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: Ying-Jun Chang, Yu Wang, Xiao-Dong Mo, Xiao-Hui Zhang, Lan-Ping Xu, Chen-Hua Yan, Huan Chen, Yu-Hong Chen, Yao Chen, Wei Han, Feng-Rong Wang, Jing-Zhi Wang, Kai-Yan Liu, Xiao-Jun Huang
• Journal: Cancer (Cancer) Vol. 123 Issue 15 Pg. 2881-2892 (Aug 01 2017) ISSN: 1097-0142 [Electronic] United States
• PMID: 28301690 (Publication Type: Journal Article, Randomized Controlled Trial)
• Copyright: © 2017 American Cancer Society.

Chemical References

• Antilymphocyte Serum
• Immunologic Factors
• thymoglobulin

Topics

• Adolescent
• Adult
• Antilymphocyte Serum (administration & dosage)
• Disease-Free Survival
• Female
• Follow-Up Studies
• Graft vs Host Disease (prevention & control)
• Hematopoietic Stem Cell Transplantation (methods)
• Humans
• Immunologic Factors (administration & dosage)
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive (therapy)
• Leukemia, Myeloid, Acute (therapy)
• Male
• Middle Aged
• Myelodysplastic Syndromes (therapy)
• Precursor Cell Lymphoblastic Leukemia-Lymphoma (therapy)
• Transplantation Conditioning (methods)
• Young Adult