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

J. Versluis; B. Kalin; W. Zeijlemaker; J. Passweg; C. Graux; M.G. Manz; M.C. Vekemans; B.J. Biemond; M.C.J.C. Legdeur; M.V. Kooy; O. de Weerdt; P.W. Wijermans; M. Hoogendoorn; M.J. Bargetzi; J. Kuball; H.C. Schouten; V.H.J. van der Velden; J.J.W.M. Janssen; T. Pabst; B. Lowenberg; M. Jongen-Lavrencic; G.J. Schuurhuis; G. Ossenkoppele; J.J. Cornelissen

doi:10.1200/PO.17.00078

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

J. Versluis, B. Kalin, W. Zeijlemaker, J. Passweg, C. Graux, M.G. Manz, M.C. Vekemans, B.J. Biemond, M.C.J.C. Legdeur, M.V. Kooy, O. de Weerdt, P.W. Wijermans, M. Hoogendoorn, M.J. Bargetzi, J. Kuball, H.C. Schouten, V.H.J. van der Velden, J.J.W.M. Janssen, T. Pabst, B. LowenbergM. Jongen-Lavrencic, G.J. Schuurhuis, G. Ossenkoppele, J.J. Cornelissen^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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% v38% 64%; 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. (C) 2017 by American Society of Clinical Oncology

Original language	English
Number of pages	13
Journal	JCO Precision Oncology
Volume	1
Issue number	1
DOIs	https://doi.org/10.1200/PO.17.00078
Publication status	Published - 2017

Keywords

RISK-ASSESSMENT
FLOW-CYTOMETRY
COMORBIDITY INDEX
REDUCED-INTENSITY
PROGNOSTIC IMPACT
AML
ADULTS
BLOOD
TIME
RECOMMENDATIONS

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10.1200/PO.17.00078

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Versluis, J., Kalin, B., Zeijlemaker, W., Passweg, J., Graux, C., Manz, M. G., Vekemans, M. C., Biemond, B. J., Legdeur, M. C. J. C., Kooy, M. V., de Weerdt, O., Wijermans, P. W., Hoogendoorn, M., Bargetzi, M. J., Kuball, J., Schouten, H. C., van der Velden, V. H. J., Janssen, J. J. W. M., Pabst, T., ... Cornelissen, J. J. (2017). Graft-Versus-Leukemia Effect of Allogeneic Stem-Cell Transplantation and Minimal Residual Disease in Patients With Acute Myeloid Leukemia in First Complete Remission. JCO Precision Oncology, 1(1). https://doi.org/10.1200/PO.17.00078

@article{369a6abf3ba74c54add2fde33ad0d96f,

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

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% v38% 64%; 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. (C) 2017 by American Society of Clinical Oncology",

keywords = "RISK-ASSESSMENT, FLOW-CYTOMETRY, COMORBIDITY INDEX, REDUCED-INTENSITY, PROGNOSTIC IMPACT, AML, ADULTS, BLOOD, TIME, RECOMMENDATIONS",

author = "J. Versluis and B. Kalin and W. Zeijlemaker and J. Passweg and C. Graux and M.G. Manz and M.C. Vekemans and B.J. Biemond and M.C.J.C. Legdeur and M.V. Kooy and {de Weerdt}, O. and P.W. Wijermans and M. Hoogendoorn and M.J. Bargetzi and J. Kuball and H.C. Schouten and {van der Velden}, V.H.J. and J.J.W.M. Janssen and T. Pabst and B. Lowenberg and M. Jongen-Lavrencic and G.J. Schuurhuis and G. Ossenkoppele and J.J. Cornelissen",

year = "2017",

doi = "10.1200/PO.17.00078",

language = "English",

volume = "1",

journal = "JCO Precision Oncology",

issn = "2473-4284",

publisher = "American Society of Clinical Oncology",

number = "1",

}

Versluis, J, Kalin, B, Zeijlemaker, W, Passweg, J, Graux, C, Manz, MG, Vekemans, MC, Biemond, BJ, Legdeur, MCJC, Kooy, MV, de Weerdt, O, Wijermans, PW, Hoogendoorn, M, Bargetzi, MJ, Kuball, J, Schouten, HC, van der Velden, VHJ, Janssen, JJWM, Pabst, T, Lowenberg, B, Jongen-Lavrencic, M, Schuurhuis, GJ, Ossenkoppele, G & Cornelissen, JJ 2017, 'Graft-Versus-Leukemia Effect of Allogeneic Stem-Cell Transplantation and Minimal Residual Disease in Patients With Acute Myeloid Leukemia in First Complete Remission', JCO Precision Oncology, vol. 1, no. 1. https://doi.org/10.1200/PO.17.00078

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, J.

AU - Kalin, B.

AU - Zeijlemaker, W.

AU - Passweg, J.

AU - Graux, C.

AU - Manz, M.G.

AU - Vekemans, M.C.

AU - Biemond, B.J.

AU - Legdeur, M.C.J.C.

AU - Kooy, M.V.

AU - de Weerdt, O.

AU - Wijermans, P.W.

AU - Hoogendoorn, M.

AU - Bargetzi, M.J.

AU - Kuball, J.

AU - Schouten, H.C.

AU - van der Velden, V.H.J.

AU - Janssen, J.J.W.M.

AU - Pabst, T.

AU - Lowenberg, B.

AU - Jongen-Lavrencic, M.

AU - Schuurhuis, G.J.

AU - Ossenkoppele, G.

AU - Cornelissen, J.J.

PY - 2017

Y1 - 2017

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-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% v38% 64%; 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. (C) 2017 by American Society of Clinical Oncology

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-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% v38% 64%; 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. (C) 2017 by American Society of Clinical Oncology

KW - RISK-ASSESSMENT

KW - FLOW-CYTOMETRY

KW - COMORBIDITY INDEX

KW - REDUCED-INTENSITY

KW - PROGNOSTIC IMPACT

KW - AML

KW - ADULTS

KW - BLOOD

KW - TIME

KW - RECOMMENDATIONS

U2 - 10.1200/PO.17.00078

DO - 10.1200/PO.17.00078

M3 - Article

SN - 2473-4284

VL - 1

JO - JCO Precision Oncology

JF - JCO Precision Oncology

IS - 1

ER -

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

Abstract

Keywords

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