TY - JOUR
T1 - Graft-Versus-Leukemia effect of allogeneic stem-cell transplantation and minimal residual disease in patients with acute myeloid leukemia in first complete remission
AU - Versluis, Jurjen
AU - Kalin, Burak
AU - Zeijlemaker, Wendelien
AU - Passweg, Jakob
AU - Graux, Carlos
AU - Manz, Markus G.
AU - Vekemans, Marie Christiane
AU - Biemond, Bart J.
AU - Legdeur, Marie Cecile J.C.
AU - Kooy, Marinus van Marwijk
AU - de Weerdt, Okke
AU - Wijermans, Pierre W.
AU - Hoogendoorn, Mels
AU - Bargetzi, Mario J.
AU - Kuball, Juergen
AU - Schouten, Harry C.
AU - van der Velden, Vincent H.J.
AU - Janssen, Jeroen J.W.M.
AU - Pabst, Thomas
AU - Lowenberg, Bob
AU - Jongen-Lavrencic, Mojca
AU - Schuurhuis, Gerrit Jan
AU - Ossenkoppele, Gert
AU - Cornelissen, Jan J.
PY - 2017/1/1
Y1 - 2017/1/1
N2 - 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-versusleukemia effect of allogeneic hematopoietic stem-cell transplantation (alloHSCT). MethodsAtotal of 1,511 patients were treated in subsequent Dutch-Belgian Hemato-Oncology Cooperative Group and the Swiss Group for Clinical Cancer ResearchAMLtrials, 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), conventionalPRTby 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 withoutMRDbefore PRT compared with MRD-positive patients (65% 6 2% v 50% 6 5% at 4 years; P = .002; and58%63%v38%64%; P < .001, respectively), which was mainly because of a lower cumulative incidence of relapse (32% 6 2% compared with 54% 6 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.
AB - 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-versusleukemia effect of allogeneic hematopoietic stem-cell transplantation (alloHSCT). MethodsAtotal of 1,511 patients were treated in subsequent Dutch-Belgian Hemato-Oncology Cooperative Group and the Swiss Group for Clinical Cancer ResearchAMLtrials, 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), conventionalPRTby 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 withoutMRDbefore PRT compared with MRD-positive patients (65% 6 2% v 50% 6 5% at 4 years; P = .002; and58%63%v38%64%; P < .001, respectively), which was mainly because of a lower cumulative incidence of relapse (32% 6 2% compared with 54% 6 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.
UR - http://www.scopus.com/inward/record.url?scp=85047193816&partnerID=8YFLogxK
U2 - 10.1200/PO.17.00078
DO - 10.1200/PO.17.00078
M3 - Article
AN - SCOPUS:85047193816
VL - 1
SP - 1
EP - 13
JO - JCO Precision Oncology
JF - JCO Precision Oncology
IS - 1
ER -