thioguanine-anhydrous and Meningeal-Neoplasms

Chemotherapy of adults with acute nonlymphocytic leukemia has improved in recent years, yielding complete remissions in 65 per cent and cure in 10 to 15 per cent of all treated patients. Allogeneic bone marrow transplantation cures approximately one half of eligible young patients who gain an initial remission with chemotherapy. Autologous bone marrow transplantation may ultimately prove to be of value for the large numbers of patients who are over 40 years of age or who lack histocompatible siblings. Current investigative approaches in all these areas, based on insights into the pathophysiology of disease discussed in this article, should enhance the outcome for affected patients in the next decade.

Topics: Acute Disease; Adult; Aged; Antigens, Neoplasm; Antigens, Surface; Antineoplastic Combined Chemotherapy Protocols; Chromosome Aberrations; Cytarabine; Daunorubicin; Humans; Leukemia; Meningeal Neoplasms; Methotrexate; Middle Aged; Thioguanine

Childrens Cancer Group 123 was a trial of intensive multidrug chemotherapy as well as cranial irradiation and bulk disease irradiation in children with acute lymphoblastic leukemia with lymphomatous presentation (bulk disease and either T-cell phenotype, high white blood count, or absence of anemia), a poor prognostic group with an increased risk of central nervous system (CNS) and other extramedullary recurrence.. Three hundred eight patients without CNS disease were randomized among three regimens: A--BFM chemotherapy (designed for high risk ALL patients) with 1800 cGy cranial irradiation; B--LSA2L2 chemotherapy (designed for non-Hodgkins lymphoma patients) with 1800 cGy cranial irradiation and 1500 cGy to nonabdominal bulk disease; C--Reg B without cranial irradiation. All patients received intrathecal methotrexate throughout therapy. Radiation treatment records were reviewed.. With a minimum 52-month follow-up, Regimen B and C patients had 5-year actuarial CNS relapses of 7% and 17% (p = 0.01) and event-free survivals of 53% and 39% (p = 0.04). Patients with white blood count < 50,000/mm3 did not benefit from cranial irradiation. Regimen A patients had the same CNS relapse rate as Regimen B patients but an improved event-free survival. Regimen B and C patients with large mediastinal masses who received their assigned chest radiation had a lower event rate than those who did not (p = 0.06). Patients whose cranial fields did or did not encompass the entire meningeal surface had equivalent CNS relapse rates.. Patients treated with LSA2L2 chemotherapy, a less than optimal regimen, benefited from cranial and mediastinal irradiation. Compliance with radiation volume guidelines was not essential for patients to receive the benefit of cranial irradiation.

Topics: Actuarial Analysis; Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Brain Neoplasms; Child; Combined Modality Therapy; Cyclophosphamide; Cytarabine; Daunorubicin; Doxorubicin; Humans; Infant; Leukocyte Count; Lymphoma; Mediastinal Neoplasms; Meningeal Neoplasms; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prednisone; Recurrence; Survival Rate; Thioguanine; Vincristine

Between 1 September 1981 and 31 December 1985, 382 previously untreated children with ALL were entered into study VII/81, a multicentric and randomized study with a modified BFM protocol. Patients were divided into three risk groups according to the initial lymphoblast count and liver and spleen enlargement: standard- (SR), medium- (MR), and high-risk (HR) groups. Of all patients, 94% attained complete remission. The actuarial probability of event-free survival is 0.62 +/- 0.04 (SR group, 0.66 +/- 0.06; HR group, 0.29 +/- 0.12). Sixty-one patients relapsed, 10 had isolated CNS relapses, and 11 CNS relapses were combined with bone marrow relapses. Concerning the duration of maintenance therapy, patients were randomized into two groups of 18 and 24 months respectively. Up to now, there has been a slight advantage for the 18-month group. Two different methods of CNS preventive therapy for SR patients (irradiation plus intrathecal methotrexate and intermediate-dose methotrexate (IDMTX) plus intrathecal methotrexate) were used and revealed a higher rate of CNS relapses but a lower rate of bone marrow relapses in the intermediate-dose MTX group.

Topics: Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Child; Clinical Trials as Topic; Combined Modality Therapy; Cyclophosphamide; Cytarabine; Doxorubicin; Germany, East; Humans; Leukemia, Lymphoid; Meningeal Neoplasms; Methotrexate; Prednisone; Random Allocation; Remission Induction; Risk; Thioguanine; Vincristine

From September 1976 to August 1979 the Pediatric Oncology Group accessed 145 children to study the effectiveness of modified LSA2-L2 therapy for the treatment of non-Hodgkin's lymphoma (NHL). Burkitt's lymphoma patients were ineligible; E-rosette-positive patients with greater than or equal to 25% blasts in the marrow entered after February 1977 were reported separately. Radiotherapy could be used to treat patients with compressive mediastinal disease at diagnosis and was prescribed for those with residual abdominal disease as demonstrated by second-look surgery on completion of induction chemotherapy. Confirmation of diagnosis by the Pathology Panel and Repository Center for Lymphoma Clinical Trials was mandatory. Diagnostic tissues of 131 patients were reviewed. Among 107 evaluable patients, 91 (85%) achieved complete remission. Differences in response rates among the three major histologic groups (lymphoblastic, undifferentiated, and large cell) were of statistical significance, with response being poorest for diffuse undifferentiated lymphoma (P = 0.03). Failure-free survival did not differ significantly for the three major histologic diagnoses. While response rate was lowest for Murphy Stage III patients (79%), the differences among the stages were not significant. Stage was not a significant prognostic factor for failure-free survival (P = 0.08). The number of patients still at risk and the Kaplan-Meier estimate of percentage of patients remaining at risk after 3 years is: Stage I, 8 (100%); Stage II, 10 (67%); Stage III, 28 (57%); Stage IV, 6 (39%); and greater than 25% blasts, 1 (13%). Stage III failure curves for lymphoblastic disease show continuing stepwise failure through 3 years. Among patients with diffuse large cell and undifferentiated disease, most failures occurred by 8 months. M1 and M2 levels of marrow involvement were not prognostic among children with lymphoblastic disease. The presence of a mediastinal mass was a significant factor contributing to failure in children with lymphoblastic disease without marrow involvement. Leucocytosis greater than 10,000/1, was a significant (P = less than 0.001) factor predicting failure-free survival for patients with large cell lymphoma. The delivery of radiotherapy was not a significant factor in achieving remission. No consistent benefit resulted from using radiotherapy to treat postinduction residual disease demonstrated on second-look exploration. The LSA2-L2 regimen was associated with consid

Topics: Adolescent; Antineoplastic Agents; Asparaginase; Bone Marrow; Carmustine; Child; Child, Preschool; Clinical Trials as Topic; Cyclophosphamide; Cytarabine; Daunorubicin; Female; Humans; Lymphoma; Lymphoma, Non-Hodgkin; Male; Mediastinal Neoplasms; Meningeal Neoplasms; Methotrexate; Neoplasm Staging; Prednisone; Prognosis; Radiotherapy Dosage; Thioguanine; Vincristine

One hundred patients were entered in a cooperative study comparing the efficacy of two different regimens in the induction treatment of acute nonlymphocytic leukemia (ANLL). Patients were randomly allocated to receive either the DAT or VAT combination; half of the patients were also randomized to receive CNS prophylaxis including intrathecal methotrexate + prednisone and cranial irradiation. Consolidation and maintenance therapy were uniform in responding patients. Out of 82 evaluable patients 41 (50%) attained complete remission (CR) with no significant difference between the two regimens. Median remission duration was slightly longer in the DAT group (32.5 vs 22 weeks); median survival was 34 weeks for all evaluable patients with no difference between the two schedules. Meningeal relapse occurred only in two patients after 19 and 99 weeks of continuous remission. Fourteen patients are still alive after 61 to greater than or equal to 155 weeks, of whom seven are in their initial remission (six in the DAT and one in the VAT group). We conclude that 1) DAT and VAT are equally effective in inducing CR in a high proportion of ANLL patients; 2) until marrow remission can be prolonged significantly, preventing CNS leukemia will not have any significant impact of the course of ANLL.

Topics: Adolescent; Adult; Antineoplastic Agents; Child; Child, Preschool; Cytarabine; Daunorubicin; Drug Therapy, Combination; Female; Humans; Leukemia; Leukemia, Erythroblastic, Acute; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Male; Meningeal Neoplasms; Methotrexate; Middle Aged; Prednisone; Remission, Spontaneous; Thioguanine; Time Factors; Vincristine

Topics: Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Combined Modality Therapy; Cyclophosphamide; Cytarabine; Daunorubicin; Doxorubicin; Etoposide; Exophthalmos; Humans; Infant; Leukemia, Megakaryoblastic, Acute; Male; Meningeal Neoplasms; Mitoxantrone; Orbital Neoplasms; Prednisone; Thioguanine; Vincristine

Topics: Antineoplastic Combined Chemotherapy Protocols; Child; Combined Modality Therapy; Cranial Irradiation; Cytarabine; Daunorubicin; Doxorubicin; Humans; Hydrocortisone; Leukemia, Monocytic, Acute; Male; Meningeal Neoplasms; Mercaptopurine; Methotrexate; Prednisone; Remission Induction; Testicular Neoplasms; Thioguanine

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

A case is reported of a 12-year-old boy with Di Guglielmo's syndrome who achieved complete remission for over three years before developing a central nervous system relapse. The poor results of treatment in this disease are reviewed and the arguments for routine central nervous system prophylaxis discussed.

Topics: Antineoplastic Agents; Child; Cytarabine; Daunorubicin; Drug Therapy, Combination; Humans; Leukemia, Erythroblastic, Acute; Male; Meningeal Neoplasms; Prednisolone; Thioguanine; Time Factors

Twenty-one children with acute nonlymphoblastic leukemia (ANLL) were treated with a combination regimen consisting of arabinosyl cytosine (Ara-C), 6-thioguanine (TG), and Adriamycin, The incidence of complete remission was 74%. For consolidation, addition courses of Ara-C and TG were given, followed by L-asparaginase. The maintenance program was the same as that for the lymphoblastic type (L-2) including intrathecal methotrexate for prophylaxis of meningeal leukemia. Of the 16 who were evaluable for the duration of complete remission, six developed bone marrow relapse, one meningeal leukemia within 3-14 months after entering complete remission and one was lost to follow-up. Eight remain in complete remission for 9-72 months. In five of eight, chemotherapy has been terminated after 3 years, and all continue in remission for 11-32 months post-treatment. Although the results do not compare well to those of the lymphoblastic morphology, long-term disease-free survival can be achieved with multiple-drug intensive treatment in childhood ANLL.

Topics: Acute Disease; Adolescent; Antineoplastic Agents; Asparaginase; Child; Child, Preschool; Cytarabine; Doxorubicin; Drug Therapy, Combination; Female; Humans; Infant; Leukemia; Male; Meningeal Neoplasms; Remission, Spontaneous; Thioguanine