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.
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: Mikael Sundin; A John Barrett; Olle Ringdén; Mehmet Uzunel; Helena Lönnies; Asa-Lena Dackland; Birger Christensson; Katarina Le Blanc Journal: J Immunother Date: 2009-09 Impact factor: 4.456
Authors: A B M Lim; J Storek; A Beligaswatte; M Collins; M Tacey; T Williamson; K Mason; E Li; M A Chaudhry; J A Russell; A Daly; J Szer; I Lewis; D Ritchie Journal: Bone Marrow Transplant Date: 2015-02-02 Impact factor: 5.483
Authors: Johan Törlén; Olle Ringdén; Karin Garming-Legert; Per Ljungman; Jacek Winiarski; Kari Remes; Maija Itälä-Remes; Mats Remberger; Jonas Mattsson Journal: Haematologica Date: 2016-08-04 Impact factor: 9.941
Authors: Olle Ringdén; Steven Z Pavletic; Claudio Anasetti; A John Barrett; Tao Wang; Dan Wang; Joseph H Antin; Paolo Di Bartolomeo; Brian J Bolwell; Christopher Bredeson; Mitchell S Cairo; Robert P Gale; Vikas Gupta; Theresa Hahn; Gregory A Hale; Jorg Halter; Madan Jagasia; Mark R Litzow; Franco Locatelli; David I Marks; Philip L McCarthy; Morton J Cowan; Effie W Petersdorf; James A Russell; Gary J Schiller; Harry Schouten; Stephen Spellman; Leo F Verdonck; John R Wingard; Mary M Horowitz; Mukta Arora Journal: Blood Date: 2008-12-04 Impact factor: 22.113