Dose study of thymoglobulin during conditioning for unrelated donor allogeneic stem-cell transplantation.

Abstract

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.

METHOD:

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.

CONCLUSION:

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.

• Authors: Mats Remberger, Britt-Marie Svahn, Jonas Mattsson, Olle Ringdén
• Journal: Transplantation (Transplantation) Vol. 78 Issue 1 Pg. 122-7 (Jul 15 2004) ISSN: 0041-1337 [Print] United States
• PMID: 15257050 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antilymphocyte Serum

Topics

• Adolescent
• Adult
• Antilymphocyte Serum (administration & dosage)
• Bacterial Infections (mortality, prevention & control)
• Child
• Child, Preschool
• Female
• Graft vs Host Disease (mortality, prevention & control)
• Hematopoietic Stem Cell Transplantation (mortality)
• Humans
• Infant
• Infant, Newborn
• Male
• Middle Aged
• Recurrence
• Retrospective Studies
• Risk Factors
• Survival Analysis
• T-Lymphocytes (immunology)
• Tissue Donors
• Transplantation Conditioning (methods)