GRAFT VERSUS LEUKEMIA EFFECT OF ALLOGENEIC STEM CELL TRANSPLANTATION AND MINIMAL RESIDUAL DISEASE IN PATIENTS WITH AML IN FIRST COMPLETE REMISSION.
Author(s): ,
Jurjen Versluis
Affiliations:
Erasmus Medical Center Cancer Institute,Rotterdam,Netherlands
,
Burak Kalin
Affiliations:
Erasmus Medical Center Cancer Institute,Rotterdam,Netherlands
,
Wendelien Zeijlemaker
Affiliations:
VU University Medical Center,Amsterdam,Netherlands
,
Jakob Passweg
Affiliations:
University Hospital Basel,Basel,Switzerland
,
Carlos Graux
Affiliations:
Mont-Godinne,Yvoir,Belgium
,
Markus Manz
Affiliations:
University Hospital Zürich,Zürich,Switzerland
,
Marie-Christiane Vekemans
Affiliations:
Cliniques universitaires Saint-Luc, UCL,Brussels,Belgium
,
Bart Biemond
Affiliations:
Academic Medical Center, University of Amsterdam,Amsterdam,Netherlands
,
Marie-Cecile Legdeur
Affiliations:
Medisch Spectrum Twente,Enschede,Netherlands
,
Marinus van Marwijk Kooy
Affiliations:
Isala Hospital,Zwolle,Netherlands
,
Jeroen Janssen
Affiliations:
VU University Medical Center,Amsterdam,Netherlands
,
Thomas Pabst
Affiliations:
Inselspital, Bern University Hospital,Bern,Switzerland
,
Bob Lowenberg
Affiliations:
Erasmus Medical Center Cancer Institute,Rotterdam,Netherlands
,
Mojca Jongen-Lavrencic
Affiliations:
Erasmus Medical Center Cancer Institute,Rotterdam,Netherlands
,
Gerrit Jan Schuurhuis
Affiliations:
VU University Medical Center,Amsterdam,Netherlands
,
Gert Ossenkoppele
Affiliations:
VU University Medical Center,Amsterdam,Netherlands
Jan Cornelissen
Affiliations:
Erasmus Medical Center Cancer Institute,Rotterdam,Netherlands
EHA Library. Versluis J. Jun 23, 2017; 181399; S112
Jurjen Versluis
Jurjen Versluis
Contributions
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Abstract

Abstract: S112

Type: Oral Presentation

Presentation during EHA22: On Friday, June 23, 2017 from 12:00 - 12:15

Location: Hall C

Background
The detection of minimal residual disease (MRD) in patients with acute myeloid leukemia (AML) may improve future risk-adapted strategies of AML treatment. The presence of MRD after induction treatment has firmly been shown to predict for relapse and overall outcome, irrespective of type of post-remission treatment (PRT). Currently it is unknown whether and how the presence or absence of MRD should guide the application of allogeneic hematopoietic stem cell transplantation (alloHSCT) as PRT.

Aims

We addressed whether and to what extent alloHSCT quantitatively reduces relapse as compared to conventional post-remission treatment (PRT) in upfront treated patients with MRD positive or MRD negative AML in first hematological complete remission (CR1).

Methods
A total of 1,511 patients were treated in subsequent HOVON-SAKK AML trials of whom 547 patients obtained a CR1, received PRT and had available flow cytometric MRD prior to PRT. MRD positivity was defined by more than 0.1% cells with a leukemia associated phenotype within the white blood cell compartment. MRD status was not known by clinicians during AML treatment. PRT consisted of alloHSCT (n=282), or conventional PRT by a third cycle of chemotherapy (n=160) or autologous HSCT (n=105). Endpoints of the study included overall survival (OS), relapse-free survival (RFS), and cumulative incidences of relapse and non-relapse mortality (NRM) at 4 years. A time-dependent analysis was performed by applying multivariable Cox regression with time-dependent covariate alloHSCT with the cumulative incidence of relapse as primary endpoint.

Results

MRD was positive in 129 (24%) patients after induction chemotherapy before proceeding to PRT. The latest European LeukemiaNET risk classification was similarly distributed among MRD negative and MRD positive patients. No differences were present in transplant characteristics in MRD positive and MRD negative patients.
OS and RFS was significantly better in patients without MRD prior to PRT as compared to MRD positive patients (65±2% compared to 50±5% at 4 years, p=0.002, and 58±3% compared to 38±4%, p<0.001, respectively). Improved outcome was mainly caused by a lower cumulative incidence of relapse in MRD negative patients as compared to MRD positive patients (32±2% compared to 54±4% at 4 years, p<0.001, respectively), while NRM was not significantly different and estimated 10±1%. NRM split by EBMT risk score showed less NRM in patients with a low EBMT-risk score as compared to patients with a high EBMT risk score (<2 compared to >2, 10±2% compared to 22±4%, p=0.005, respectively).
Multivariable analysis with adjustment for covariates showed that the incidence of relapse was significantly reduced following alloHSCT as compared to chemotherapy or autologous HSCT (HR 0.36, p<0.001), which was similarly exerted in MRD negative and positive patients (HR 0.38, p<0.001 and HR 0.35, p<0.001). RFS was also improved following alloHSCT as compared to chemotherapy or autoHSCT (HR 0.53, p<0.001), while no significant differences were found for OS.

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 the risk of relapse determined by AML risk group and MRD status as well as the counterbalancing risk of NRM into account.

Session topic: 4. Acute myeloid leukemia - Clinical

Keyword(s): Minimal residual disease (MRD), Graft-versus-leukemia, Allogeneic hematopoietic stem cell transplant, Acute Myeloid Leukemia

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