TNF-Inhibition with Etanercept for Graft-versus-Host Disease Prevention in High-Risk HCT: Lower TNFR1 Levels Correlate with Better Outcomes

Sung W. Choi, Patrick Stiff, Kenneth Cooke, James L.M. Ferrara, Thomas Braun, Carrie Kitko, Pavan Reddy, Gregory Yanik, Shin Mineishi, Sophie Paczesny, David Hanauer, Attaphol Pawarode, Edward Peres, Tulio Rodrigue, Scott Smith, John E. Levine

Research output: Contribution to journalArticle

35 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1525-1532
Number of pages8
JournalBiology of Blood and Marrow Transplantation
Volume18
Issue number10
DOIs
StatePublished - Oct 1 2012

All Science Journal Classification (ASJC) codes

  • Hematology
  • Transplantation

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    Choi, S. W., Stiff, P., Cooke, K., Ferrara, J. L. M., Braun, T., Kitko, C., Reddy, P., Yanik, G., Mineishi, S., Paczesny, S., Hanauer, D., Pawarode, A., Peres, E., Rodrigue, T., Smith, S., & Levine, J. E. (2012). TNF-Inhibition with Etanercept for Graft-versus-Host Disease Prevention in High-Risk HCT: Lower TNFR1 Levels Correlate with Better Outcomes. Biology of Blood and Marrow Transplantation, 18(10), 1525-1532. https://doi.org/10.1016/j.bbmt.2012.03.013