thioguanine-anhydrous and Central-Nervous-System-Diseases

Topics: Adult; Alkaline Phosphatase; BCG Vaccine; Blood Transfusion; Bone Marrow Examination; Central Nervous System Diseases; Cytarabine; Daunorubicin; Diagnosis, Differential; Drug Combinations; Drug Therapy, Combination; Esterases; Humans; Immunotherapy; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Lymphocyte Transfusion; Meningitis; Microscopy, Electron; Neutrophils; Staining and Labeling; Subarachnoid Hemorrhage; Thioguanine

Although a large majority of adult patients with acute nonlymphocytic leukemia (ANLL) achieve complete remission with present day therapy, eventual relapse and death is the rule rather than the exception. In an effort to improve survival, an intensive maintenance therapy approach was evaluated in 86 patients with ANLL in remission (median age 47 years) entered on study from 1978 to 1982. One-third of patients in remission were randomized to chemotherapy alone, one-third to splenectomy in addition to chemotherapy, and one-third to immunotherapy in addition to chemotherapy. The chemotherapy, which was identical in the three arms of the study, consisted of cytosine arabinoside plus 6-thioguanine, each given at a dose of 100 mg/m2 every 12 hr for a variable number of days, to render the patient's marrow aplastic, and was repeated every three months for three or more years. Median remission duration for patients in all three study groups is 21 months, with 58% of patients remaining in remission at one year. Twenty-five per cent of complete remitters are in continuous complete remission five to nine years after beginning intensive maintenance therapy. The median duration of survival of remitters is 25 months. Neither splenectomy nor immunotherapy had additional impact on remission duration or survival. In comparison with the results of earlier studies at the same institution in patients with similar characteristics, using identical remission induction therapy but less intensive maintenance therapy (46 patients), there has been a significant improvement in remission duration (p less than 0.001) and a significant impact on survival (p = 0.03) attributable to the use of intensive maintenance therapy. Intensive maintenance therapy may cure some adult patients with ANLL.

Topics: Acute Disease; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Central Nervous System Diseases; Cytarabine; Evaluation Studies as Topic; Female; Follow-Up Studies; Humans; Immunotherapy; Leukemia; Male; Middle Aged; Neuraminidase; Remission Induction; Splenectomy; Thioguanine

Between 1978 and 1983, 1127 patients with de-novo acute myeloid leukaemia (AML) were entered into the Medical Research Council (MRC)'s 8th AML trial. All received the same induction therapy consisting of daunorubicin, cytarabine, and 6-thioguanine--DAT (1 + 5). The 67% who entered complete remission were randomised to consolidation with two or six further courses of DAT. Adults under the age of 55 were randomised for central nervous system (CNS) prophylaxis with intrathecal cytarabine and methotrexate. Finally, those still in remission after 1 year of cytarabine and 6-thioguanine (AT) maintenance were randomised to receive either late intensification with cyclophosphamide, vincristine, cytarabine, and prednisolone (COAP) or continued AT. The median survival for the whole group was 12 months; the median duration of first remission was 15 months, with relapse-free survival at 5 years estimated at 18%. The factors most strongly associated with poor survival were performance status and age at presentation, but even among those over 60 years of age, half went into remission. Six courses of DAT consolidation gave a small advantage over two courses in reducing the number of late relapses but no significant survival advantage. Late intensification showed a marginally significant advantage over continued AT maintenance. The incidence of CNS relapse was low and unaffected by prophylaxis. The second remission rate varied from 10% when the first remission was shorter than 6 months to 61% when it had continued for more than 2 years. 40 patients received histocompatible allogeneic bone-marrow transplants in first remission. There was a high procedure-related death rate, particularly among patients over 30 years of age. Thus, initially at least, the transplanted group had shorter survival than a comparable group of chemotherapy-treated patients. Treatment specifications remained unchanged throughout the trial but those enrolled in the later half of the trial had a better (p = 0.003) survival.

Topics: Adolescent; Adult; Age Factors; Aged; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Central Nervous System Diseases; Child; Child, Preschool; Clinical Trials as Topic; Cytarabine; Daunorubicin; Drug Administration Schedule; Humans; Infant; Leukemia, Myeloid, Acute; Middle Aged; Neoplasm Recurrence, Local; Neoplasms; Prognosis; Random Allocation; Thioguanine

The Eastern Cooperative Oncology Group conducted a randomized study to determine the efficacy of consolidation therapy in prolonging the duration of complete remission (CR) in adults with acute nonlymphocytic leukemia (ANLL). Induction chemotherapy with daunorubicin, cytosine arabinoside, and 6-thioguanine (DAT) yielded CR in 65% of 283 patients with ANLL, aged 16-69. For patients aged 60-69, the CR rate was 58%. Of 184 patients in CR, 146 patients were then randomized to receive either maintenance therapy with weekly cytosine arabinoside and 6-thioguanine alone (69 patients) or two courses of reduced doses of DAT 1 mo apart, before commencing the same maintenance program (77 patients). Consolidation therapy resulted in hematologic toxicity, but was not lethal in any of the eligible patients. Patients receiving consolidation plus maintenance therapy experienced a longer CR duration (40 wk) and disease-free survival at 2 yr (28%) than did those patients receiving maintenance therapy alone (34 wk and 14%, respectively). These differences are not statistically significant. These results suggest that approaches to consolidation therapy employing reduced doses of the induction therapy regimen can have, at best, only a small benefit. For consolidation therapy to provide substantial improvement in CR duration, intensive regimens with non-cross-resistant drugs will be required.

Topics: Acute Disease; Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Diseases; Central Nervous System Diseases; Chemical and Drug Induced Liver Injury; Cytarabine; Daunorubicin; Drug Administration Schedule; Drug Evaluation; Female; Humans; Leukemia; Male; Middle Aged; Random Allocation; Thioguanine; United States

Sixty-six newly diagnosed patients with acute nonlymphocytic leukemia received either daunorubicin alone or a combination of daunorubicin, cytosine arabinoside, 6-thioguanine, and pyrimethamine for remission-induction therapy. The two treatment groups were comparable with respect to the two major prognostic factors in this disease, which were age and presence or absence of infection on admission. The two therapies produced similar results with respect to CR rate and median survival results. Single-agent therapy was associated with less frequent utilization of hospital inpatient facilities and fewer platelet transfusions. The four-drug combination did not decrease the incidence of meningeal leukemia. Patients who achieved CR were treated with two half-dose consolidation courses of the successful remission-induction regimen. Subsequently, all patients received cyclophosphamide and guanazole monthly for maintenance therapy. Median durations of remission for both induction-treatment groups were similar (6.8 and 5.6 mos). The therapeutic results with the single agent in this study were not inferior to those obtained with the drug combination tested, as well as most other previously reported combinations of antileukemic drugs.

Topics: Acute Disease; Aged; Antineoplastic Agents; Bone Marrow; Central Nervous System Diseases; Cyclophosphamide; Cytarabine; Daunorubicin; Drug Therapy, Combination; Female; Guanazole; Humans; Leukemia; Leukemia, Myeloid, Acute; Male; Meninges; Middle Aged; Pyrimethamine; Remission, Spontaneous; Skin Tests; Thioguanine

Between 1969-1973, 75 consecutive children under the age of 15 years with acute lymphoblastic leukemia were treated with a multiple-drug regimen (L-2). Prophylaxis for meningeal leukemia was limited to the repeated intrathecal injections of methotrexate. Seventy-four patients achieved remission; the duration of remissions could be evaluated only for 70. Relapse terminated complete remission within 1-54 months in 21 children. Four of these relapses were confined to the central nervous system. Forty-nine patients continue in complete remission from 23 to 63 months. Chemotherapy has been discontinued in 29 children, and 25 of these remain without evidence of recurrence for 2-27 months posttreatment.

Topics: Adolescent; Antineoplastic Agents; Asparaginase; Central Nervous System Diseases; Child; Child, Preschool; Cyclophosphamide; Cytarabine; Daunorubicin; Drug Therapy, Combination; Female; Humans; Hydroxyurea; Infant; Injections, Spinal; Leukemia, Lymphoid; Male; Methotrexate; Nitrosourea Compounds; Prednisone; Remission, Spontaneous; Thioguanine; Vincristine

Cytarabine is an effective agent in the treatment of acute leukemia. Since its approval by The Food and Drug Administration in 1969, the clinical effectiveness of this drug has increased as knowledge of its pharmacologic and biologic properties has been translated into clinical trials. A complete remission rate of greater than 50% can be achieved when cytarabine is used in combination with other agents in the treatment of adult acute myeloblastic leukemia. Remissions occur only after the development of significant bone-marrow hypoplasia, and the care of patients through this period of pancytopenia requires elaborate supportive techniques and facilities. The role of cytarabine in the treatment of acute lymphoblastic leukemia and lymphoma is still under clinical investigation and appears promising. Because the clinical effectiveness of cytarabine in the treatment of nonmalignant diseases has not been proved, its use in these disorders must be considered investigational and weighed against the serious bone-marrow suppression and potential long-term hazards of this drug.

Topics: Acute Disease; Adult; Animals; Bone Marrow Diseases; Central Nervous System Diseases; Cyclophosphamide; Cytarabine; Daunorubicin; DNA, Neoplasm; Drug Therapy, Combination; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Lymphoma; Prednisone; Remission, Spontaneous; Thioguanine; Vincristine; Virus Diseases