Treatment of Steroid-Resistant Acute Graft-Versus-Host Disease with Rabbit Antithymocyte Globulin
| Autor: | E. A. Conneally, Thomas J. Nevill, Shepherd Jd, Cynthia L. Toze, Donna E. Hogge, Michael J. Barnett, C J Currie, K G McCaul, Hans G. Klingemann, Heather J. Sutherland, Nantel Sh |
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| Rok vydání: | 2000 |
| Předmět: |
Adult
Male medicine.medical_specialty Fever medicine.drug_class Opportunistic infection T-Lymphocytes Immunology Drug Resistance Graft vs Host Disease Salvage therapy Infections Gastroenterology Adrenal Cortex Hormones Internal medicine Animals Humans Transplantation Homologous Medicine Survival rate Antilymphocyte Serum Salvage Therapy Leukopenia Thymoglobulin business.industry Remission Induction Hematopoietic Stem Cell Transplantation Hematology Middle Aged medicine.disease Lymphoproliferative Disorders Surgery Survival Rate Transplantation Treatment Outcome Acute Disease Corticosteroid Female Rabbits medicine.symptom business Complication |
| Zdroj: | Journal of Hematotherapy & Stem Cell Research. 9:367-374 |
| ISSN: | 1525-8165 |
| DOI: | 10.1089/15258160050079470 |
| Popis: | Acute graft-versus-host disease (A-GVHD) is a life-threatening complication of allogeneic stem cell transplantation (SCT), and primary therapy consists of high-dose corticosteroids. Patients who fail to respond adequately to corticosteroids require salvage treatment, with anti-T cell antibodies being the most commonly utilized group of agents. We report our institution's experience treating steroid-resistant GVHD in 36 adult patients (median age 39 years, range 24-55) with a rabbit antithymocyte globulin product (thymoglobulin). Eleven patients had undergone sibling SCT (10 histocompatible, 1 one-antigen mismatched) and 25 patients had received unrelated donor bone marrow (17 matched, 8 one-antigen mismatched); 32 patients (89%) had grade III or IV A-GVHD. Thymoglobulin was administered in two different regimens; group 1 patients (n = 13) received 2.5 mg/kg/day x 4-6 consecutive days with maintenance of all other immunosuppressives. Group 2 patients (n = 21) were given the same dose of thymoglobulin on days 1, 3, 5, and 7 with discontinuation of cyclosporine for 14 days, during which the corticosteroid dose was held at 2-3 mg/kg/day. Two patients had severe adverse reactions to thymoglobulin (hypoxemia and hypotension) and could not complete treatment, however, in the other patients, aside from transient leukopenia (25%) and and hepatic dysfunction (25%), the antibody preparation was well tolerated. Of the 34 evaluable patients, 13 patients had a complete response (38%) and 7 patients (21%) had a partial response, for an overall response rate of 59%. Response rate was higher in group 1 patients (77%) compared to group 2 patients (48%), (p = 0.15); skin GVHD was more responsive (96% of patients) than gut GVHD (46% of patients) or hepatic GHVD (36% of patients). Opportunistic infections were a significant complication, with 11 patients developing systemic fungal infections and 9 patients serious viral infections; there were seven episodes of bacteremia following thymoglobulin treatment and one fatal protozoal infection. There were 9 patients (25%) who developed post-SCT lymphoproliferative disorder (PTLD) and 4 patients who had a relapse of underlying primary malignancy; none of these patients survived. Of the 36 patients entered on the study, only 2 patients (6%) survive, at 15+ and 34+ months post-unrelated donor SCT. Although thymoglobulin is associated with an impressive response rate when administered for advanced steroid-resistant GVHD, long-term survival is uncommon, even in responders, primarily due to the high risk of developing either an opportunistic infection or a PTLD. |
| Databáze: | OpenAIRE |
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