mass in all the cases treated, only two brief minimal remissions were obtained. The main toxic effect was myelosuppression. However, the treatment was associated with a high frequency of mucosal ulcerations of the oesophagus and stomach, and it cannot be excluded that the latter complication may be drug-related.

Topics: Adolescent; Adult; Aged; Candidiasis; Cyclophosphamide; Cytarabine; Daunorubicin; Drug Resistance; Drug Therapy, Combination; Esophagitis, Peptic; Female; Humans; Hydroxyurea; Leukemia, Myeloid, Acute; Leukocyte Count; Leukopenia; Male; Mercaptopurine; Methotrexate; Middle Aged; Prednisolone; Stomach Ulcer; Thioguanine; Vincristine

Topics: Adolescent; Adult; Aged; Antineoplastic Agents; Cyclophosphamide; Cytarabine; Drug Therapy, Combination; Female; Humans; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Middle Aged; Prednisone; 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

During a 7 1/2-yr period we monitored a chromosomally aberrant cell line in a woman with acute granulocytic leukemia (AGL) whose disease followed a rather unusual course. Her initial remission induced with 6-mercaptopurine (6-MP) and prednisone was maintained for 52 mo with biweekly doses of methotrexate (MTX) given orally. Because signs of liver dysfunction occurred, maintenance therapy was stopped. After 15 mo without chemotherapy, she suffered her first relapse (5 yr 7 mo after the initial diagnosis). A second remission, again induced with 6-MP and prednisone, was maintained for 1 yr, after which a second relapse occurred. Another remission lasting for only 4 mo was followed by a relapse of the leukemic process which led to her death. Cytogenetic studies of marrow cells and peripheral blood at the time of her initial diagnosis showed abnormal stem lines with characteristic chromosome markers. A small percentage of malignant cells bearing these markers persisted in her marrow during the years of her prolonged remission. At the time of her first relapse, 75% of her marrow cells had the marker karyotype, and at the time of her death (7 1/2 yr after the leukemia was diagnosed) all analyzable marrow metaphases had the characteristic chromosome changes.

Topics: Adolescent; Bone Marrow; Bone Marrow Cells; Cells, Cultured; Chromosome Aberrations; Fatty Liver; Female; Humans; Karyotyping; Leukemia, Myeloid, Acute; Liver; Mercaptopurine; Mitosis; Necrosis; Prednisone; Remission, Spontaneous

Eighteen children with acute myeloid leukemia have been treated with a four-drug protocol using cytosine arabinoside, daunorubicin, prednisolone, and mercaptopurine or thioguanine. The initial remission rate overall was 78%. Of 15 children who completed a week's treatment, i.e. one complete cycle, 14 entered complete remission (93%). The median survival was 7 months, and the median survival for those entering remission was 12 1/2 months.

Topics: Antineoplastic Agents; Child; Child, Preschool; Cytarabine; Daunorubicin; Drug Therapy, Combination; Female; Humans; Infant; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Prednisolone; Remission, Spontaneous; Thioguanine

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 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; Ampicillin; Antibodies, Heterophile; Bone Marrow Examination; Cloxacillin; Female; Humans; Infectious Mononucleosis; Leukemia, Myeloid, Acute; Liver Function Tests; Mercaptopurine; Methotrexate; Prednisone; 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: Adult; Asparaginase; Betamethasone; Cytarabine; Daunorubicin; Drug Therapy, Combination; Humans; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Methotrexate; Spinal Cord Compression; Spinal Neoplasms

Topics: Adolescent; Adult; Age Factors; Aged; Child; Daunorubicin; Female; Humans; Hypersensitivity, Delayed; Immunity, Cellular; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Methotrexate; Middle Aged; Nitrobenzenes; Prednisone; Prognosis; Remission, Spontaneous; Sex Factors; Skin Tests; Vincristine

Topics: Age Factors; Bone Marrow Examination; Cytarabine; Daunorubicin; Drug Therapy, Combination; Humans; Hydroxyurea; Leukemia, Myeloid, Acute; Mercaptopurine; Nitrosourea Compounds; Prednisone; Remission, Spontaneous; Thioguanine; Vincristine

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: Adolescent; Adult; Age Factors; Azauridine; Child; Child, Preschool; Cytarabine; Drug Therapy, Combination; Female; Hepatomegaly; Humans; Leukemia, Myeloid, Acute; Liver; Lymph Nodes; Male; Mercaptopurine; Remission, Spontaneous; Spleen; Splenectomy; Splenomegaly; 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: Aminopterin; Antimetabolites; Azaguanine; Cytarabine; DNA, Neoplasm; Humans; Immunity, Cellular; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Mercaptopurine; Purines; Quinazolines; RNA, Neoplasm

Topics: Blood Transfusion; Female; Humans; Leukemia, Myeloid, Acute; Mercaptopurine; Middle Aged; Neoplasm Regression, Spontaneous; Prednisone; Prognosis; Time Factors

Topics: Cytarabine; Daunorubicin; Drug Synergism; Glyoxal; Humans; Leukemia, Myeloid, Acute; Mercaptopurine; Remission, Spontaneous

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

Topics: Autoradiography; Bone Marrow Cells; Cell Adhesion; Cell Division; Cell Separation; Cells, Cultured; Culture Media; Cytarabine; Daunorubicin; Freezing; Humans; Lectins; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukocytes; Male; Mercaptopurine; Middle Aged; Prednisone; Radiation Effects; Thymidine; Tritium; Ultrafiltration

Topics: Adolescent; Adult; Age Factors; Aged; Child; Child, Preschool; Cytarabine; Daunorubicin; Drug Therapy, Combination; Humans; Infant; Leukemia, Myeloid, Acute; Mercaptopurine; Middle Aged; Prednisone; Remission, Spontaneous; Vincristine

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: Antineoplastic Agents; Busulfan; Child; Child, Preschool; Cytarabine; Daunorubicin; Drug Therapy, Combination; Female; Humans; Infant; Infant, Newborn; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Methotrexate; Thioguanine; Vincristine

Topics: Adolescent; Adult; Aged; Anhydrides; Cyclophosphamide; Cytarabine; Daunorubicin; Female; Humans; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Middle Aged; Prednisolone

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: 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: Adolescent; Adult; Antineoplastic Agents; Cyclophosphamide; Cytarabine; Daunorubicin; Drug Therapy, Combination; Humans; Leukemia, Myeloid, Acute; Mercaptopurine; Middle Aged; Prednisolone; Remission, Spontaneous; Thioinosine

Topics: Anemia, Sideroblastic; Bone Marrow Examination; Cytarabine; Female; Humans; Immunodiffusion; Immunoelectrophoresis; Immunoglobulins; Iron; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Male; Melphalan; Mercaptopurine; Middle Aged; Multiple Myeloma; Muramidase; Precancerous Conditions; Prednisone; Staining and Labeling; Vincristine

Topics: Cytarabine; Female; Humans; Leukemia, Myeloid, Acute; Male; Melphalan; Mercaptopurine; Middle Aged; Multiple Myeloma

Topics: Adolescent; Adult; Aged; Busulfan; Histocytochemistry; Humans; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukocytes; Mercaptopurine; Methotrexate; Middle Aged; Tetrahydrofolate Dehydrogenase

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

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: Cytarabine; Drug Synergism; Humans; Leukemia, Erythroblastic, Acute; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Mercaptopurine

Topics: Abortion, Spontaneous; Abortion, Therapeutic; Adult; Blood Coagulation Tests; Blood Platelets; Blood Transfusion; Female; Humans; Labor, Induced; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Mercaptopurine; Prednisolone; Pregnancy; Pregnancy Complications, Hematologic

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: Adolescent; Adult; Bone Marrow Cells; Bone Marrow Examination; Cell Count; Cell Division; Child; Clone Cells; Culture Techniques; Cytarabine; Daunorubicin; Drug Therapy, Combination; Embryo, Mammalian; Female; Humans; Kidney; Leukemia, Myeloid, Acute; Leukocytes; Male; Mercaptopurine; Methotrexate; Middle Aged; Prednisolone; Remission, Spontaneous; Thioguanine; Vincristine

Topics: Administration, Oral; Adult; Aged; Child; Cytarabine; Drug Therapy, Combination; Evaluation Studies as Topic; Female; Humans; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Middle Aged; 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: 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: 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: Adult; Anemia, Neonatal; Female; Humans; Infant, Newborn; Infant, Premature, Diseases; Leukemia, Myeloid, Acute; Maternal-Fetal Exchange; Mercaptopurine; Pregnancy; Pregnancy Complications, Hematologic

Topics: Adenine; Allopurinol; Bone Marrow; Bone Marrow Cells; Carbon Radioisotopes; Cell-Free System; Chromatography, Paper; Formates; Guanine Nucleotides; Humans; Hypoxanthines; Kinetics; Leucovorin; Leukemia; Leukemia, Myeloid, Acute; Leukocytes; Ligases; Mercaptopurine; Pentosephosphates; Pentosyltransferases; Spectrophotometry, Ultraviolet; Tetrahydrofolates

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

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: Adult; Anemia, Aplastic; Benzene; Environmental Exposure; Humans; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Methotrexate; Middle Aged; Occupational Diseases; Shoes

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

Topics: Cytarabine; Daunorubicin; Evaluation Studies as Topic; Humans; Leukemia, Myeloid, Acute; Mercaptopurine; Prednisone; Remission, Spontaneous

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; Adult; Aged; Child; Child, Preschool; Cyclophosphamide; Cytarabine; Daunorubicin; Female; Humans; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Middle Aged; Vincristine

Topics: Aged; Autopsy; Humans; Leukemia, Myeloid, Acute; Leukocyte Count; Leukocytes; Male; Mercaptopurine; Methotrexate; Middle Aged; Prednisone; Pulmonary Artery; Pulmonary Circulation; Pulmonary Embolism; Pulmonary Veins; Vincristine

Topics: Adolescent; Adult; Breast Neoplasms; Citrates; Female; Gallium; Humans; Leukemia, Myeloid, Acute; Mercaptopurine; Methotrexate; Nasopharyngeal Neoplasms; Prednisone; Radionuclide Imaging; Vincristine

Topics: Adult; Cyclophosphamide; Female; Humans; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Prednisolone; Time Factors

Topics: Adult; Cyclophosphamide; Cytarabine; Humans; Leukemia, Myeloid, Acute; Mercaptopurine; Prednisolone

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: 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: 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: Acute Disease; Administration, Oral; Adolescent; Adult; Age Factors; Aged; Amino Sugars; Antibiotics, Antineoplastic; Antineoplastic Agents; Cytarabine; Drug Synergism; Female; Follow-Up Studies; Glycosides; Humans; Injections, Intravenous; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Middle Aged; Prednisolone; Pregnancy; Remission, Spontaneous; Time Factors

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: Adolescent; Adult; Anti-Bacterial Agents; Blood Platelets; Blood Transfusion; Female; Hemorrhage; Humans; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Middle Aged; Prednisolone; Remission, Spontaneous

Topics: Adolescent; Adult; Aged; Alopecia; Ampicillin; Anemia, Aplastic; Antibiotics, Antineoplastic; Blood Platelets; Blood Transfusion; Cardiomyopathies; Cephaloridine; Electrocardiography; Female; Heart; Humans; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Middle Aged; Paresthesia; Remission, Spontaneous; Sulfamethoxazole; Thrombocytopenia; Trimethoprim

Topics: Blood Protein Disorders; Blood Protein Electrophoresis; Blood Transfusion; Bone Marrow; Bone Marrow Cells; Bone Marrow Examination; Chromosome Aberrations; Chromosomes, Human, 1-3; Chromosomes, Human, 6-12 and X; Female; Fluorescent Antibody Technique; Humans; Immunodiffusion; Immunoelectrophoresis; Immunoglobulin G; Karyotyping; Leukemia, Myeloid, Acute; Mercaptopurine; Middle Aged; Mosaicism; Plasma Cells; Prednisolone; Thalassemia

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

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: Adult; BCG Vaccine; Cell Division; Cytarabine; Daunorubicin; Humans; Injections, Intravenous; Leukemia, Myeloid, Acute; Mercaptopurine; Methotrexate; Neoplasm Transplantation; Transplantation, Autologous; Transplantation, Homologous

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: Adult; Asparaginase; Blood Transfusion; Bone Marrow; Cytarabine; Daunorubicin; Erythrocytes; Erythrocytes, Abnormal; Female; Humans; Iron; Leukemia, Myeloid, Acute; Mercaptopurine; Prednisone; Remission, Spontaneous

Topics: Anemia, Hemolytic, Autoimmune; Anti-Bacterial Agents; Antimetabolites; Blood Specimen Collection; Bone Marrow Diseases; Busulfan; Chromosome Aberrations; Diuretics; Hodgkin Disease; Humans; Karyotyping; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukemoid Reaction; Mercaptopurine; Prednisone; Specimen Handling; Thrombocytopenia; Time Factors

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: Adult; Aged; Antibodies; Antigens; Cyclophosphamide; Cytarabine; Female; Hemocyanins; Humans; Hypersensitivity, Delayed; Immunity, Cellular; Immunologic Deficiency Syndromes; Immunosuppression Therapy; Lectins; Leukemia, Myeloid, Acute; Leukocyte Count; Lymphocyte Activation; Lymphocytes; Male; Mercaptopurine; Methotrexate; Prednisone; Prognosis; Remission, Spontaneous; Skin Tests; Thioguanine; Vincristine

Topics: Betamethasone; Bone Marrow Examination; Candidiasis; Daunorubicin; Humans; Leukemia; Leukemia, Myeloid, Acute; Male; Meninges; Meningitis; Mercaptopurine; Methotrexate; Middle Aged; Remission, Spontaneous

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

Topics: Antineoplastic Agents; Bronchial Neoplasms; Carcinoma, Bronchogenic; Drug Tolerance; Glycine; Humans; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Mercaptopurine; Purines; Sulfides; Valerates

Topics: Antineoplastic Agents; Bone Marrow; Child; Child, Preschool; Cytidine; Drug Tolerance; Humans; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukocyte Count; Leukocytes; Mercaptopurine; Prednisone; Remission, Spontaneous; Thiazines; Vincristine

Topics: Acute Disease; Adolescent; Adult; Aged; Azathioprine; Female; Humans; Infections; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Middle Aged; Prednisone; 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: Acute Disease; Adolescent; Adult; Aged; Azathioprine; Female; Humans; Infections; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Middle Aged; Prednisone; Remission, Spontaneous

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

Topics: Acidosis; Humans; Lactates; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Middle Aged; 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: Aged; Blood Cell Count; Blood Platelets; Blood Transfusion; Electrocardiography; Hematocrit; Humans; Hyperkalemia; Leukemia, Myeloid, Acute; Leukocyte Count; Leukocytes; Male; Mercaptopurine; Methotrexate; Potassium; Prednisone; Vincristine

Topics: Autopsy; Blood Platelets; Erythrocyte Count; Female; Hemoglobinometry; Humans; Leukemia, Myeloid, Acute; Leukocyte Count; Mercaptopurine; Middle Aged; Prednisone

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: 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: Adult; Antineoplastic Agents; Blood Coagulation Disorders; Disseminated Intravascular Coagulation; Heparin; Humans; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Methotrexate; Prednisone; 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: 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: Adolescent; Adult; Aged; Cytarabine; Female; Humans; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Middle Aged

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: Adrenal Glands; Adult; Cicatrix; Diabetes Insipidus; Hemorrhage; Humans; Leukemia, Myeloid, Acute; Leukopenia; Male; Mercaptopurine; Metyrapone; Pituitary Gland, Posterior; Pituitary-Adrenal Function Tests; Sodium Chloride; Specific Gravity; Urine

Topics: Adolescent; Adult; Antibiotics, Antineoplastic; Antineoplastic Agents; Bone Marrow Cells; Humans; Injections, Intravenous; Leukemia, Myeloid, Acute; Mercaptopurine; Methotrexate

Topics: Aged; Female; Herpes Simplex; Humans; Leukemia, Myeloid, Acute; Mercaptopurine; Prednisone

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

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: Adult; Afibrinogenemia; Aged; Anticoagulants; Antifibrinolytic Agents; Blood Coagulation Disorders; Blood Coagulation Tests; Blood Platelets; Blood Transfusion; Carcinoid Tumor; Female; Fibrinogen; Fibrinolysis; History, 19th Century; History, 20th Century; Humans; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Mitomycins; Prednisone; Steroids

Topics: Glucocorticoids; Humans; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Mercaptopurine

Topics: Adult; Afibrinogenemia; Aged; Anemia; Antineoplastic Agents; Child; Cytarabine; Daunorubicin; Humans; Hydroxyzine; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukopenia; Mercaptopurine; Methotrexate; Middle Aged; Polycythemia Vera; Prednisone; Primary Myelofibrosis; Splenomegaly; Vincristine

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: Androgens; Anemia; Blood Cell Count; Blood Transfusion; Bone Marrow Examination; Cyclophosphamide; Hematocrit; Hemoglobins; Hemoglobinuria, Paroxysmal; Hemolysis; Humans; Iron; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Middle Aged; Plasma; Prednisone; Vincristine

Topics: Adolescent; Adult; Age Factors; Female; Humans; Leukemia, Myeloid, Acute; Leukocyte Count; Male; Mercaptopurine; Middle Aged; Sex Factors

Topics: Antimetabolites; Blood Cells; Cell Line; Culture Techniques; Cytarabine; Fluorouracil; Humans; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Mercaptopurine; Methotrexate; Mitosis; Neoplasms

Topics: Bone Marrow Examination; Cerebrospinal Fluid; Child, Preschool; Electroencephalography; Female; Humans; Infant; Injections, Spinal; Leukemia, Myeloid, Acute; Meningitis; Mercaptopurine; Methotrexate

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: Animals; Antineoplastic Agents; Burkitt Lymphoma; Culture Techniques; Humans; Leukemia; Leukemia L1210; Leukemia, Experimental; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukocytes; Mercaptopurine; Methotrexate; Mice; Prednisolone; 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: Adult; Bilirubin; Blood Cell Count; Blood Transfusion; Bone Marrow Examination; Coombs Test; Female; Hematocrit; Hemoglobinuria, Paroxysmal; Hemorrhage; Humans; Hysterectomy; Leukemia, Myeloid, Acute; Mercaptopurine; Oral Hemorrhage; Osmotic Fragility; Prednisone; Pyoderma; Reticulocytes; Staphylococcus; Tooth Extraction

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: Adolescent; Adrenocorticotropic Hormone; Adult; Age Factors; Alkylating Agents; Colchicine; Female; Follow-Up Studies; Glucocorticoids; Humans; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Methylprednisolone; Middle Aged; Prednisone; Prognosis; Spironolactone; Triamcinolone Acetonide; Triazines; Uracil

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

Topics: Adolescent; Adult; Aged; Child; Child, Preschool; Female; Glucocorticoids; Humans; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Middle Aged; Myeloproliferative Disorders; Thrombocythemia, Essential

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: Aeromonas; Child; Female; Humans; Leukemia, Myeloid, Acute; Mercaptopurine; Osteomyelitis; Penicillin Resistance; Penicillins; Sepsis; Tetracycline

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

Topics: Adolescent; Adult; Bone Marrow; Bone Marrow Cells; Female; Humans; Leukemia, Myeloid, Acute; Male; Mercaptopurine

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

Topics: Aged; Blood Cell Count; Blood Transfusion; Bone Marrow Examination; Busulfan; Female; Humans; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Middle Aged; Prednisolone; Prognosis

Topics: Adolescent; Aeromonas; Cyclophosphamide; Cytarabine; Female; Humans; Immunosuppressive Agents; Joint Diseases; Leukemia, Myeloid, Acute; Mercaptopurine; Methotrexate; Prednisone; Sepsis; Vincristine

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: Bone Marrow; Chloramphenicol; Female; Hematocrit; Hemoglobinometry; Humans; Leukemia, Myeloid, Acute; Leukocyte Count; Leukopenia; Lupus Erythematosus, Systemic; Mercaptopurine; Middle Aged; Pneumonia; Prednisone

Topics: Acute Disease; Adolescent; Adult; Aged; Child; Child, Preschool; Dexamethasone; Female; Humans; Infant; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Middle Aged; Prednisolone

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: Cytarabine; Humans; Infusions, Parenteral; Leukemia, Myeloid, Acute; Mercaptopurine

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: Aged; Carcinoma; Chromosome Aberrations; Chromosome Disorders; Diploidy; Humans; Karyotyping; Laryngeal Neoplasms; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Mitosis; Prednisone

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: Acute Disease; Antineoplastic Agents; Child, Preschool; Cyclophosphamide; Humans; Leukemia, Myeloid, Acute; Mercaptopurine; Methotrexate; Prednisone; Prognosis; Vinblastine

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

Topics: Aged; Hematocrit; Humans; Leukemia, Myeloid, Acute; Leukocyte Count; Mercaptopurine; Middle Aged; Prednisone

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

Topics: Allopurinol; Bone Marrow Diseases; Drug Synergism; Enzyme Therapy; Humans; Leukemia, Myeloid, Acute; Mercaptopurine; Myeloproliferative Disorders; Xanthine Oxidase

Topics: Adult; Anemia, Hemolytic; Diagnosis, Differential; Female; Humans; Leukemia, Erythroblastic, Acute; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Middle Aged; Prednisolone

Topics: Humans; Leukemia, Myeloid, Acute; Mercaptopurine

Topics: Agranulocytosis; Female; Humans; Leukemia, Myeloid, Acute; Mercaptopurine; Middle Aged; Proctitis

Topics: Cytoplasm; Giardia; Giardiasis; Humans; Intestinal Diseases, Parasitic; Leukemia, Myeloid, Acute; Mercaptopurine

Topics: Drug Therapy; Guanidines; Humans; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Mercaptopurine; Mitoguazone; Pyruvaldehyde; Toxicology

Topics: Adult; Child; Cyclophosphamide; Humans; Leukemia; Leukemia, Myeloid, Acute; Mercaptopurine; Methotrexate; Prednisone; Vincristine

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

Topics: Adrenal Cortex Hormones; Blood Cell Count; Blood Transfusion; Bone Marrow Examination; Eosinophils; Hemostatics; Humans; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Mercaptopurine; Pathology; Tetracycline; Thrombin; Vitamin B Complex

Topics: Bone Marrow Examination; Brain Neoplasms; Cerebrospinal Fluid Proteins; Humans; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Meninges; Mercaptopurine; Methotrexate; Neoplasms; Prednisone

Topics: Antineoplastic Agents; Glyoxal; Humans; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Mercaptopurine

Topics: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Mercaptopurine; Purines