Haploidentical Stem Cell Transplantation With a Novel Conditioning Regimen in Older Patients: A Prospective Single-Arm Phase 2 Study

Yu-Qian Sun, Ting-Ting Han, Yu Wang, Chen-Hua Yan, Feng-Rong Wang, Zhi-Dong Wang, Jun Kong, Yu-Hong Chen, Huan Chen, Wei Han, Yao Chen, Yuan-Yuan Zhang, Xiao-Hui Zhang, Lan-Ping Xu, Kai-Yan Liu, Xiao-Jun Huang, Yu-Qian Sun, Ting-Ting Han, Yu Wang, Chen-Hua Yan, Feng-Rong Wang, Zhi-Dong Wang, Jun Kong, Yu-Hong Chen, Huan Chen, Wei Han, Yao Chen, Yuan-Yuan Zhang, Xiao-Hui Zhang, Lan-Ping Xu, Kai-Yan Liu, Xiao-Jun Huang

Abstract

Objective: Haploidentical stem cell transplantation (haplo-SCT) has demonstrated encouraging results in younger patients. There is also an increasing need for haplo-SCT in older patients. However, the high risk of treatment-related mortality (TRM) in older patients is still a major concern. We aimed to investigate a novel conditioning regimen (Bu/Flu/Cy/ATG) followed by haplo-SCT in older patients. Method: This prospective, single-arm clinical trial was performed at Peking University Institute of Hematology, China. Patients were enrolled if they were (1) diagnosed with acute leukemia or MDS; (2) without MSD and MUD, and with HID available; and (3) age ≥55 years. The Bu/Flu/Cy/ATG regimen consisted of the following agents: Ara-C (2 g/m2/day, injected i.v.) on days-10 and-9; BU (9.6 mg/kg, injected i.v. in 12 doses) on days-8,-7, and-6; Flu (30 mg/m2/day, injected i.v.) from day-6 to day-2; Cy (1 g/m2/day, injected i.v.) on days-5 and-4; semustine (250 mg/m2, orally) on day-3 and antithymocyte globulin (ATG) [2.5 mg/kg/day, rabbit, SangStat (Lyon, France)] on days-5,-4,-3, and-2. The primary endpoint was 1-year TRM. Results: From April 1, 2018 to April 10, 2020, a total of 50 patients were enrolled. All patients achieved neutrophil engraftment with complete donor chimerism. The cumulative incidence of grade 2-4 aGVHD at day-100 was 22.0%. The cumulative incidences of CMV viremia and EBV viremia on day 100 were 68.0 and 20.0%, respectively. The cumulative incidence of TRM at 1-year was 23.3%. and the cumulative incidence of relapse (CIR) at 1 year after transplantation was 16.5%. The overall survival (OS) and leukemia-free survival (LFS) at 1 year were 63.5 and 60.2%, respectively. The outcomes were also comparable with patients who received Bu/Cy/ATG regimen using a propensity score matching method. Conclusions: In conclusion, this study suggested that a novel conditioning regimen followed by haploidentical HSCT might be a promising option for older patients. The study was registered as a clinical trial. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT03412409.

Keywords: anti-thymocyte globulin; cyclophosphamide; elderly; fludarabine; haploidentical transplant.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2021 Sun, Han, Wang, Yan, Wang, Wang, Kong, Chen, Chen, Han, Chen, Zhang, Zhang, Xu, Liu and Huang.

Figures

Figure 1
Figure 1
GVHD. (A) Acute GVHD grade 2-4; (B) Acute GVHD grade 3-4; (C) Chronic GVHD; (D) extensive chronic GVHD.
Figure 2
Figure 2
Virus infection (A) CMV; (B) EBV.
Figure 3
Figure 3
Outcomes (A) TRM; (B) CIR; (C) OS; (D) DFS.

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