Reduced Dose of Pre-Transplant Cyclophosphamide in Bu/Cy Conditioning Regimens Promote the Prognosis of Patients With Younger Donors in Haploidentical Hematopoietic Stem Cell Transplantation for Aplastic Anemia

Jing Li; Shijia Li; Xiya Wei; Shiyuan Zhou; Wenjuan Zhu; Qian Zhu; Chao Ma; Xiao Ma; Depei Wu; Xiaojin Wu

doi:10.1016/j.transproceed.2026.05.013

Reduced Dose of Pre-Transplant Cyclophosphamide in Bu/Cy Conditioning Regimens Promote the Prognosis of Patients With Younger Donors in Haploidentical Hematopoietic Stem Cell Transplantation for Aplastic Anemia

Transplant Proc. 2026 Jun 9:S0041-1345(26)00267-8. doi: 10.1016/j.transproceed.2026.05.013. Online ahead of print.

Authors

Jing Li¹, Shijia Li¹, Xiya Wei¹, Shiyuan Zhou¹, Wenjuan Zhu¹, Qian Zhu², Chao Ma², Xiao Ma¹, Depei Wu¹, Xiaojin Wu³

Affiliations

¹ Department of Hematopathology, National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China; The First Affiliated Hospital of Soochow University, Suzhou, China Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China.
² Soochow Hopes Hematonosis Hospital, Suzhou, China.
³ Department of Hematopathology, National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China; The First Affiliated Hospital of Soochow University, Suzhou, China Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China. Electronic address: wuxiaojin@suda.edu.cn.

PMID: 42265036
DOI: 10.1016/j.transproceed.2026.05.013

Abstract

Objective: The establishment of an optimal preparative regimen for haploidentical hematopoietic stem cell transplantation (haplo-HSCT) in patients with aplastic anemia remains a matter of investigation. This study aimed to assess whether reducing the total dose of cyclophosphamide to 160 mg/kg could decrease toxicity while maintaining engraftment and achieving survival rates comparable to or better than those observed with the conventional Bu/Cy regimen using a cyclophosphamide dose of 200 mg/kg for haplo-HSCT.

Methods: A retrospective analysis was conducted on 157 patients who underwent myeloablative haplo-HSCT with a Bu/Cy-based conditioning regimen for aplastic anemia. Of the 157 patients, the median age of the recipients was 29 years (range: 7-56), and the median age of the donors was 40 years (range: 9-63). The patients were divided into 2 groups based on the dose of cyclophosphamide in the conditioning regimen: the Cy 160mg group (n = 41, 160 mg/kg) and the Cy 200mg group (n = 116, 200 mg/kg). Subsequent analyses were conducted on patients who were separately divided into 2 groups , using the median age of the donors, 40 years ,as the cutoff.

Results: In the overall cohort, there were no significant differences in 1-year overall survival (OS) and 1-year failure-free survival (FFS) between patients transplanted from the Cy 160 mg group and the Cy 200mg group (p = .32 and p = .55, respectively), despite the Cy 160mg group exhibited significantly delayed neutrophil engraftment compared to the Cy 200mg group (p = .043). What's more, when selecting donors below the age of 40, patients in the Cy 160mg group showed a lower rate of TRM (p = .046) and a higher rate of OS and FFS compared to those in the Cy 200mg group (p = .027 and p = .027, respectively), although when donors were above 40 years of age, the cumulative incidence of graft failure was higher in the Cy 160mg group compared to the Cy 200mg group in these people (p = .012). As for transplant-related complications, such as infections, GVHD and TMA, no significance were found between the Cy 160mg group and Cy 200mg group mainly, furthermore, the Cy 160mg group had a trend to a lower incidence of severe cardiotoxicity, despite the difference was still not statistically significant (0% vs. 6.1%, p = .11).

Conclusion: Our results suggest that a reduced dose of cyclophosphamide in the Bu/Cy conditioning regimen should be selected for AA patients to obtain a better prognosis when donors are younger than 40 years.