Combination therapy with tacrolimus and anti-thymocyte globulin for the treatment of steroid-resistant acute graft-versus-host disease developing during cyclosporine prophylaxis

We report our experience with the combination of anti-thymocyte globulin (A TGAM) and tacrolimus in the treatment of 20 patients with steroid refractor y and dependent acute graft-versus-host disease (GVHD) transplanted between August 1996 and February 2000. All patients received cyclosporine-based GV HD prophylaxis. Thirteen patients developed a maximum of grade TV, five gra de III and two grade II acute GVHD, with 15 patients being refractory to st eroids 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 continuat ion 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 pre dicted by GVHD severity. Infectious complications occurred in 80% of patien ts. The median survival was 86.5 d (range, 21-1081 d) with 35% of patients remaining alive, Survival following combination therapy was significantly m ore 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 conc lusion, concurrent introduction of ATGAM and tacrolimus is a promising ther apeutic combination for GVHD refractory to steroids and cyclosporine.