Post-transplant cyclophosphamide separates graft-versus host disease and graft versus leukemia effects after HLA-matched stem-cell transplantation for acute myeloid leukemia
The association of graft-versus-host disease (GVHD) and graft-versus-leukemia (GVL) effects after allogeneic stem-cell transplantation (SCT) is well-established but was not confirmed in the modern era and following post-transplant cyclophosphamide (PTCy). We assessed GVHD/ GVL association in AML patients following HLA-matched SCT with standard calcineurin-based (n = 12,653, 57% with additional in-vivo T-cell depletion) or PTCy-based (n = 508) GVHD prophylaxis. Following standard prophylaxis, acute GVHD grade II-IV and III-IV, chronic GVHD, and extensive chronic GVHD rates were 23.8%, 7.5%, 37.0%, and 16.3%, respectively. Acute GVHD grade II and III-IV were associated with lower relapse [hazard-ratio (HR) 0.85, P = 0.002; HR 0.76, P = 0.003, respectively)], higher non-relapse mortality (NRM) (HR 1.5, P < 0.001; HR 6.21, P < 0.001) and lower overall survival (OS) (HR 1.49, P < 0.001; HR 6.1, P < 0.001). Extensive chronic GVHD predicted lower relapse (HR 0.69, P < 0.001), higher NRM (HR 2.83, P < 0.001), and lower OS (HR 2.74, P < 0.001). Following PTCy, GVHD rates were 22.8%, 6.2%, 35.5%, and 17.7%, respectively. Acute GVHD was not associated with relapse (HR 1.37, P = 0.15) but predicted higher NRM (HR 3.34, P < 0.001) and lower OS (HR 1.92, P = 0.001). Chronic GVHD was not prognostic for these outcomes. In conclusion, GVHD and GVL are strongly associated with contemporary SCT. However, following PTCy, GVHD is not associated with reduced relapse.
Authors
- Nicolaus Martin Kröger (ORCID: https://orcid.org/0000-0001-5103-9966)
- Avichai Shimoni (ORCID: https://orcid.org/0000-0001-8782-6160)
- Mohamad Mohty (ORCID: https://orcid.org/0000-0002-7264-808X)
- Fabio Ciceri (ORCID: https://orcid.org/0000-0003-0873-0123)
- Alexander Kulagin (ORCID: https://orcid.org/0000-0002-9589-4136)
- Jaime Sanz (ORCID: https://orcid.org/0000-0001-6934-4619)
- Myriam Labopin (ORCID: https://orcid.org/0000-0003-4514-4748)
- Jan Vydra (ORCID: https://orcid.org/0000-0002-4274-3895)
- Patrizia Chiusolo (ORCID: https://orcid.org/0000-0002-1355-1587)
- Christophe Peczynski (ORCID: https://orcid.org/0000-0002-3829-0088)
- José L. Díez‐Martín (ORCID: https://orcid.org/0000-0003-1869-0129)
- Arnon Nagler (ORCID: https://orcid.org/0000-0002-0763-1265)
- Jan J. Cornelissen (ORCID: https://orcid.org/0000-0002-1864-4598)
- Carlos Solano (ORCID: https://orcid.org/0000-0003-3702-0817)
- Amit Patel (ORCID: https://orcid.org/0000-0003-0029-4611)
- Yener Koç (ORCID: https://orcid.org/0000-0002-3919-9649)
- Gwendolyn Van Gorkom (ORCID: https://orcid.org/0000-0001-7327-7834)
- Ellen Meijer
- Montserrat Rovira
- Goda Choi (ORCID: https://orcid.org/0000-0003-2348-5947)
Institutions
- University Medical Center Groningen (NL)
- University of Liverpool (GB)
- Inserm (FR)
- Universität Hamburg (DE)
- Tel Aviv University (IL)
- First Pavlov State Medical University of St. Petersburg (RU)
- Sheba Medical Center (IL)
- Maastricht University Medical Centre (NL)
- Royal Liverpool University Hospital (GB)
- Clatterbridge Cancer Centre NHS Foundation Trust (GB)
- Hospital General Universitario Gregorio Marañón (ES)
- Hospital Universitari i Politècnic La Fe (ES)
- Sorbonne Université (FR)
- Hospital Clínico Universitario de Valencia (ES)
- Institute of Haematology and Blood Transfusion (CZ)
- Hôpital Saint-Antoine (FR)
- University Medical Center Hamburg-Eppendorf (DE)
- Hospital Clínic de Barcelona (ES)
- Istituto di Ematologia di Bologna (IT)
- Centre de Recherche Saint-Antoine (FR)
- Erasmus MC Cancer Institute (NL)
- Amsterdam UMC Location Vrije Universiteit Amsterdam (NL)
Publication Details
- Journal
- Leukemia
- Published
- 2024-10-31
- DOI
- https://doi.org/10.1038/s41375-024-02445-x
- Citations
- 7
- Primary Topic
- Hematopoietic Stem Cell Transplantation
- Type
- article
- Field-Weighted Citation Impact
- 3.18
Funders
- Tel Aviv University