Randomized phase II trial comparing two dose levels of thymoglobulin in patients undergoing unrelated donor hematopoietic cell transplant.
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.
Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas M. D. AndersonCancer Center, Houston, TX, USA. qbashir@mdanderson.org
Qaiser
Q
Bashir
Mark F
MF
Munsell
Sergio
S
Giralt
Leandro
L
de Padua Silva
Manish
M
Sharma
Daniel
D
Couriel
Alexandre
A
Chiattone
Uday
U
Popat
Muzaffar H
MH
Qazilbash
Marcelo
M
Fernandez-Vina
Richard E
RE
Champlin
Marcos J
MJ
de Lima
D000328:Adult; D000368:Aged; D000961:Antilymphocyte Serum / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000517:prevention & control; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012074:Remission Induction; D015996:Survival Rate; D019172:Transplantation Conditioning / Q000379:methods; D016896:Treatment Outcome
D000961:Antilymphocyte Serum; C512542:thymoglobulin