Graft-Versus-Leukemia Effect of Allogeneic Stem-Cell Transplantation and Minimal Residual Disease in Patients With Acute Myeloid Leukemia in First Complete Remission

Author:

Versluis Jurjen1,Kalin Burak1,Zeijlemaker Wendelien1,Passweg Jakob1,Graux Carlos1,Manz Markus G.1,Vekemans Marie-Christiane1,Biemond Bart J.1,Legdeur Marie-Cecile J.C.1,Kooy Marinus van Marwijk1,de Weerdt Okke1,Wijermans Pierre W.1,Hoogendoorn Mels1,Bargetzi Mario J.1,Kuball Juergen1,Schouten Harry C.1,van der Velden Vincent H.J.1,Janssen Jeroen J.W.M.1,Pabst Thomas1,Lowenberg Bob1,Jongen-Lavrencic Mojca1,Schuurhuis Gerrit Jan1,Ossenkoppele Gert1,Cornelissen Jan J.1

Affiliation:

1. Jurjen Versluis, Burak Kalin, Bob Lowenberg, Mojca Jongen-Lavrencic, and Jan J. Cornelissen, Erasmus University Medical Center Cancer Institute; Vincent H.J. van der Velden, Erasmus University Medical Center, Rotterdam; Wendelien Zeijlemaker, Jeroen J.W.M. Janssen, Gerrit Jan Schuurhuis, and Gert Ossenkoppele, VU University Medical Center; Bart J. Biemond, Academic Medical Center, University of Amsterdam, Amsterdam; Marie-Cecile J.C. Legdeur, Medisch Spectrum Twente, Enschede; Marinus van Marwijk Kooy,...

Abstract

Purpose The detection of minimal residual disease (MRD) in patients with acute myeloid leukemia (AML) may improve future risk-adapted treatment strategies. We assessed whether MRD-positive and MRD-negative patients with AML benefit differently from the graft-versus-leukemia effect of allogeneic hematopoietic stem-cell transplantation (alloHSCT). Methods A total of 1,511 patients were treated in subsequent Dutch-Belgian Hemato-Oncology Cooperative Group and the Swiss Group for Clinical Cancer Research AML trials, of whom 547 obtained a first complete remission, received postremission treatment (PRT), and had available flow cytometric MRD before PRT. MRD positivity was defined as more than 0.1% cells with a leukemia-associated immunophenotype within the WBC compartment. PRT consisted of alloHSCT (n = 282), conventional PRT by a third cycle of chemotherapy (n = 160), or autologous hematopoietic stem-cell transplantation (n = 105). Results MRD was positive in 129 patients (24%) after induction chemotherapy before proceeding to PRT. Overall survival and relapse-free survival were significantly better in patients without MRD before PRT compared with MRD-positive patients (65% ± 2% v 50% ± 5% at 4 years; P = .002; and 58% ± 3% v 38% ± 4%; P < .001, respectively), which was mainly because of a lower cumulative incidence of relapse (32% ± 2% compared with 54% ± 4%; P < .001, respectively). Multivariable analysis with adjustment for covariables showed that the incidence of relapse was significantly reduced after alloHSCT compared with chemotherapy or autologous hematopoietic stem cell transplantation (hazard ratio [HR], 0.36; P < .001), which was similarly exerted in both MRD-negative and MRD-positive patients (HR, 0.38; P < .001; and HR, 0.35; P < .001, respectively). Conclusion The graft-versus-leukemia effect of alloHSCT is equally present in MRD-positive and MRD-negative patients, which advocates a personalized application of alloHSCT, taking into account the risk of relapse determined by AML risk group and MRD status, as well as the counterbalancing risk of nonrelapse mortality.

Publisher

American Society of Clinical Oncology (ASCO)

Subject

Cancer Research,Oncology

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