High-dose alemtuzumab and cyclosporine vs tacrolimus, methotrexate, and sirolimus for chronic graft-versus-host disease prevention Journal Article
| Authors: | Holtzman, N. G.; Curtis, L. M.; Salit, R. B.; Shaffer, B. C.; Pirsl, F.; Ostojic, A.; Steinberg, S. M.; Schulz, E.; Wilder, J. S.; Hughes, T. E.; Rose, J.; Memon, S.; Korngold, R.; Gea-Banacloche, J. C.; Fowler, D. H.; Hakim, F. T.; Gress, R. E.; Bishop, M. R.; Pavletic, S. Z. |
| Article Title: | High-dose alemtuzumab and cyclosporine vs tacrolimus, methotrexate, and sirolimus for chronic graft-versus-host disease prevention |
| 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 longterm follow-up. © 2024 American Society of Hematology. All rights reserved. |
| Keywords: | adult; cancer chemotherapy; controlled study; aged; major clinical study; overall survival; mortality; drug dose reduction; methotrexate; drug megadose; cd8+ t lymphocyte; cell survival; cd34 antigen; randomized controlled trial; acute lymphoblastic leukemia; t lymphocyte receptor; regulatory t lymphocyte; chronic graft versus host disease; engraftment; prophylaxis; cd4+ t lymphocyte; hematopoietic cell; reduced intensity conditioning; interleukin 6; immunomodulation; gamma interferon inducible protein 10; tacrolimus; granulocyte colony stimulating factor; sirolimus; cyclosporine; alemtuzumab; national institutes of health stroke scale; cd45ra antigen; tumor necrosis factor; premedication; recurrence free survival; cxcl9 chemokine; cumulative incidence; immune reconstitution; absolute lymphocyte count; human; male; female; article; b cell activating factor; interleukin 1 receptor like 1 protein |
| Journal Title: | Blood Advances |
| Volume: | 8 |
| Issue: | 16 |
| ISSN: | 2473-9529 |
| Publisher: | American Society of Hematology |
| Date Published: | 2024-08-27 |
| Start Page: | 4294 |
| End Page: | 4310 |
| Language: | English |
| DOI: | 10.1182/bloodadvances.2023010973 |
| PUBMED: | 38669315 |
| PROVIDER: | scopus |
| PMCID: | PMC11372812 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
