دورية أكاديمية
High-dose Alemtuzumab-Cyclosporine vs Tacrolimus-Methotrexate-Sirolimus for Chronic Graft-versus-Host Disease Prevention.
| العنوان: | High-dose Alemtuzumab-Cyclosporine vs Tacrolimus-Methotrexate-Sirolimus for Chronic Graft-versus-Host Disease Prevention. |
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| المؤلفون: | Holtzman NG; National Cancer Institute, Center for Cancer Research, Bethesda, Maryland, United States., Curtis LM; Ascension Maryland Saint Agnes Hospital, United States., Salit RB; National Cancer Institute, National Institutes of Health, United States., Shaffer BC; National Cancer Institute, National Institutes of Health, United States., Pirsl F; National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States., Ostojic A; National Cancer Institute, Center for Cancer Research, Bethesda, Maryland, United States., Steinberg SM; Biostatistics and Data Management Section, National Cancer Institute, NIH, Bethesda, Maryland, United States., Schulz E; Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States., Wilder JS; National Institutes of Health, Bethesda, Maryland, United States., Hughes TE; National Institutes of Health, Bethesda, Maryland, United States., Rose J; NCI, Bethesda, Maryland, United States., Memon S; National Institutes of Health, Bethesda, Maryland, United States., Korngold R; Hackensack Meridian Health, Nutley, New Jersey, United States., Gea-Banacloche J; National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, United States., Fowler DH; Rapa Therapeutics, United States., Hakim FT; National Cancer Institute, Bethesda, Maryland, United States., Gress RE; National Cancer Institute, Bethesda, Maryland, United States., Bishop MR; The David and Etta Jonas Center for Cellular Therapy, University of Chicago, Chicago, Illinois, United States., Pavletic SZ; National Cancer Institute, Bethesda, Maryland, United States. |
| المصدر: | Blood advances [Blood Adv] 2024 Apr 26. Date of Electronic Publication: 2024 Apr 26. |
| Publication Model: | Ahead of Print |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Society of Hematology Country of Publication: United States NLM ID: 101698425 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2473-9537 (Electronic) Linking ISSN: 24739529 NLM ISO Abbreviation: Blood Adv Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Washington, DC : American Society of Hematology, [2016]- |
| مستخلص: | Chronic graft-versus-host disease (cGVHD) remains a significant problem for patients after allogeneic hematopoietic stem cell transplants (allo-HSCT). While in vivo lymphodepletion by antibodies 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 two GVHD prophylaxis arms: high-dose alemtuzumab/cyclosporine (AC, n=44) and tacrolimus/methotrexate/sirolimus (TMS, n=39) with the primary endpoint 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=0.0002), as well as any grade (p=0.003) and moderate-severe (p<0.0001) cGVHD. AC was associated with higher rates of grade III-IV infections (p=0.02) and relapse (52% vs 21%, p=0.003) with a shorter 5-year PFS (18% vs 41%, p=0.01) and no difference in 5-year GRFS, OS, or NRM. AC severely depleted naïve T-cells reconstitution, resulting in reduced TCR repertoire diversity, smaller populations of CD4 Treg and CD8 Tscm, 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. ClinicalTrials.gov identifier: NCT00520130. (Copyright © 2024 American Society of Hematology.) |
| سلسلة جزيئية: | ClinicalTrials.gov NCT00520130 |
| تواريخ الأحداث: | Date Created: 20240426 Latest Revision: 20240426 |
| رمز التحديث: | 20240427 |
| DOI: | 10.1182/bloodadvances.2023010973 |
| PMID: | 38669315 |
| قاعدة البيانات: | MEDLINE |
Full Text via ClinicalKey 
Full Text Finder | تدمد: | 2473-9537 |
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| DOI: | 10.1182/bloodadvances.2023010973 |