Title | TNF-inhibition with etanercept for graft-versus-host disease prevention in high-risk HCT: lower TNFR1 levels correlate with better outcomes. |
Publication Type | Journal Article |
Year of Publication | 2012 |
Authors | Choi, SW, Stiff, P, Cooke, K, Ferrara, JLM, Braun, T, Kitko, C, Reddy, P, Yanik, G, Mineishi, S, Paczesny, S, Hanauer, DA, Pawarode, A, Peres, E, Rodriguez, T, Smith, S, Levine, JE |
Journal | Biol Blood Marrow Transplant |
Volume | 18 |
Issue | 10 |
Pagination | 1525-32 |
Date Published | 2012 Oct |
ISSN | 1523-6536 |
Keywords | Adolescent, Adult, Child, Child, Preschool, Drug Administration Schedule, Female, Gene Expression, Graft vs Host Disease, Hematologic Neoplasms, Hematopoietic Stem Cell Transplantation, Histocompatibility Testing, Humans, Immunoglobulin G, Immunosuppressive Agents, Male, Middle Aged, Receptors, Tumor Necrosis Factor, Receptors, Tumor Necrosis Factor, Type I, Severity of Illness Index, Survival Analysis, Tissue Donors, Transplantation Conditioning, Whole-Body Irradiation |
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. |
DOI | 10.1016/j.bbmt.2012.03.013 |
Alternate Journal | Biol. Blood Marrow Transplant. |
PubMed ID | 22469883 |
PubMed Central ID | PMC3443302 |
Grant List | 2P01CA039542 / CA / NCI NIH HHS / United States 5P30CA046592 / CA / NCI NIH HHS / United States AI091623-01 / AI / NIAID NIH HHS / United States K23 AI091623 / AI / NIAID NIH HHS / United States P01 CA039542 / CA / NCI NIH HHS / United States |
Research reported in this publication was supported by the National Cancer Institutes of
Health under Award Number P30CA046592. The content is solely the responsibility
of the authors and does not necessarily represent the official views of the
National Institutes of Health.
Research reported in this publication was supported by the National Cancer Institutes of
Health under Award Number P30CA046592 by the use of the following Cancer Center
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