Nicole Santoro1, Myriam Labopin2,3, Fabio Ciceri4, Maria Teresa Van Lint5, Daniela Nasso6, Didier Blaise7, William Arcese6, Johanna Tischer8, Benedetto Bruno9, Gerhard Ehninger10, Yener Koc11, Stella Santarone12, Xiao-Jun Huang13, Bipin N Savani3,14, Mohamad Mohty2,3, Annalisa Ruggeri15,16, Arnon Nagler3,17. 1. Section of Hematology, Department of Medicine, University of Perugia, Centro Ricerche Emato-Oncologiche, Perugia, Italy. 2. Department of Hematology and Cell Therapy, Saint-Antoine Hospital, Paris, France. 3. ALWP Office, Saint-Antoine Hospital, Paris, France. 4. Hematology and Bone Marrow Transplantation Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy. 5. San Martino Hospital, Department of Haematology II, Genova, Italy. 6. Rome Transplant Network, Tor Vergata, University of Rome, Stem Cell Transplant Unit, Policlinico Universitario Tor Vergata, Rome, Italy. 7. Bone Marrow Transplantation Unit, Cancer Research Center, Institute Paoli Calmettes, Marseille, France. 8. University Hospital of Munich-Grosshadern, LMU, Department of Internal Medicine III, Munich, Germany. 9. S.S.C.V.D Trapianto di Cellule Staminali, A.O.U Citta della Salute e della Scienza di Torino, Presidio Molinette, Torino, Italy. 10. Universitaets Klinikum Dresden, Medizinische Klinik und Poliklinik I, Dresden, Germany. 11. Medical Park Hospitals, Stem Cell Transplant Unit, Antalya, Turkey. 12. Ospedale Civile, Dipartimento di Ematologia, Medicina Trasfusionale e Biotecnologie, Pescara, Italy. 13. Peking University People's Hospital, Institute of Haematology, Beijing, China. 14. Vanderbilt University Medical center, Nashville, Tennessee. 15. Department of Pediatric Hematology and Oncology, IRCCS Bambino Gesù Children's Hospital, Rome, Italy. 16. Cellular Therapy and Immunobiology Working Party of EBMT. 17. Department of Hematology and Bone Marrow Transplantation, Chaim Sheba Medical Center, Tel Hashomer, Israel.
Abstract
BACKGROUND: T cell-replete haploidentical stem cell transplantation (haplo-SCT) is a valid therapeutic option for adult patients with high-risk acute myeloid leukemia (AML) lacking an HLA-matched sibling or unrelated donor. METHOD: We retrospectively analyzed the outcomes of 912 AML patients ≥45 years of age who had undergone haplo-SCT with either myeloablative conditioning (MAC; n = 373) or reduced intensity conditioning (RIC; n = 539) regimens. RESULTS: The median follow-up was 31.1 and 25.7 months for MAC and RIC, respectively. The incidence of relapse and nonrelapse mortality (NRM) were 25.1% versus 28.7% and 31.0% versus 30.3% for MAC and RIC, respectively; 2-year leukemia-free survival (LFS) was 43.9% for MAC versus 41.0% for RIC. In multivariate analysis, the use of MAC versus RIC was not associated with a difference in the outcomes. Results were confirmed in the propensity score-weighted analysis. Disease status and performance status at transplantation were associated with outcomes. Notably, the use of posttransplantation cyclophosphamide was associated with reduced acute graft-versus-host disease (aGVHD) stage III-IV, and NRM and increased overall survival, LFS, and GVHD-free, relapse-free survival. The use of mobilized peripheral blood stem cells was associated with an increased risk of stage II-IV aGVHD. CONCLUSION: No differences were found between MAC and RIC regimens for haplo-SCT in adults with AML who were ≥45 years of age. The type of GVHD prophylaxis, disease status, and performance status were the major predictors of transplantation outcome. These results may serve as the background for randomized study comparing RIC versus MAC for haplo-SCT in adults with AML.
BACKGROUND: T cell-replete haploidentical stem cell transplantation (haplo-SCT) is a valid therapeutic option for adult patients with high-risk acute myeloid leukemia (AML) lacking an HLA-matched sibling or unrelated donor. METHOD: We retrospectively analyzed the outcomes of 912 AMLpatients ≥45 years of age who had undergone haplo-SCT with either myeloablative conditioning (MAC; n = 373) or reduced intensity conditioning (RIC; n = 539) regimens. RESULTS: The median follow-up was 31.1 and 25.7 months for MAC and RIC, respectively. The incidence of relapse and nonrelapse mortality (NRM) were 25.1% versus 28.7% and 31.0% versus 30.3% for MAC and RIC, respectively; 2-year leukemia-free survival (LFS) was 43.9% for MAC versus 41.0% for RIC. In multivariate analysis, the use of MAC versus RIC was not associated with a difference in the outcomes. Results were confirmed in the propensity score-weighted analysis. Disease status and performance status at transplantation were associated with outcomes. Notably, the use of posttransplantation cyclophosphamide was associated with reduced acute graft-versus-host disease (aGVHD) stage III-IV, and NRM and increased overall survival, LFS, and GVHD-free, relapse-free survival. The use of mobilized peripheral blood stem cells was associated with an increased risk of stage II-IV aGVHD. CONCLUSION: No differences were found between MAC and RIC regimens for haplo-SCT in adults with AML who were ≥45 years of age. The type of GVHD prophylaxis, disease status, and performance status were the major predictors of transplantation outcome. These results may serve as the background for randomized study comparing RIC versus MAC for haplo-SCT in adults with AML.
Authors: Melissa M Berrien-Elliott; Jennifer A Foltz; David A Russler-Germain; Carly C Neal; Jennifer Tran; Margery Gang; Pamela Wong; Bryan Fisk; Celia C Cubitt; Nancy D Marin; Alice Y Zhou; Miriam T Jacobs; Mark Foster; Timothy Schappe; Ethan McClain; Samantha Kersting-Schadek; Sweta Desai; Patrick Pence; Michelle Becker-Hapak; Jeremy Eisele; Matthew Mosior; Lynne Marsala; Obi L Griffith; Malachi Griffith; Saad M Khan; David H Spencer; John F DiPersio; Rizwan Romee; Geoffrey L Uy; Camille N Abboud; Armin Ghobadi; Peter Westervelt; Keith Stockerl-Goldstein; Mark A Schroeder; Fei Wan; Wen-Rong Lie; Patrick Soon-Shiong; Allegra A Petti; Amanda F Cashen; Todd A Fehniger Journal: Sci Transl Med Date: 2022-02-23 Impact factor: 19.319