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Post-transplant cyclophosphamide separates graft-versus host disease and graft versus leukemia effects after HLA-matched stem-cell transplantation for acute myeloid leukemia
A. Shimoni, C. Peczynski, M. Labopin, A. Kulagin, E. Meijer, J. Cornelissen, G. Choi, J. Sanz, M. Rovira, G. Van Gorkom, N. Kröger, Y. Koc, J. Vydra, JL. Diez-Martin, C. Solano, A. Patel, P. Chiusolo, F. Ciceri, A. Nagler, M. Mohty
Language English Country England, Great Britain
Document type Journal Article
- MeSH
- Leukemia, Myeloid, Acute * therapy MeSH
- Cyclophosphamide * therapeutic use MeSH
- Adult MeSH
- HLA Antigens immunology MeSH
- Transplantation, Homologous MeSH
- Immunosuppressive Agents therapeutic use MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Graft vs Host Disease * etiology prevention & control MeSH
- Graft vs Leukemia Effect * MeSH
- Aged MeSH
- Histocompatibility Testing MeSH
- Hematopoietic Stem Cell Transplantation * adverse effects methods MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
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.
Gorbacheva Research Institute Pavlov University St Petersburg Russia
Hématologie Clinique et Thérapie Cellulaire Hôpital Saint Antoine Paris France
Hematology and Bone Marrow Transplant Unit San Raffaele Scientific Institute Milan Italy
Hospital Clinic Institute of Hematology and Oncology Dept of Hematology Barcelona Spain
Hospital Clínico de Valencia Servicio de Hematología Valencia Spain
Hospital Gregorio Marañón Sección de Trasplante de Medula Osea Madrid Spain
Institute of Hematology and Blood Transfusion Servicio de Hematología Prague Czech Republic
Medicana International Hospital Istanbul Bone Marrow Transplant Unit Istanbul Turkey
Sorbonne University INSERM UMRs 938 Paris France
Universita Cattolica S Cuore Istituto di Ematologia Ematologia Rome Italy
University Hospital Eppendorf Bone Marrow Transplantation Centre Hamburg Germany
University Hospital La Fe Hematology Department Valencia Spain
University Hospital Maastricht Dept Internal Med Hematology Oncology Maastricht The Netherlands
University Medical Center Groningen Dept of Hematology Groningen The Netherlands
VU University Medical Center Department of Hematology Amsterdam The Netherlands
References provided by Crossref.org
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