Intensified induction and consolidation with or without maintenance chemotherapy for acute myeloid leukemia (AML): two multicenter studies of the German AML Cooperative Group.

Abstract

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.

Comparison between four and eight cycles of intensive chemotherapy in adult acute myeloid leukemia: a randomized trial of the Finnish Leukemia Group

“…4,7,12,14,19,29,30 The disease-free survival and overall survival are also comparable with other recent studies 1,5,19,31,32 and they are clearly longer than those of our previous multicenter trial with less intensive postremission therapy. 8 In this protocol an attempt was made to select refractory patients early and give them alternative chemotherapy.…”

“…In at least two studies, however, maintenance treatment prolonged disease-free survival, 12,13 but benefit on overall survival was not seen in one of these studies. 13 In the study by Mandelli et al, 10 prolonged duration of moderately intensive consolidation treatment had no effect on disease-free survival or overall survival 10 but such treatment significantly increased disease-free survival in a report by Ohno et al 14 Several uncontrolled studies suggest that intensive postremission treatment is more effective than low-dose consolidation in prolonging remission.…”

Superiority of high-dose over intermediate-dose cytosine arabinoside in the treatment of patients with high-risk acute myeloid leukemia: results of an age-adjusted prospective randomized comparison

“…Patients of all ages who achieved a complete remission subsequently received TAD-9 for consolidation and monthly maintenance therapy for 3 years. 17,18 Patients with antecedent hematologic disorders, secondary leukemias, and a preceding autologous or allogeneic bone marrow transplantation were excluded from the study. Further exclusion criteria comprised coronary heart disease, heart failure, cardiomyopathy, severe arterial hypertension, abnormal liver function tests (aspartate aminotransferase (AST), alanine aminotransferase (ALT), or alkaline phosphatase (AP) more than three times the upper normal limits, total bilirubin Ͼ2.0 mg/dl), impaired renal function (serum creatinine Ͼ2.0 mg/dl), severe infections or pregnancy.…”

Cytogenetic subgroups in acute myeloid leukemia differ in proliferative activity and response to GM-CSF

“…Eligible patients underwent the TAD-9 regimen as first induction cycle. 51 TAD-9 comprized 100 mg/m 2 /day araC given by contious i.v. infusion on days 1 and 2 followed by short-term infusions of araC 100 mg/m 2 every 12 h on days 3-8; 6-thioguanine 100 mg/m 2 every 12 h orally on days 3-9 and 60-min infusions of daunorubicin 60 mg/m 2 /day on days 3-5.…”