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SHR Neuro Cancer Cardio Lipid Metab Microb

Holtzman, NG; Curtis, LM; Salit, RB; Shaffer, BC; Pirsl, F; Ostojic, A; Steinberg, SM; Schulz, E; Wilder, JS; Hughes, TE; Rose, J; Memon, S; Korngold, R; Gea-Banacloche, JC; Fowler, DH; Hakim, FT; Gress, RE; Bishop, MR; Pavletic, SZ.
High-dose alemtuzumab and cyclosporine vs tacrolimus, methotrexate, and sirolimus for chronic graft-versus-host disease prevention.
Blood Adv. 2024; 8(16):4294-4310 Doi: 10.1182/bloodadvances.2023010973 [OPEN ACCESS]
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Co-authors Med Uni Graz: Schulz Eduard
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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.
Find related publications in this database (using NLM MeSH Indexing): Adult - administration & dosage; Aged - administration & dosage; Female - administration & dosage; Humans - administration & dosage; Male - administration & dosage; Middle Aged - administration & dosage; Young Adult - administration & dosage; Alemtuzumab - therapeutic use, administration & dosage; Chronic Disease - prevention & control; Cyclosporine - therapeutic use, administration & dosage; Graft vs Host Disease - epidemiology, etiology, prevention & control; Hematologic Neoplasms - therapy; Hematopoietic Stem Cell Transplantation - adverse effects; Immunosuppressive Agents - administration & dosage, therapeutic use; Methotrexate - therapeutic use, administration & dosage; Sirolimus - administration & dosage, therapeutic use; Tacrolimus - administration & dosage, therapeutic use; Transplantation Conditioning - methods; Transplantation, Homologous - adverse effects