High-dose alemtuzumab and cyclosporine vs tacrolimus, methotrexate, and sirolimus for chronic graft-versus-host disease prevention.

Autor:	Holtzman NG; Immune Deficiency Cellular Therapy Program, National Cancer Institute, National Institutes of Health, Bethesda, MD., Curtis LM; Experimental Transplantation and Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD.; Ascension Maryland Saint Agnes Hospital, Baltimore, MD., Salit RB; Experimental Transplantation and Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD.; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA., Shaffer BC; Experimental Transplantation and Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD.; Adult Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY., Pirsl F; Immune Deficiency Cellular Therapy Program, National Cancer Institute, National Institutes of Health, Bethesda, MD., Ostojic A; Immune Deficiency Cellular Therapy Program, National Cancer Institute, National Institutes of Health, Bethesda, MD., Steinberg SM; Biostatistics and Data Management Section, National Cancer Institute, National Institutes of Health, Bethesda, MD., Schulz E; Immune Deficiency Cellular Therapy Program, National Cancer Institute, National Institutes of Health, Bethesda, MD., Wilder JS; Frederick National Laboratory for Cancer Research, Clinical Monitoring Research Program, Leidos Biomedical Research, Inc, Frederick, MD., Hughes TE; Department of Pharmacy, Clinical Center, National Institutes of Health, Bethesda, MD., Rose J; Experimental Transplantation and Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD., Memon S; Experimental Transplantation and Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD., Korngold R; John Theurer Cancer Center, Hackensack University Medical Center, Hackensack, NJ., Gea-Banacloche JC; National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD., Fowler DH; Experimental Transplantation and Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD.; Rapa Therapeutics, Rockville, MD., Hakim FT; Experimental Transplantation and Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD., Gress RE; Experimental Transplantation and Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD., Bishop MR; Experimental Transplantation and Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD.; Department of Hematology/Oncology, David and Etta Jonas Center for Cellular Therapy, University of Chicago, Chicago, IL., Pavletic SZ; Immune Deficiency Cellular Therapy Program, National Cancer Institute, National Institutes of Health, Bethesda, MD.
Jazyk:	angličtina
Zdroj:	Blood advances [Blood Adv] 2024 Aug 27; Vol. 8 (16), pp. 4294-4310.
DOI:	10.1182/bloodadvances.2023010973
Abstrakt:	Abstract: Chronic graft-versus-host disease (cGVHD) remains a significant problem for patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Although in vivo lymphodepletion for cGVHD prophylaxis has been explored in the myeloablative setting, its effects after reduced-intensity conditioning (RIC) are not well described. Patients (N = 83) with hematologic malignancies underwent targeted lymphodepletion chemotherapy followed by a RIC allo-HSCT using peripheral blood stem cells from unrelated donors. Patients were randomized to 2 GVHD prophylaxis arms: alemtuzumab and cyclosporine (AC; n = 44) or tacrolimus, methotrexate, and sirolimus (TMS; n = 39), with the primary end point of cumulative incidence of severe cGVHD. The incidence of severe cGVHD was lower with AC vs TMS prophylaxis at 1- and 5-years (0% vs 10.3% and 4.5% vs 28.5%; overall, P = .0002), as well as any grade (P = .003) and moderate-severe (P < .0001) cGVHD. AC was associated with higher rates of grade 3 to 4 infections (P = .02) and relapse (52% vs 21%; P = .003) with no difference in 5-year GVHD-free-, relapse-free-, or overall survival. AC severely depleted naïve T-cell reconstitution, resulting in reduced T-cell receptor repertoire diversity, smaller populations of CD4Treg and CD8Tscm, but a higher ratio of Treg to naïve T-cells at 6 months. In summary, an alemtuzumab-based regimen successfully reduced the rate and severity of cGVHD after RIC allo-HSCT and resulted in a distinct immunomodulatory profile, which may have reduced cGVHD incidence and severity. However, increased infections and relapse resulted in a lack of survival benefit after long-term follow-up. This trial was registered at www.ClinicalTrials.gov as #NCT00520130. (Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution.)
Databáze:	MEDLINE
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