title: Combination therapy with tacrolimus and anti-thymocyte globulin for the treatment of steroid-resistant acute graft-versus-host disease developing during cyclosporine prophylaxis.
abstract: We report our experience with the combination of anti-thymocyte globulin (ATGAM) and tacrolimus in the treatment of 20 patients with steroid refractory and dependent acute graft-versus-host disease (GVHD) transplanted between August 1996 and February 2000. All patients received cyclosporine-based GVHD prophylaxis. Thirteen patients developed a maximum of grade IV, five grade III and two grade II acute GVHD, with 15 patients being refractory to steroids and five dependent on steroids. Patients were treated with ATGAM (15 mg/kg for 5 d) and tacrolimus (0.025--0.1 mg/kg/d) in addition to continuation of their high-dose steroids and cessation of their cyclosporine. Within 28 d of treatment, we observed eight complete responses (CR), six partial responses (PR) and six with no response. Overall response (CR + PR) was predicted by GVHD severity. Infectious complications occurred in 80% of patients. The median survival was 86.5 d (range, 21--1081 d) with 35% of patients remaining alive. Survival following combination therapy was significantly more likely in men (P < 0.001), skin-only GVHD (P = 0.027), less severe GVHD (P = 0.048), and in responders to tacrolimus and ATGAM (P < 0.001). In conclusion, concurrent introduction of ATGAM and tacrolimus is a promising therapeutic combination for GVHD refractory to steroids and cyclosporine.
authors.affiliation: Bone Marrow Transplant Unit, Royal Brisbane Hospital, Brisbane, Australia. durrants@health.qld.gov.au
authors.forename: P
authors.initials: P
authors.lastname: Mollee
authors.forename: A J
authors.initials: AJ
authors.lastname: Morton
authors.forename: I
authors.initials: I
authors.lastname: Irving
authors.forename: S
authors.initials: S
authors.lastname: Durrant
mesh_terms: D000208:Acute Disease; D000328:Adult; D016572:Cyclosporine / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D006086:Graft vs Host Disease / Q000188:drug therapy* / Q000517:prevention & control; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007518:Isoantibodies / Q000627:therapeutic use*; D007938:Leukemia / Q000188:drug therapy / Q000601:surgery*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000601:surgery; D008223:Lymphoma / Q000188:drug therapy / Q000601:surgery; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy / Q000601:surgery; D009190:Myelodysplastic Syndromes / Q000188:drug therapy / Q000601:surgery; D016559:Tacrolimus / Q000627:therapeutic use*; D014184:Transplantation, Homologous
chemical_list: D007166:Immunosuppressive Agents; D007518:Isoantibodies; C035678:anti-Thy antibody; D016572:Cyclosporine; D016559:Tacrolimus; D008727:Methotrexate