Risk-adapted postremission therapy in acute myeloid leukemia: results of the german multicenter AML HD93 treatment trial

Abstract

The objective of the AML HD93 treatment trial was to evaluate the outcome in young adults with acute myeloid leukemia (AML) after postremission therapy was stratified according to cytogenetically defined risk. The rationales for the study design were based (i) on previous favorable results with high-dose cytarabine in AML with t(8;21), inv/t(16q22) and in AML with normal karyotype, and ii) on encouraging results obtained in several phase II trials using autologous stem cell transplantation (SCT). Between July 1993 and January 1998, 223 eligible patients, 16-60 years of age with newly diagnosed AML other than French-American-British type M3/M3v, were entered into the trial. Risk groups were defined as follows: low risk: t(8;21) or inv/t(16q22); intermediate risk: normal karyotype; high risk: all other chromosomal abnormalities. Following intensive double induction therapy with idarubicin, cytarabine and etoposide, all patients in complete remission (CR) received a first consolidation therapy with high-dose cytarabine and mitoxantrone (HAM). A second consolidation therapy was stratified according to the risk group: low risk: HAM; intermediate risk: related allogeneic SCT or sequential HAM; high risk: related allogeneic or autologous SCT. Double induction therapy resulted in a high CR rate of 74.5%, and 90% of the responding patients were eligible for consolidation therapy. Survival for all 223 trial entrants was 40%, and for the 166 patients who entered CR, disease-free (DFS) and overall survival were 40 and 51% after 5 years, respectively. Within the low-, intermediate-and high-risk groups, DFS and survival after 5 years were 62.5 and 87, 40 and 49 and 17 and 26% respectively, without advantage for allogeneic transplantation in the intermediate-and high-risk groups. Postremission therapy-related mortality was 0, 7 and 14%, respectively. This study demonstrates the feasibility of cytogenetically defined risk-adapted consolidation therapy. The overall trial results are at least equivalent to those of published trials supporting the risk-adapted treatment strategy.

CEBPα mutations in childhood acute myeloid leukemia

“…28 The cytogenetically defined risk classification of AML may also have an impact in designing a treatment trial in AML by risk-adapted postremission therapy. 29 In the present series, by using various molecular technology in addition to conventional cytogenetic analysis, we identified that 47.9% (56/ 117) of patients had the four major recurrent genetic abnormalities of AML1-ETO, CBFb-MYH11, PML-RARa and MLL rearrangements defined by the WHO classification. 15 However, approximately half of children with AML have no chromosomal or genetic abnormalities that can predict outcome, efforts have been made to improve the prognostic stratification on this group of patients.…”

Old and new prognostic factors in acute myeloid leukemia with deranged core‐binding factor beta

“…Prognostic factors of relapse risk in CBFb-AML subset are still a matter of debate. Female gender, older age, and low-platelet count have been reported as predictors for inferior outcome and/or shorter disease-free survival in patients enrolled in prospective trials [1,17,18]. Furthermore, higher white blood cells (WBCs) and low-platelet counts have been identified as bad predictor factors for CR achievements [19,20].…”

The role of allogeneic transplantation in high-risk acute myelogenous leukemia

“…Fourthly, all of the clinical trials have been characterized by lack of compliance with the assigned treatment. 13 As shown in Table 2, only 70% of patients in four of the large studies actually received an HLAidentical sibling transplant. Moreover, less than 50% of patients available for randomization to autologous BMT or conventional chemotherapy were randomized and less than 70% of patients assigned to receive autografts actually received them.…”