The European LeukemiaNet AML Working Party consensus statement on allogeneic HSCT for patients with AML in remission: an integrated-risk adapted approach

Abstract

Allogeneic hematopoietic stem cell transplantation (alloHSCT) is frequently applied as part of treatment in acute myeloid leukemia (AML) in first or subsequent remission. It reduces relapse, but non-relapse mortality (NRM) and morbidity may counterbalance that beneficial effect. Here we review recent studies reporting new disease specific prognostic markers as well as alloHSCT related risk factors to be identified at specific time points during treatment. We propose risk assessment as a dynamic process during treatment, incorporating both disease and transplant related factors for the decision to proceed either to alloHSCT or with a non transplant strategy, whereby alloHSCT may be favored if projected disease free survival can be expected to be improved by at least 10%, based on individual risk assessment. Pivotal for such an approach are initial disease risk assessment, search for a sibling or unrelated donor early after diagnosis, and the incorporation of time dependent risk factors, all within the context of an integrated therapeutic management approach.4

Characteristics Predicting Outcomes of Allogeneic Stem-Cell Transplantation in Relapsed Acute Myelogenous Leukemia

“…A graft-versus-leukemia effect gives ahsct superior anti-leukemic activity, with a greater chance of maintaining remission than is achieved with consolidation chemotherapy 8,9 . However, its benefit is limited by greater treatment-related mortality, which can be as high as 20%-30%, and the morbidity and mortality associated with graft-versus-host disease (gvhd) 6,8,[10][11][12] .…”

Intesive fludarabine-high dose cytarabine-idarubicin combination as induction therapy with risk-adapted consolidation may improve treatment efficacy in younger Acute Myeloid Leukemia (AML) patients: Rationales, evidences and future perspectives

“…risk assessment according to clinical and biological features at diagnosis and response to induction) and patientrelated factors (i.e. performance status, comorbidities, infectious complications) (1,7,20) and the correct identification of patients who may benefit from early allo-SCT consolidation is fundamental in order to maximize treatment efficacy (21).…”

Acute myeloid leukemia: 2016 Update on risk‐stratification and management

“…Cases in which a smaller proportion of alleles are affected "low allelic ratio" (AR) are usually thought to have a lower risk of relapse than patients with high AR, but this has been debated [16]. In general, the risk of relapse has been considered sufficiently high to justify allogeneic hematopoietic cell transplant (allo HCT) in the adverse and int-2 groups (relapse rates within 1-2 years without allo HCT >90% and 70-80% respectively (with FLT3 ITD1, considered as int-2), and probably in the int-1 group (relapse rate without allo HCT 50-60%), but not in the favorable group (relapse rate without HCT 30-40%) [17]. As discussed below, the decision to proceed to allo HCT also depends on the risk of post-HCT nonrelapse mortality.…”

“…Although the most obvious of these is TRM within the first 100 days of allo HCT, patients who are cured of their leukemia still have a 30% reduction in life expectancy [94] consequent to chronic graft vs. host disease (GVHD) and development of secondary malignancies, which occur at a much higher rate than after chemotherapy without allo HCT [95]. While the late effects are difficult to forecast, a "Hematopoietic Cell Transplantation Co-Morbidity Index" (HCT-CI) has been shown predictive of early post-HCT death, as has a European Group for Blood and Marrow Transplantation (EBMT) index [17,93]. Table V adapted from a EBMT review [17] provides approximations of benefit (reduction in relapse) and risk (early "nonrelapse mortality," NRM) associated with allo HCT in CR1.…”

“…The decision to perform allo HCT in CR1 derives from the expectation that the reduction in risk of relapse provided by HCT is greater than the risk of allo HCT-related complications [17,93]. Although the most obvious of these is TRM within the first 100 days of allo HCT, patients who are cured of their leukemia still have a 30% reduction in life expectancy [94] consequent to chronic graft vs. host disease (GVHD) and development of secondary malignancies, which occur at a much higher rate than after chemotherapy without allo HCT [95].…”