Treatment results of children and adolescents with relapsed AML who were initially treated according to the AML-MM-2006 protocol

Abstract

Introduction. Relapse of acute myeloid leukemia (AML) develops in children who received intensive chemotherapy and achieved the first complete remission (CR1). Only intensive anti-relapse chemotherapy followed by allogeneic hematopoietic cell transplantation (allo-HSCT) may lead to cure.Aim — to present the results of treatment of children with AML who relapsed after completion of treatment or while on therapy according to the AML-MM-2006 protocol.Materials and methods. The study included children with AML who relapsed after completion of treatment of the first-line therapy according to the AML-MM-2006 protocol. During the follow-up period (median — 4.6 years), 68 relapses were registered among 187 patients who reached CR1 (early — 36, late — 26; with a change of phenotype to ALL-6). The cumulative probability of relapse was 40 %. Four (6 %) patients with relapsed AML initially belonged to the group of standard, 33 (54 %) — of intermediate risk of relapse of AML and 25 (40 %) — to the group of high risk. Eleven (18 %) were patients with “CBF-leukemia”, 19 (31 %) — with rearrangements of the 11q23 (KMT2A gene). Fludarabine, high doses of cytarabine and idarubicin in 33 (80 %) or mitoxantrone in 8 (20 %) patients were used to induce the second complete remission (CR2) in 41 patients (66 %).Results. Out of 53 patients who received chemotherapy as a second induction therapy, CR2 was achieved in 30 patients (57 %) (in 9 — with early, in 21 — with late relapse) after chemotherapy courses; 2 patients died within 30 days of the start of CT; 21 patients were refractory to chemotherapy. HSCT after relapse was performed in 51 patients, mainly from a haploidentical donor. Twenty-five patients underwent HSCT in CR2, 26 — in the status of “active disease”. Among patients transplanted into CR2, the probability of relapse was 20 %, and the overall survival rate was 80 %. Among patients transplanted outside of CR2, the probability of achieving CR2 was 77 %, the probability of relapse was 50 % and overall survival (OS) 58 %. The probability of OS in the group as a whole reached 52 %. The most significant prognostic factors of an unfavorable outcome were early relapse, refractory course of relapse, M7 variant of AML, complex karyotype and rearrangements of the ETV6 gene, combined (“bone marrow + CNS damage + non-hematopoietic tissue”) relapse and relapse after HSCT performed in CR1.Conclusion. About 50 % of patients with relapses of AML can be cured with the help of high-dose chemotherapy and allo-HSCT.