Treatment of human acute graft-versus-host disease with antithymocyte globulin and cyclosporine with or without methylprednisolone.
Forty-eight patients with hematologic malignancies treated by allogeneic marrow transplantation developed acute graft-versus-host disease (GVHD), grades II-IV, despite prophylaxis with methotrexate. They were treated with a combination of antithymocyte globulin (ATG) and cyclosporine (CsA), with or without the addition of methylprednisolone (MP). Thirty patients had received HLA-identical and 18 HLA-nonidentical transplants. Median onset of GVHD was day 13 (range 8-60) for patients with HLA-nonidentical grafts and day 18 (range 7-48) for patients given HLA-identical grafts (P = 0.01). Forty-five patients could be evaluated for response on day 7 of therapy. Among these, 13 of 27 given ATG/CSP and 6 of 18 given ATG/CSP/MP improved. Among 33 patients evaluable on day 14 of therapy 13 of 19 given ATG/CSP and 5 of 14 given ATG/CSP/MP showed improvement of GVHD. Patients given HLA-nonidentical grafts responded somewhat (although not significantly) less frequently than patients given HLA-identical grafts. Chronic GVHD developed in 16 of 18 evaluable patients given ATG/CSP and in 5 of 6 given ATG/CSP/MP. Viral, bacterial, and fungal infections were the major cause of death in both groups. Interstitial pneumonitis was more frequent among patients given ATG/CSP/MP. Survival beyond 6 months was 67% among patients treated with ATG/CSP and 25% with ATG/CSP/MP. These data indicate that a regimen of ATG/CSP is of value in the treatment of acute GVHD. The addition of MP was not beneficial and resulted in decreased survival--presumably because of excessive immunosuppression and associated complications.
D000293:Adolescent; D000328:Adult; D000961:Antilymphocyte Serum / Q000008:administration & dosage* / Q000009:adverse effects; D016026:Bone Marrow Transplantation; D002986:Clinical Trials as Topic; D003524:Cyclosporins / Q000008:administration & dosage* / Q000009:adverse effects; D004359:Drug Therapy, Combination; D005260:Female; D006086:Graft vs Host Disease / Q000628:therapy*; D006801:Humans; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage* / Q000009:adverse effects; D011658:Pulmonary Fibrosis / Q000209:etiology
D000961:Antilymphocyte Serum; D003524:Cyclosporins; D008775:Methylprednisolone