Dose study of thymoglobulin during conditioning for unrelated donor allogeneic stem-cell transplantation.
BACKGROUND
Thymoglobulin given before allo-hematopoietic stem-cell transplantation (HSCT) from unrelated donors reduces acute graft-versus-host disease (GvHD), but the optimal dose is unknown.


METHODS
Four 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.


RESULTS
The 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.


CONCLUSIONS
Low-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.
Remberger
Mats
M
Department of Clinical Immunology, Karolinska Institute, Huddinge University Hospital, Stockholm, Sweden. mats.remberger@labmed.ki.se
Svahn
Britt-Marie
BM
Mattsson
Jonas
J
Ringdén
Olle
O
D000293:Adolescent; D000328:Adult; D000961:Antilymphocyte Serum / Q000008:administration & dosage*; D001424:Bacterial Infections / Q000401:mortality / Q000517:prevention & control; D002648:Child; D002675:Child, Preschool; D005260:Female; D006086:Graft vs Host Disease / Q000401:mortality / Q000517:prevention & control; D018380:Hematopoietic Stem Cell Transplantation / Q000401:mortality*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D012189:Retrospective Studies; D012307:Risk Factors; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000276:immunology*; D014019:Tissue Donors; D019172:Transplantation Conditioning / Q000379:methods*
D000961:Antilymphocyte Serum