mercaptopurine and Central-Nervous-System-Diseases

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

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

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

Topics: Abnormalities, Drug-Induced; Adolescent; Adult; Antineoplastic Agents; Busulfan; Carcinogens; Central Nervous System Diseases; Chemical and Drug Induced Liver Injury; Child; Female; Heart Diseases; Humans; Lung Diseases; Male; Menstruation Disturbances; Mercaptopurine; Methotrexate; Neoplasms; Neoplasms, Radiation-Induced; Pregnancy; Radiotherapy; Urinary Bladder Diseases

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

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

Topics: 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

The Pediatric Oncology Group (POG) acute leukemia in childhood (ALinC) 13 study tested two treatment regimens that used different CNS chemoprophylaxis for children older than 12 months with non-T, non-B acute lymphoblastic leukemia (ALL) and with no demonstrable CNS disease at diagnosis.. With the first regimen, standard (S), six injections of triple intrathecal chemotherapy (TIC), consisting of methotrexate (MTX), hydrocortisone (HC), and cytarabine (ara-C), were administered during intensification treatment and at every-8-week intervals throughout the maintenance phase for 17 additional doses. The second regimen, standard and MTX pulses (SAM), also specified six TICs during intensification, but substituted every-8-week pulses of intermediate-dose parenteral methotrexate (IDM; 1 g/m2) for the 17 maintenance TIC injections, with a low-dose intrathecal (IT) MTX boost administered with the first four maintenance IDM pulses. Otherwise, systemic therapy on regimen SAM was identical to regimen S. There were 1,152 patients randomized to the S and SAM regimens after stratification by risk group (age/leukocyte count) and immunophenotype.. The 5-year probabilities (+/- SE) of an isolated CNS relapse were regimen S: good risk (n = 381), 2.8% +/- 1.3%; poor risk (n = 196), 7.7% +/- 3.2%; good + poor risk (n = 577), 4.7% +/- 1.5%; regimen SAM: good risk (n = 388), 9.6% +/- 2.2%; poor risk (n = 187), 12.7% +/- 4.2%; good + poor risk (n = 575), 10.9% +/- 2.2%. In poor-risk patients, approximately one third of the isolated CNS relapses occurred before preventive CNS therapy was begun at week 9. Hence, regimen S has provided better CNS preventive therapy for both good- and poor-risk patients (P < .001 overall). The difference is statistically significant for good-risk patients (P < .001), but not for poor-risk patients (P = .20). Neither treatment has shown a significant advantage in terms of general outcome.. TIC injections extended throughout the intensification and maintenance periods are superior to IDM pulses for prevention of CNS leukemia. Our results with TIC seem comparable with those achieved with other contemporary methods of CNS preventative therapy. Thus, extended TIC affords a reasonable alternative to CNS irradiation plus upfront IT MTX for patients with B-progenitor ALL.

Topics: Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Central Nervous System Diseases; Cyclophosphamide; Cytarabine; Dose-Response Relationship, Drug; Humans; Hydrocortisone; Injections, Spinal; Leukemic Infiltration; Mercaptopurine; Methotrexate; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma; Prednisone; Risk Factors; Vincristine

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

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

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

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

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

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

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

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

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

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

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

Central nervous system (CNS) complications during treatment of childhood acute lymphoblastic leukemia (ALL) remain a challenging clinical problem. Outcome improvement with more intensive chemotherapy has significantly increased the incidence and severity of adverse events. This study analyzed the incidence of neurological complications during ALL treatment in a single pediatric institution, focusing on clinical, radiological, and electrophysiological findings. Exclusion criteria included CNS leukemic infiltration at diagnosis, therapy-related peripheral neuropathy, late-onset encephalopathy, or long-term neurocognitive defects. During a 9-year period, we retrospectively collected 27 neurological events (11%) in as many patients, from 253 children enrolled in the ALL front-line protocol. CNS complications included posterior reversible leukoencephalopathy syndrome (n = 10), stroke (n = 5), temporal lobe epilepsy (n = 2), high-dose methotrexate toxicity (n = 2), syndrome of inappropriate antidiuretic hormone secretion (n = 1), and other unclassified events (n = 7). In conclusion, CNS complications are frequent events during ALL therapy, and require rapid detection and prompt treatment to limit permanent damage.

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Central Nervous System; Central Nervous System Diseases; Child; Child, Preschool; Cyclophosphamide; Cytarabine; Daunorubicin; Electroencephalography; Female; Humans; Infant; Leukemic Infiltration; Magnetic Resonance Imaging; Male; Mercaptopurine; Methotrexate; Peripheral Nervous System Diseases; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prednisone; Retrospective Studies; Tomography, X-Ray Computed; Vincristine

Juvenile xanthogranuloma (JXG), one of the most common forms of Langerhans-dendritic cell proliferation in young children, usually presents as spontaneously regressing cutaneous lesions. JXG with systemic (extracutaneous) involvement is a rare histiocytic disorder in which significant morbidity and death may occur. The systemic type, especially combined with multiple central nervous system lesions in young children, has a very poor prognosis. The patient described here presented with disseminated disease including lungs, liver, kidneys, ribs, scalp, and central nervous system. The patient was treated with multiagent chemotherapy based on the Langerhans cell histiocytosis II treatment protocol. The regimen used included an additional intrathecal therapy with methotrexate and prednisolone to control central nervous system lesions. The patient was treated for 28 months and has been in remission for almost 5 years.

Topics: Central Nervous System Diseases; Combined Modality Therapy; Craniotomy; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Infant; Injections, Spinal; Liver Diseases; Lung Diseases; Mercaptopurine; Methotrexate; Paresis; Prednisolone; Skin Diseases; Vinblastine; Xanthogranuloma, Juvenile

Thirteen adult patients with histologically confirmed lymphoblastic lymphoma were treated with an intensive chemotherapy program consisting of induction with cyclophosphamide, adriamycin, vincristine, and prednisone (modified CHOP); consolidation and central nervous system (CNS) prophylaxis with methotrexate intrathecally and by high-dose intravenous injection, citrovorum factor and L-asparaginase; reinforcement with CHOP; and maintenance with 6-mercaptopurine and methotrexate. Treatment duration was 1 yr. A 14th patient with T-cell acute lymphoblastic leukemia was also treated at presentation by the same regimen. Thirteen patients had at least a mediastinal mass or abnormal cells in the bone marrow; one presented with CNS disease. The median age was 22 yr (range 16--50), and male--female ratio was 2.5:1. All patients had a rapid complete clinical response. Of the 13 patients without initial CNS disease, 4 have relapsed, 3 with primary CNS relapse and 1 with a recurrent abdominal mass. Five patients have died, 2 from drug toxicity, 2 from CNS relapse, and 1 from chronic myelogenous leukemia, which was diagnosed simultaneously with the lymphoblastic lymphoma. The median follow-up is 19 mo, and all patients have completed their planned therapy. At 3 yr, the actuarial survival is 61% and relapse-free survival is 56%.

Topics: Adolescent; Adult; Asparaginase; Central Nervous System Diseases; Cyclophosphamide; Doxorubicin; Female; Humans; Leucovorin; Leukemia, Myeloid; Lymphoma, Non-Hodgkin; Male; Mercaptopurine; Methotrexate; Middle Aged; Prednisone; Vincristine

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Topics: Adolescent; Antineoplastic Agents; Central Nervous System Diseases; Child; Dactinomycin; Humans; Leukemia; Mechlorethamine; Mercaptopurine; Methotrexate; Prednisone; Vincristine

Topics: Adolescent; Antineoplastic Agents; Asparaginase; Central Nervous System Diseases; Child; Cyclophosphamide; Cytarabine; Daunorubicin; Female; Humans; Injections, Intravenous; Leukemia; Male; Meninges; Mercaptopurine; Methotrexate; Prednisone; Vincristine

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

Topics: Antineoplastic Agents; Central Nervous System Diseases; Child; Clinical Laboratory Techniques; Drug Therapy; Headache; Humans; Intracranial Pressure; Leukemia; Mercaptopurine; Methotrexate; Neoplasms; Papilledema; Prednisone; Vomiting

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