• Mats Remberger, Britt-Marie Svahn, Jonas Mattsson, and Olle Ringdén.
• Department of Clinical Immunology, Karolinska Institute, Huddinge University Hospital, Stockholm, Sweden. mats.remberger@labmed.ki.se
• Transplantation. 2004 Jul 15; 78 (1): 122-7.

BackgroundThymoglobulin given before allo-hematopoietic stem-cell transplantation (HSCT) from unrelated donors reduces acute graft-versus-host disease (GvHD), but the optimal dose is unknown.MethodFour different doses of Thymoglobulin were given to 162 patients with hematologic malignancies undergoing unrelated donor HSCT: 4, 6, 8, and 10 mg/kg. Stem-cell source was bone marrow in 102 cases and peripheral blood stem cells in 60. Conditioning was cyclophosphamide combined with total-body irradiation or busulfan. GvHD prophylaxis was cyclosporine and methotrexate.ResultsThe lowest dose of Thymoglobulin significantly increased the risk for acute GvHD II or greater (odds ratio [OR] 2.67, P=0.015) and III or greater (OR 4.12, P=0.03). GvHD-associated deaths were more common in the lowest Thymoglobulin dose (6/51) compared with higher doses (2/111), P<0.01. No difference in bacteremia and cytomegalovirus reactivation was found. A trend for more infectious death (11/55 vs. 11/107, P=0.09) was found in the 10 mg/kg group compared with lower doses. Median dose of Thymoglobulin (6-8 mg/kg) was associated with lower transplant-related mortality (TRM) (hazard ratio [HR] 0.35, P=0.03) and better survival (HR 0.45, P=0.027) in multivariate analysis, whereas no effect on relapse and relapse-free survival was found.ConclusionLow-dose (4 mg/kg) of Thymoglobulin increased the risk for severe acute GvHD, whereas 10 mg/kg increased the risk for infectious death. Median doses (6-8 mg/kg) of Thymoglobulin resulted in the lowest TRM and best survival.

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