Open AccessInflammatory cytokine inhibition with combination daclizumab and infliximab for steroid-refractory acute GVHD
Author(s) -
Alison Rager,
Noelle V. Frey,
Steven C. Goldstein,
Ran Reshef,
Elizabeth O. Hexner,
Alison W. Loren,
Selina M. Luger,
Alexander E. Perl,
Donald E. Tsai,
Jennifer Davis,
Michael Vozniak,
Jacqueline Smith,
Edward A. Stadtmauer,
David Porter
Publication year - 2010
Publication title -
bone marrow transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.609
H-Index - 127
eISSN - 1476-5365
pISSN - 0268-3369
DOI - 10.1038/bmt.2010.117
Subject(s) - daclizumab , medicine , infliximab , gastroenterology , refractory (planetary science) , surgery , transplantation , tumor necrosis factor alpha , tacrolimus , physics , astrobiology
Treatment options for steroid-refractory GVHD (SR-GVHD) are unsatisfactory and prognosis is poor. Inflammatory cytokines IL-2 and TNF-α are important mediators of GVHD and may be critical targets for therapy. We retrospectively reviewed our experience using combination anti-cytokine therapy of daclizumab and infliximab. Seventeen evaluable patients had a median age of 47 years (range 35-63). The conditioning regimen was myeloablative in 13 and non-myeloablative in 4 cases. GVHD occurred at a median of 49 days after transplant in 12 patients (range 21-231 days) and at a median of 46 days (range 25-119 days) after donor lymphocyte infusion in 5 patients. All patients had persistent or progressive GVHD despite 1-2 mg/kg/day of corticosteroids for a median of 7 days (range 2-26 days). They received a combination of daclizumab and infliximab for acute GVHD IBMTR severity index B (3), C (10) or D (4). Of the 17 patients analyzed, 47% responded to treatment, 24% had complete resolution of symptoms and 24% had partial responses. Survival was limited and all the patients died a median of 6.7 months (range 1.6-26) from transplant and 35 days from initiation of daclizumab/infliximab. This retrospective analysis suggests that combination anti-cytokine therapy with daclizumab/infliximab has significant activity in SR-GVHD, but outcomes remain poor. New methods to prevent and treat GVHD are urgently needed.