Etanercept plus topical corticosteroids as initial therapy for grade one acute graft-versus-host disease after allogeneic hematopoietic cell transplantation

Erin Gatza, Thomas Braun, John E. Levine, James L.M. Ferrara, Shuang Zhao, Tianyi Wang, Lawrence Chang, Andrew Harris, Attaphol Pawarode, Carrie Kitko, John M. Magenau, Gregory A. Yanik, Daniel R. Couriel, Steven Goldstein, James Connelly, Pavan Reddy, Sophie Paczesny, Sung Won Choi

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Clinical diagnosis of grade 1 acute graft-versus-host disease (GVHD) marks the beginning of a potentially progressive and fatal course of GVHD after hematopoietic stem cell transplantation (HSCT). However, interventional studies to treat early GVHD are lacking. We conducted a single-arm prospective phase II trial to test the hypothesis that treatment of newly diagnosed grade 1 acute GVHD with etanercept and topical corticosteroids would reduce progression to grade 2 to 4 within 28days. Study patients (n=34) had a median age of 51years (range, 10 to 67years) and had undergone unrelated (n=22) or related (n=12) donor HSCT. Study patients were treated with etanercept (4mg/kg, maximum 25mg/dose) twice weekly for 4 to 8weeks. Ten of 34 patients (29%) progressed to grade 2 to 4 acute GVHD within 28days. The cumulative incidence of grade 2 to 4 and grade 3 to 4 acute GVHD at 1year was 41% and 3%, respectively. Nonrelapse mortality was 19% and overall survival was 63% at 2years. Among a contemporaneous control cohort of patients who were diagnosed with grade 1 acute GVHD and treated with topical corticosteroids but not etanercept during the study period, 12 of 28 patients (43%) progressed to grade 2 to 4 GVHD within 28days, with a 1-year incidence of grade 2 to 4 GVHD and grade 3 to 4 GVHD of 61% (41% versus 61%, P=08) and 18% (3% versus 18%, P=05), respectively. Patients treated with etanercept also experienced less increase in GVHD plasma biomarkers suppression of tumorigenicity 2 (P=06) and regenerating islet-derived 3-alpha (P=01) 28days after grade 1 acute GVHD diagnosis compared with contemporaneous control patients. This study was terminated early because of poor accrual. Future prospective studies are needed to identify patients with grade 1 acute GVHD at risk of swift progression to more severe GVHD and to establish consensus for the treatment of grade 1 acute GVHD. This trial is registered with ClinicalTrials.gov, number NCT00726375.

Original languageEnglish (US)
Pages (from-to)1426-1434
Number of pages9
JournalBiology of Blood and Marrow Transplantation
Volume20
Issue number9
DOIs
StatePublished - Sep 2014

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Keywords

  • Clinical trial
  • Etanercept
  • Grade 1 acute
  • Graft-versus-host disease
  • Hematopoietic stem cell transplantation

ASJC Scopus subject areas

  • Transplantation
  • Hematology
  • Medicine(all)

Cite this

Gatza, E., Braun, T., Levine, J. E., Ferrara, J. L. M., Zhao, S., Wang, T., Chang, L., Harris, A., Pawarode, A., Kitko, C., Magenau, J. M., Yanik, G. A., Couriel, D. R., Goldstein, S., Connelly, J., Reddy, P., Paczesny, S., & Choi, S. W. (2014). Etanercept plus topical corticosteroids as initial therapy for grade one acute graft-versus-host disease after allogeneic hematopoietic cell transplantation. Biology of Blood and Marrow Transplantation, 20(9), 1426-1434. https://doi.org/10.1016/j.bbmt.2014.05.023