TY - JOUR
T1 - Randomized phase II trial comparing two dose levels of thymoglobulin in patients undergoing unrelated donor hematopoietic cell transplant
AU - Bashir, Qaiser
AU - Munsell, Mark F.
AU - Giralt, Sergio
AU - De Padua Silva, Leandro
AU - Sharma, Manish
AU - Couriel, Daniel
AU - Chiattone, Alexandre
AU - Popat, Uday
AU - Qazilbash, Muzaffar H.
AU - Fernandez-Vina, Marcelo
AU - Champlin, Richard E.
AU - De Lima, Marcos J.
N1 - Funding Information:
This work was supported in part by the NCI Cancer Center Support Grant to The University of Texas M. D. Anderson Cancer Center (P30 CA016672).
PY - 2012/5
Y1 - 2012/5
N2 - The optimal dose and schedule of thymoglobulin (ATG) for graft-versus-host disease prevention (GVHD) is unknown. We compared two doses of ATG (4.5 mg/kg and 7.5 mg/kg) in a Bayesian adaptively randomized fashion, and assessed whether ATG levels measured on days 0, 7, 14 and 28 were associated with clinical outcomes. Treatment success was defined as the patient being alive, engrafted, in remission and without acute GVHD at day 100. Twenty patients received ATG 4.5 mg/kg (n = 15) or 7.5 mg/kg (n = 5) with reduced-intensity conditioning followed by unrelated donor hematopoietic cell transplant. The first 10 patients were fairly randomized, but the next 10 patients were adaptively randomized to the arm with higher success rate (4.5 mg/kg arm in this trial). The posterior mean treatment success rates for the ATG 4.5 mg/kg and ATG 7.5 mg/kg arms were 0.73 and 0.45, respectively. The posterior probability that the success rate was greater in the 4.5 mg/kg arm than in the 7.5 mg/kg arm was 0.93. There was no difference in the overall survival (p = 0.607), relapse-free survival (p = 0.607), treatment-related mortality (p = 0.131) or incidence of acute (p = 0.303) or chronic GVHD (p = 0.999) between the two doses. ATG levels were not associated with clinical outcomes. Thus, our results favor the use of ATG 4.5 mg/kg over ATG 7.5 mg/kg in patients undergoing unrelated donor hematopoietic cell transplant with reduced-intensity conditioning regimens.
AB - The optimal dose and schedule of thymoglobulin (ATG) for graft-versus-host disease prevention (GVHD) is unknown. We compared two doses of ATG (4.5 mg/kg and 7.5 mg/kg) in a Bayesian adaptively randomized fashion, and assessed whether ATG levels measured on days 0, 7, 14 and 28 were associated with clinical outcomes. Treatment success was defined as the patient being alive, engrafted, in remission and without acute GVHD at day 100. Twenty patients received ATG 4.5 mg/kg (n = 15) or 7.5 mg/kg (n = 5) with reduced-intensity conditioning followed by unrelated donor hematopoietic cell transplant. The first 10 patients were fairly randomized, but the next 10 patients were adaptively randomized to the arm with higher success rate (4.5 mg/kg arm in this trial). The posterior mean treatment success rates for the ATG 4.5 mg/kg and ATG 7.5 mg/kg arms were 0.73 and 0.45, respectively. The posterior probability that the success rate was greater in the 4.5 mg/kg arm than in the 7.5 mg/kg arm was 0.93. There was no difference in the overall survival (p = 0.607), relapse-free survival (p = 0.607), treatment-related mortality (p = 0.131) or incidence of acute (p = 0.303) or chronic GVHD (p = 0.999) between the two doses. ATG levels were not associated with clinical outcomes. Thus, our results favor the use of ATG 4.5 mg/kg over ATG 7.5 mg/kg in patients undergoing unrelated donor hematopoietic cell transplant with reduced-intensity conditioning regimens.
KW - ATG
KW - graft-versus-host disease
KW - hematopoietic cell transplant
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U2 - 10.3109/10428194.2011.634039
DO - 10.3109/10428194.2011.634039
M3 - Article
C2 - 22023525
AN - SCOPUS:84860009428
SN - 1042-8194
VL - 53
SP - 915
EP - 919
JO - Leukemia and Lymphoma
JF - Leukemia and Lymphoma
IS - 5
ER -