Adult AML patients can be stratified into good-risk, intermediate risk, and poor-risk groups based on the disease characteristics including numeric and/or structural chromosomal abnormalities and the presence of specific mutations that can also direct choice of curative post-remission therapy, especially for patients less than 60 years of age. For instance, current European LeukemiaNet (ELN) consensus incorporates molecular mutations to derive AML prognostic risk groups (Table 1). In current thinking, allogeneic HSCT is generally recommended when the relapse incidence with non-transplant approaches is expected to be above 35% to 40%.
Table1. European LeukemiaNet Acute Myeloid Leukemia Risk Classification 2017
Numerous groups have evaluated prospectively the relative benefits of allogeneic HSCT versus non-allogeneic therapies (consolidation chemotherapy or autologous HSCT) in adult AML patients 18 to 60 years of age in CR1. Treatment allocation was by biologic assignment as a surrogate for true randomization, with allogeneic HSCT for patients with available human leukocyte antigen (HLA)–matched sibling donors (donor group) and non-allogeneic consolidation for those lacking matched sibling donors (no-donor group). Some studies further stratified post-remission outcomes by cytogenetic risk. Individual studies, when analyzed on an intent-to-treat (ITT) donor versus no-donor basis, typically demonstrated that allogeneic HSCT was effective at improving disease-free survival, but overall survival benefit was hard to document because of graft-versus-host disease (GVHD) and other treatment-related mortality. Moreover, trans plantation in CR2 salvages some of the patients who relapsed, thus making overall survival similar with the two approaches.
A meta-analysis of over 6000 patients in 24 biologic treatment assignment trials, however, confirmed that overall survival was in fact better in allogeneic matched related donor transplantation in AML-CR1, with a hazard ratio (HR) of death at 0.90 (95% confidence interval [CI], 0.82 to 0.97). Importantly, when stratified by cytogenetic risk, there was an overall survival benefit of allogeneic transplantation (Table 2) for both intermediate-risk (HR, 0.83; 95% CI, 0.74 to 0.93) and poor-risk (HR, 0.73; 95% CI, 0.59 to 0.90) cytogenetic groups, but not for good-risk AML-CR1 (HR, 1.07; 95% CI, 0.83 to 1.38) (Fig. 1). These findings were particularly relevant for patients with normal cytogenetic AML, who constitute the largest subgroup and for whom no consensus regarding optimal post-remission treatment was previously available. These studies however did not have the benefit of prognostic assignment based on FLT3, NPM1, or other molecular markers.
Table2. Allogeneic Transplantation Guidelines for Adult Acute Myeloid Leukemia Based on Commonly Assessed Cytogenetic and Molecular Markers
Fig1. META-ANALYSIS OF OVERALL SURVIVAL BENEFIT IN FIRST COMPLETE REMISSION OF ACUTE MYELOID LEUKEMIA FOR YOUNGER ADULTS. AML, Acute myeloid leukemia; CI, confidence interval; HR, hazard ratio. (Redrawn from Koreth J, Schlenk R, Kopecky KJ, et al. Allogeneic stem cell transplantation for acute myeloid leukemia in first complete remission: systematic review and meta-analysis of prospective clinical trials. JAMA. 2009;301:2349.) Sources cited within Fig. 1 can be found following the reference list online at Elsevier eBooks for Practicing Clinicians.
