title: Combination antithymocyte globulin and soluble TNFalpha inhibitor (etanercept) +/- mycophenolate mofetil for treatment of steroid refractory acute graft-versus-host disease.
abstract: Antitumor necrosis factor-alpha antibodies are increasingly being used for the treatment of steroid-refractory acute graft-versus-host disease (GVHD) complicating allogeneic stem cell transplantation. We retrospectively reviewed the outcomes of 16 patients with refractory acute predominantly visceral GVHD treated with combination antithymocyte globulin (ATG), tacrolimus and etanercept +/- mycophenolate mofetil (MMF) at our institution. Overall response rate (CR+PR) was 81%, with median survival post commencing salvage immunosuppression 224 days (range 20-1216 days). In total, eight patients (50%) died, including from progressive GVHD in two cases (13%), infection in five (31%) and relapse of underlying malignancy in one (6%). In comparison to our previous experience of ATG+tacrolimus as treatment for refractory visceral GVHD, both response rate and overall survival were improved with addition of etanercept, with no apparent increase in infectious complications. As such, use of etanercept in combination with ATG +/- MMF for treatment of steroid refractory acute GVHD appears to be associated with high response rates, significant survival and no unexpected toxicity. Further study of this immunosuppression combination in a larger cohort of patients in this setting is indicated.
authors.affiliation: Department of Haematology, Royal Brisbane and Women's Hospital, Brisbane, Queensland 4029, Australia. glen_kennedy@health.qld.gov.au
authors.forename: G A
authors.initials: GA
authors.lastname: Kennedy
authors.forename: J
authors.initials: J
authors.lastname: Butler
authors.forename: R
authors.initials: R
authors.lastname: Western
authors.forename: J
authors.initials: J
authors.lastname: Morton
authors.forename: S
authors.initials: S
authors.lastname: Durrant
authors.forename: G R
authors.initials: GR
authors.lastname: Hill
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage; D000961:Antilymphocyte Serum / Q000008:administration & dosage*; D018572:Disease-Free Survival; D004351:Drug Resistance / Q000187:drug effects; D004359:Drug Therapy, Combination; D000068800:Etanercept; D005260:Female; D006086:Graft vs Host Disease / Q000188:drug therapy* / Q000209:etiology / Q000401:mortality; D006801:Humans; D007074:Immunoglobulin G / Q000008:administration & dosage*; D007165:Immunosuppression Therapy / Q000379:methods; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D007239:Infections / Q000209:etiology / Q000473:pathology; D008232:Lymphoproliferative Disorders / Q000150:complications / Q000401:mortality / Q000628:therapy; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives*; D018124:Receptors, Tumor Necrosis Factor / Q000008:administration & dosage*; D012008:Recurrence; D012189:Retrospective Studies; D016879:Salvage Therapy
chemical_list: D000893:Anti-Inflammatory Agents; D000961:Antilymphocyte Serum; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D018124:Receptors, Tumor Necrosis Factor; D009173:Mycophenolic Acid; D000068800:Etanercept; D008775:Methylprednisolone