title: Inflammatory cytokine inhibition with combination daclizumab and infliximab for steroid-refractory acute GVHD.
abstract: 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.
authors.affiliation: Division of Hematology-Oncology, Blood and Marrow Transplant Program, University of Pennsylvania Medical Center, Philadelphia, PA 19104, USA. alison.rager@uphs.upenn.edu
authors.forename: A
authors.initials: A
authors.lastname: Rager
authors.forename: N
authors.initials: N
authors.lastname: Frey
authors.forename: S C
authors.initials: SC
authors.lastname: Goldstein
authors.forename: R
authors.initials: R
authors.lastname: Reshef
authors.forename: E O
authors.initials: EO
authors.lastname: Hexner
authors.forename: A
authors.initials: A
authors.lastname: Loren
authors.forename: S M
authors.initials: SM
authors.lastname: Luger
authors.forename: A
authors.initials: A
authors.lastname: Perl
authors.forename: D
authors.initials: D
authors.lastname: Tsai
authors.forename: J
authors.initials: J
authors.lastname: Davis
authors.forename: M
authors.initials: M
authors.lastname: Vozniak
authors.forename: J
authors.initials: J
authors.lastname: Smith
authors.forename: E A
authors.initials: EA
authors.lastname: Stadtmauer
authors.forename: D L
authors.initials: DL
authors.lastname: Porter
mesh_terms: D000208:Acute Disease; D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000077561:Daclizumab; D004351:Drug Resistance; D005260:Female; D006086:Graft vs Host Disease / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D000069285:Infliximab; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012189:Retrospective Studies; D013256:Steroids / Q000494:pharmacology; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D013256:Steroids; D000069285:Infliximab; D000077561:Daclizumab