Methotrexate Versus Mycophenolate Mofetil Prophylaxis in Allogeneic Hematopoietic Cell Transplantation for Chronic Myeloid Malignancies: A Retrospective Analysis on Behalf of the Chronic Malignancies Working Party of the <scp>EBMT</scp>
Prophylaxis strategies for Graft versus host disease (GVHD) in allogeneic hematopoietic cell transplantation (allo-HCT) frequently encompass a combination of a calcineurin inhibitor (CNI) with either methotrexate (MTX) or mycophenolate mofetil (MMF). The aim of this retrospective, EBMT registry-based study was to determine outcome differences for chronic myeloid malignancies and secondary acute myeloid leukemia (sAML) between MTX- and MMF-based prophylaxis regimens while taking potential heterogeneity between subgroups into consideration. Eligible were patients transplanted between 2007 and 2017 who received either MTX- or MMF prophylaxis in combination with a CNI. Endpoints after allo-HCT were overall survival, relapse-free survival (RFS), relapse incidence, non-relapse mortality (NRM), and Grades 2-4 acute GVHD (aGvHD). Overall, 13 699 patients from 321 centers were included. Median follow-up was 42.8 months (IQR 19.8-74.5 months). MTX prophylaxis was associated with reduced overall mortality (HR 0.87, 95% CI 0.81-0.95, p = 0.001) and NRM (HR 0.86, 95% CI 0.78-0.96, p = 0.006) compared with MMF in multivariable Cox regression models in the whole cohort without significant interaction between prophylaxis and subgroups. In contrast, there was no significant association of prophylaxis with risk of relapse (HR 1.03 MTX vs. MMF, 95% CI 0.94-1.14, p = 0.53) or RFS (HR 0.95, 95% CI 0.88-1.01, p = 0.12). There was a reduced risk of Grades 2-4 acute GVHD and reduced mortality after acute GVHD with MTX prophylaxis but no association with outcome in a landmark analysis in patients without aGvHD at 3 months after allo-HCT. In conclusion, MTX-complemented CNI prophylaxis was associated with favorable survival, and with favorable survival after aGVHD compared with MMF.
Authors
- Kavita K Raj (ORCID: https://orcid.org/0000-0002-8258-354X)
- Nicolaus Martin Kröger (ORCID: https://orcid.org/0000-0001-5103-9966)
- Liesbeth C. de Wreede (ORCID: https://orcid.org/0000-0002-7667-9369)
- Matthias Stelljes (ORCID: https://orcid.org/0000-0002-9331-5145)
- Marie Robin (ORCID: https://orcid.org/0000-0003-1388-9876)
- Urpu Salmenniemi (ORCID: https://orcid.org/0009-0002-2053-3384)
- Donal P. McLornan (ORCID: https://orcid.org/0000-0003-1224-091X)
- Wolfgang Andreas Bethge (ORCID: https://orcid.org/0000-0001-6052-2618)
- Matthias Eder (ORCID: https://orcid.org/0000-0002-5110-0744)
- Henrik Sengeløv (ORCID: https://orcid.org/0000-0002-5991-2958)
- Luuk Gras
- Anastasia Pouli
- Ibrahim Yakoub‐Agha (ORCID: https://orcid.org/0000-0003-4524-8782)
- Thomas Luft (ORCID: https://orcid.org/0000-0002-0387-1640)
- Igor Wolfgang Blau (ORCID: https://orcid.org/0000-0003-1416-819X)
- Joanna Ewa Drozd-Sokolowska (ORCID: https://orcid.org/0000-0002-4562-6264)
- Thomas A. Schroeder (ORCID: https://orcid.org/0000-0002-1653-7959)
- Katja Sockel (ORCID: https://orcid.org/0000-0003-1732-7299)
- Uwe Platzbecker (ORCID: https://orcid.org/0000-0003-1863-3239)
- Régis Peffault de Latour (ORCID: https://orcid.org/0000-0001-6222-4753)
- Peter Dreger (ORCID: https://orcid.org/0000-0002-7429-8570)
- Johan A. Maertens (ORCID: https://orcid.org/0000-0003-4257-5980)
- Linda Köster
- Guido Kobbe
Institutions
- University of Copenhagen (DK)
- Karolinska University Hospital (SE)
- University College London Hospitals NHS Foundation Trust (GB)
- Inserm (FR)
- Universität Hamburg (DE)
- Heidelberg University (DE)
- University of Münster (DE)
- Université de Lille (FR)
- Medical University of Warsaw (PL)
- Leiden University Medical Center (NL)
- Universitair Ziekenhuis Leuven (BE)
- Helsinki University Hospital (FI)
- Centre Hospitalier Universitaire de Lille (FR)
- Medizinische Hochschule Hannover (DE)
- European Society for Blood and Marrow Transplantation (NL)
- University Medical Center Hamburg-Eppendorf (DE)
- St Savas Hospital (GR)
- University Hospital Leipzig (DE)
- Central Clinical Hospital (PL)
- Hôpital Saint-Louis (FR)
- West German Heart and Vascular Center Essen (DE)
- Heinrich Heine University Düsseldorf (DE)
- University College London (GB)
- Technische Universität Dresden (DE)
- Charité - Universitätsmedizin Berlin (DE)
Publication Details
- Journal
- American Journal of Hematology
- Published
- 2024-11-28
- DOI
- https://doi.org/10.1002/ajh.27531
- Citations
- 2
- Primary Topic
- Hematopoietic Stem Cell Transplantation
- Type
- article
- Field-Weighted Citation Impact
- 0.91