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Biol Blood Marrow Transplant. 2014 Sep;20(9):1426-34. doi: 10.1016/j.bbmt.2014.05.023. Epub 2014 Jun 2.

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

Author information

1
Blood and Marrow Transplantation Program, University of Michigan, Ann Arbor, Michigan; Department of Pediatrics, University of Michigan, Ann Arbor, Michigan.
2
Department of Biostatistics, University of Michigan, Ann Arbor, Michigan.
3
Blood and Marrow Transplantation Program, University of Michigan, Ann Arbor, Michigan; Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan.
4
Department of Pediatrics, Indiana University, Indianapolis, Indiana.
5
Blood and Marrow Transplantation Program, University of Michigan, Ann Arbor, Michigan; Department of Pediatrics, University of Michigan, Ann Arbor, Michigan. Electronic address: sungchoi@med.umich.edu.

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 28 days. Study patients (n = 34) had a median age of 51 years (range, 10 to 67 years) and had undergone unrelated (n = 22) or related (n = 12) donor HSCT. Study patients were treated with etanercept (.4 mg/kg, maximum 25 mg/dose) twice weekly for 4 to 8 weeks. Ten of 34 patients (29%) progressed to grade 2 to 4 acute GVHD within 28 days. The cumulative incidence of grade 2 to 4 and grade 3 to 4 acute GVHD at 1 year was 41% and 3%, respectively. Nonrelapse mortality was 19% and overall survival was 63% at 2 years. 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 28 days, 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) 28 days 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.

KEYWORDS:

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

PMID:
24892263
PMCID:
PMC4145722
DOI:
10.1016/j.bbmt.2014.05.023
[Indexed for MEDLINE]
Free PMC Article

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