Impact of measurable residual disease on outcomes of unrelated donor haematopoietic cell transplantation with post-transplant cyclophosphamide in AML in first complete remission |
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| Authors: | Arnon Nagler Myriam Labopin Bhagirathbhai Dholaria Didier Blaise Sergey Bondarenko Jan Vydra Goda Choi Montserrat Rovira Péter Reményi Ellen Meijer Claude Eric Bulabois J L Diez-Martin Ibrahim Yakoub-Agha Eolia Brissot Alexandros Spyridonidis Jaime Sanz Amit Patel Mutlu Arat Ali Bazarbachi Gesine Bug Bipin N Savani Sebastian Giebel Fabio Ciceri Mohamad Mohty |
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| Institution: | 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 |
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| Abstract: | Pre-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. |
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| Keywords: | acute myeloid leukaemia allogeneic haematopoietic cell transplantation measurable residual disease post-transplant cyclophosphamide unrelated donor |
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