TNF-inhibition with etanercept for graft-versus-host disease prevention in high-risk HCT: lower TNFR1 levels correlate with better outcomes Journal Article

Local Library Link: Find It @ Loyola

Authors: Choi, S. W.; Stiff, P; Cooke, K.; Ferrara, J. L.; Braun, T.; Kitko, C.; Reddy, P.; Yanik, G.; Mineishi, S.; Paczesny, S.; Hanauer, D.; Pawarode, A; Peres, E.; Rodriguez, T; Smith, S; Levine, J. E.
Article Title: TNF-inhibition with etanercept for graft-versus-host disease prevention in high-risk HCT: lower TNFR1 levels correlate with better outcomes
Abstract: Graft-versus-host disease (GVHD) causes most non-relapse mortality (NRM) after alternative donor (unrelated and mismatched related) hematopoietic cell transplant (HCT). We previously showed that increases in day +7 TNF-receptor-1 (TNFR1) ratios (posttransplantation day +7/pretransplantation baseline) after myeloablative HCT correlate with outcomes including GVHD, NRM, and survival. Therefore, we conducted a phase II trial at 2 centers, testing whether the addition of the TNF-inhibitor etanercept (25 mg twice weekly from start of conditioning to day +56) to standard GVHD prophylaxis would lower TNFR1 levels, reduce GVHD rates, and improve NRM and survival. Patients underwent myeloablative HCT from a matched unrelated donor (URD; N = 71), 1-antigen mismatched URD (N = 26), or 1-antigen mismatched related donor (N = 3) using either total body irradiation (TBI)-based conditioning (N = 29) or non-TBI-based conditioning (N = 71). Compared to historical controls, the increase in posttransplantation day +7 TNFR1 ratios was not altered in patients who received TBI-based conditioning, but was 40% lower in patients receiving non-TBI-based conditioning. The latter group experienced relatively low rates of severe grade 3 to 4 GVHD (14%), 1-year NRM (16%), and high 1-year survival (69%). These findings suggest that (1) the effectiveness of TNF-inhibition with etanercept may depend on the conditioning regimen, and (2) attenuating the expected rise in TNFR1 levels early posttransplantation correlates with good outcomes.
Journal Title: Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation
Volume: 18
Issue: 10
ISSN: 1523-6536; 1083-8791
Publisher: Elsevier Inc  
Journal Place: United States
Date Published: 2012
Start Page: 1525
End Page: 1532
Language: eng
DOI/URL:

10.1016/j.bbmt.2012.03.013
Notes: LR: 20131112; CI: Copyright (c) 2012; GR: 2P01CA039542/CA/NCI NIH HHS/United States; GR: 5P30CA046592/CA/NCI NIH HHS/United States; GR: AI091623-01/AI/NIAID NIH HHS/United States; GR: K23 AI091623/AI/NIAID NIH HHS/United States; GR: P01 CA039542/CA/NCI NIH HHS/United States; JID: 9600628; 0 (Immunoglobulin G); 0 (Immunosuppressive Agents); 0 (Receptors, Tumor Necrosis Factor); 0 (Receptors, Tumor Necrosis Factor, Type I); 185243-69-0 (TNFR-Fc fusion protein); NIHMS382262; OID: NLM: NIHMS382262; OID: NLM: PMC3443302; 2012/02/06 [received]; 2012/03/25 [accepted]; 2012/03/30 [aheadofprint]; ppublish