Long-term results of treatment of patients with acute myeloid leukemia according to the protocol of the Russian multicenter randomized trial of AML-10

The tasks of the Russian multicenter randomized trial of AML-10 were to evaluate of the efficacy of 2 consolidation courses – either (1st branch) with standard dose Cytarabine (7 + 3), or (2nd branch) – at the high dose (HiDAC 1 g/m2, twice a day, 1–3 days) in combination with Idarubicin (8 mg/m2, 3 days) and mitoxantrone (10 mg/m2, 3 days); after administration of 2 courses of induction 7 + 3 with Daunorubicin in a dose of 60 mg/m2 on the introduction and subsequent maintenance therapy by 6 courses 5 + 5 (Cytarabine +6MP).
Material and methods. From January 2010 to January 2013 250 AML patients were included in the trial from 20 Hematological Centers of theRussian Federation. 125 of 250 patients (73 women and 52 men) aged 17 to 59 years (mean age: 45 years) were randomized to the 1st branch of therapy and 125 patients (69 women and 56 men) aged between 16 and 60 years (mean age: 43 years) – to the 2nd branch. 212 patients were included in the analysis carried out in September 2015 (there is no data about 39 patients). Cytogenetic data are presented in 75% of patients: in the 1st branch 17.3% of cases were referred to favorable group on cytogenetics, 66.7% cases – to the intermediate risk, and 16% cases – to the negative risk; 2nd branch – 20; 53.6 and 21.4% respectively.

Results. Achievement of complete remission (CR) was observed in 153 (72.2%) of patients, the resistance was in 28 (13.2%), death occurred during induction in 31 (14.6%), death in complete remission – in 22 (14.4%). Five year overall survival rate (OS) was 30.7%, disease-free survival (DFS) rate was 32.7%. There was no difference in OS and DFS in patients in the 1st and 2nd branch of treatment: 31.6 and 29.8%; 39.6 and 25.8% respectively. Upon achievement of CR after the 1 cours DFS in the 1st branch was in 44%, in the 2nd branch – 31%. After the 2nd course – 34 and 20%. In multivariate analysis (MA, Cox model), including gender, age, randomization option, initial leukocytosis and platelet count, the percentage of blast cells in the peripheral blood and bone marrow, risk for cytogenetics, albumin and LDH, achievement of CR after the 1st or 2nd course, the performance of allogeneic HSCT in the 1st CR, there were identified factors statistically significantly negative affected on the indices of 5-year OS and DFS: unfavorable cytogenetic group (HR 1.9; p = 0.014 and HR 3.047; p = 0.0049, respectively), achievement of CR after the 2nd course (HR 2.4; p = 0.003 and HR 2.3; p = 0.007) and the non-performance of allogeneic HSCT in the 1st CR (HR 4.71; p = 0.001 and HR 4.9; p = 0.006).
Conclusion. Consolidation HiDAC has no advantage over consolidation with standard doses Cytarabine in using a high cumulative dose of anthracyclines. High-dose consolidation does not improve long-term survival results in patients from the various risk groups: in the achievement of CR after the 2nd course and from the intermediate /unfavorable risk group for cytogenetics. Upon reaching the CR after the 2nd course of chemotherapy just the performance of allogeneic HSCT allows you to get long-term results that are comparable with those in groups of favorable prognosis.

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