Impact of measurable residual disease on outcomes of unrelated donor haematopoietic cell transplantation with post‐transplant cyclophosphamide in AML in first complete remission

Author:

Nagler Arnon1ORCID,Labopin Myriam2,Dholaria Bhagirathbhai3ORCID,Blaise Didier4,Bondarenko Sergey5,Vydra Jan6,Choi Goda7,Rovira Montserrat8,Reményi Péter9,Meijer Ellen10,Bulabois Claude Eric11,Diez‐Martin J. L.12,Yakoub‐Agha Ibrahim13,Brissot Eolia14ORCID,Spyridonidis Alexandros15ORCID,Sanz Jaime16,Patel Amit17,Arat Mutlu18,Bazarbachi Ali19,Bug Gesine20,Savani Bipin N.3,Giebel Sebastian21,Ciceri Fabio22ORCID,Mohty Mohamad2ORCID

Affiliation:

1. Division of Hematology Sheba Medical Center Tel Hashomer Israel

2. INSERM UMRs 938, Sevice d'hématologie Clinique et Thérapie Cellulaire, Hôpital Saint‐Antoine Sorbonne University Paris France

3. Vanderbilt University Medical Center Nashville Tennessee USA

4. Department of Hematology Institut Paoli Calmettes Marseille France

5. Raisa Gorbacheva Memorial Research Institute for Paediatric Oncology, Hematology First State Pavlov Medical University of St Petersburg St Petersburg Russian Federation

6. Servicio de Hematología Institute of Hematology and Blood Transfusion Prague Czech Republic

7. Department of Hematology University Medical Center Groningen, University of Groningen Groningen The Netherlands

8. Hematology Hospital Clinic, Institute of Hematology & Oncology Barcelona Spain

9. Haematology and Stem Cell Transplant Dél‐pesti Centrumkórház–Országos Hematológiai és Infektológiai Intézet Budapest Hungary

10. Department of Hematology Amsterdam UMC, Vrije Universiteit Amsterdam Amsterdam The Netherlands

11. Service d'Hématologie CHU Grenoble Alpes 38043 Grenoble France

12. Department of Hematology Hospital GU Gregorio Marañon, Instituto de Investigacion sanitaria Gregorio Marañon, Medicina, UCM Madrid Spain

13. CHU de Lille Univ Lille, INSERM U1286, Infinite Lille France

14. Hematology Hôpital Saint Antoine, Service d'Hématologie et Thérapie Cellulaire Paris France

15. Bone Marrow Transplantation Unit and Institute of Cell Therapy University of Patras Patras Greece

16. Hematology Department at University Hospital La Fe Instituto de Investigación Sanitaria La Fe Valencia Spain

17. Royal University Hospital Liverpool UK

18. Sisli Florence Nightingale Hospital Istanbul Turkey

19. Bone Marrow Transplantation Program, Department of Internal Medicine American University of Beirut Medical Center Beirut Lebanon

20. Department of Medicine 2, Hematology and Oncology Goethe University Frankfurt Frankfurt Germany

21. Bone Marrow Transplantation and Hematology‐Oncology Maria Sklodowska‐Curie National Research Institute of Oncology, Gliwice Branch Wybrzeze Armii Krajowej Gliwice Poland

22. Haematology and BMT Ospedale San Raffaele s.r.l Milan Italy

Abstract

SummaryPre‐transplant measurable residual disease (MRD) predicts relapse and outcome of allogeneic haematopoietic cell transplantation (allo‐HCT). The impact of MRD on the outcomes of post‐transplant cyclophosphamide (PTCy)‐based allo‐HCT from a matched unrelated donor (UD) is unknown. This study assessed the impact of MRD in acute myeloid leukaemia (AML) in the first complete remission (CR1). A total of 272 patients (MRD negative [MRD−], n = 165; MRD positive [MRD+], n = 107) with a median follow‐up of 19 (range: 16–24) months were studied. The incidence of grades II–IV and grades III–IV acute GVHD at day 180 was 25.2% and 25% (p = 0.99), and 10.6% and 6.8% (p = 0.29), respectively, and 2‐year chronic GVHD was 35% and 30.4% (p = 0.96) in MRD+ and MRD− cohorts, respectively. In multivariate analysis, MRD+ status was associated with a higher incidence of relapse (RI) (hazard ratio [HR] = 2.56, 95% CI: 1.39–4.72), lower leukaemia‐free survival (LFS) (HR = 2.04, 95% CI: 1.23–3.39), overall survival (OS) (HR = 1.83, 95% CI: 1.04–3.25) and GVHD‐free, relapse‐free survival (GRFS) (HR = 1.69, 95% CI: 1.10–2.58). MRD status did not have a significant impact on non‐relapse mortality (NRM), or acute or chronic GVHD risk. Among patients with AML undergoing UD allo‐HCT with PTCy, pre‐transplant MRD+ status predicted a higher relapse rate, lower LFS, OS and GRFS.

Publisher

Wiley

Subject

Hematology

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