title: Optimal dose of rabbit thymoglobulin in conditioning regimens for unmanipulated, haploidentical, hematopoietic stem cell transplantation: Long-term outcomes of a prospective randomized trial.
abstract: BACKGROUND
  Antithymocyte globulin (ATG) is an important component of conditioning regimens to prevent severe graft-versus-host disease (GVHD) in patients undergoing unmanipulated, haploidentical stem cell transplantation (haplo-SCT). However, to the authors' knowledge, the optimal dose of ATG is unknown.
  
  
  METHODS
  In this prospective, randomized trial, the authors compared the long-term outcomes of 2 ATG doses (rabbit thymoglobulin) used in myeloablative conditioning before unmanipulated haplo-HSCT. Patients were randomly assigned (1:1) to received 10 mg/kg (ATG-10) or 6 mg/kg (ATG-6) of ATG. Analysis of disease-free survival, GVHD-free/recurrence-free survival (GRFS), disease recurrence, nonrecurrence mortality, and chronic GVHD (cGVHD) included the entire population. Late effects were assessed in disease-free patients who had survived for at least 6 months and had received regular follow-up evaluations.
  
  
  RESULTS
  A total of 224 patients were recruited. The median follow-up period was 1614 days (range, 28-1929 days). The rate of infection-related deaths in ATG-10 arm was double that of the ATG-6 arm (14.3% vs 7.1%; P = .084). The 5-year cumulative incidence was comparable between the ATG-6 and ATG-10 groups for disease recurrence (12.8% vs 13.4%; P = .832) and nonrecurrence mortality (11.6% vs 17.0%; P = .263). The 5-year probability of disease-free survival was comparable between the groups (75.6% vs 69.6%; P = .283). The 5-year cumulative incidence of cGVHD was found to be higher with ATG-6 (75.0% vs 56.3% [P = .007] and moderate-to-severe cGVHD: 56.3% vs 30.4% [P<.0001]) as well as that for late effects (71.2% vs 56.9%; P = .043). The 5-year probability of GRFS was higher in the ATG-10 group (41.0% vs 26.8%; P = .008). In the multivariate analysis, ATG-10 was found to be associated with a lower risk of cGVHD and improved GRFS.
  
  
  CONCLUSIONS
  ATG-10 was found to be associated with better GVHD prevention and superior GRFS, but an increase in infection-related deaths. Cancer 2017;123:2881-92. © 2017 American Cancer Society.
authors.affiliation: Peking University People's Hospital, Peking University Institute of Hematology, Beijing, China.
authors.forename: Ying-Jun
authors.initials: YJ
authors.lastname: Chang
authors.affiliation: Peking University People's Hospital, Peking University Institute of Hematology, Beijing, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Peking University People's Hospital, Peking University Institute of Hematology, Beijing, China.
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Mo
authors.affiliation: Peking University People's Hospital, Peking University Institute of Hematology, Beijing, China.
authors.forename: Xiao-Hui
authors.initials: XH
authors.lastname: Zhang
authors.affiliation: Peking University People's Hospital, Peking University Institute of Hematology, Beijing, China.
authors.forename: Lan-Ping
authors.initials: LP
authors.lastname: Xu
authors.affiliation: Peking University People's Hospital, Peking University Institute of Hematology, Beijing, China.
authors.forename: Chen-Hua
authors.initials: CH
authors.lastname: Yan
authors.affiliation: Peking University People's Hospital, Peking University Institute of Hematology, Beijing, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Chen
authors.affiliation: Peking University People's Hospital, Peking University Institute of Hematology, Beijing, China.
authors.forename: Yu-Hong
authors.initials: YH
authors.lastname: Chen
authors.affiliation: Peking University People's Hospital, Peking University Institute of Hematology, Beijing, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Peking University People's Hospital, Peking University Institute of Hematology, Beijing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Han
authors.affiliation: Peking University People's Hospital, Peking University Institute of Hematology, Beijing, China.
authors.forename: Feng-Rong
authors.initials: FR
authors.lastname: Wang
authors.affiliation: Peking University People's Hospital, Peking University Institute of Hematology, Beijing, China.
authors.forename: Jing-Zhi
authors.initials: JZ
authors.lastname: Wang
authors.affiliation: Peking University People's Hospital, Peking University Institute of Hematology, Beijing, China.
authors.forename: Kai-Yan
authors.initials: KY
authors.lastname: Liu
authors.affiliation: Peking University People's Hospital, Peking University Institute of Hematology, Beijing, China.|Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China.|Peking-Tsinghua Center for Life Sciences, Beijing, China.
authors.forename: Xiao-Jun
authors.initials: XJ
authors.lastname: Huang
mesh_terms: D000293:Adolescent; D000328:Adult; D000961:Antilymphocyte Serum / Q000008:administration & dosage*; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006086:Graft vs Host Disease / Q000517:prevention & control*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000628:therapy*; D015470:Leukemia, Myeloid, Acute / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000628:therapy*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000628:therapy*; D019172:Transplantation Conditioning / Q000379:methods*; D055815:Young Adult
chemical_list: D000961:Antilymphocyte Serum; D007155:Immunologic Factors; C512542:thymoglobulin
keywords: antithymocyte globulin; chronic graft-versus-host disease (cGVHD); graft-versus-host disease-free/recurrence-free survival; haploidentical; hematopoietic stem cell transplantation; late effects