In two multicenter trials, a total of 576 patients with acute myeloid leukemia (AML) were treated and found to be evaluable. Two hundred forty-two patients were in a 1978 pilot study and 334 patients were in a 1982 randomized study. Ages were between 15 and 78 years (median, 48). The uniform remission induction therapy in both studies consisted of one to two courses of a 9-day combination of 6-thioguanine (TG) with cytosine arabinoside (ARA-C) and daunorubicin (DNR) [TAD9]. The timing and sequencing of TAD9 was designed according to cell kinetic effects of ARA-C. A complete remission (CR) was achieved in 65% (70% and 61%, respectively) of patients within a median of 33 days, and in 68% of responders after only one course. The CR rate in patients 60 to 78 years of age was 51% (66% and 39%, respectively). In the 1978 pilot study, different protocols of post-remission treatment were applied at the different centers: monthly 5-day maintenance, TAD9 consolidation, both consolidation and maintenance, or no further therapy. The group receiving treatment during CR showed 24% probability of remissions at 4 years v 0% probability of remissions in the untreated group. Between the different post-remission protocols, no significant differences were observed. Remission duration was not influenced by age, WBC, or morphologic cell type, but was longer in patients achieving CR within 30 days (P = .017). In the subsequent 1982 study, 145 patients in CR were randomized for TAD9 consolidation with or without monthly maintenance. The updated life-table analysis revealed a predicted rate of continuous remission at 2 1/2 years of 30% for the maintenance and 17% for the nonmaintenance arm (P = .003). These results of response and remission duration in adult patients of all ages support the validity of intensified induction therapy and of consequent myelosuppressive treatment in remission.
No statistically significant differences in treatment efficacy were detected between 20 Gy IF radiotherapy and 1X (COPP + ABVD) chemotherapy following CR after six cycles of alternating chemotherapy in patients with advanced-stage HD. However, limited observations in a non-randomized cohort indicate that patients without consolidation treatment of CR after 6 cycles of chemotherapy may have an elevated risk of relapse.
One hundred seventy adult patients with acute lymphoblastic leukemia (ALL) or acute undifferentiated leukemia (AUL) were entered into a prospective multicenter therapy trial at 25 hospitals. The aim of the trial was to improve remission duration by using a modified form of an intensified induction regimen that was successful in childhood ALL, to define immunologic subtypes of ALL by use of cell-surface markers, and to extract other possible prognostic factors. The overall complete remission rate was 77.8%. The median overall survival time was 26 months, being 4 months for nonresponders and 32 months for responders. The median remission duration for the 126 patients with complete remission was 20 months. Prognostically favorable factors for remission duration were response to chemotherapy within 4 weeks, age less than 35 years, a low initial leukocyte count, and the immunologic subtypes c- ALL with early response to therapy and T-ALL, where 61% and 58%, respectively, are still in complete remission at 3 years. An adverse influence on remission duration was observed for the subtype null-ALL, with a median survival of 13 months, and for patients with a delayed response to induction therapy, independent of phenotype.
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