Mismatched unrelated donors allogeneic hematopoietic stem cell transplantation with antithymocyte globulin for hematological malignancies: a multicenter retrospective study in China

Lin Li; Yi Chen; Ting Chen; Yajing Xu; Panpan Zhu; Jimin Shi; Weihua Zhai; Yanmin Zhao; Yang Xu; Xiaoyu Lai; Jian Yu; Lizhen Liu; Xiaolu Song; Ting Yang; Ying Lu; Kaiqian Yang; Yimei Feng; Xiaofei Ni; Jianping Lan; Xi Qiu; Yicheng Zhang; Songfu Jiang; He Huang; Erlie Jiang; Xi Zhang; Yi Luo

doi:10.1038/s41409-024-02454-5

Mismatched unrelated donors allogeneic hematopoietic stem cell transplantation with antithymocyte globulin for hematological malignancies: a multicenter retrospective study in China

Bone Marrow Transplant. 2024 Nov 8. doi: 10.1038/s41409-024-02454-5. Online ahead of print.

Authors

Lin Li^#^{1

2

3}, Yi Chen^#⁴, Ting Chen^#⁵, Yajing Xu^#^{6

7

8}, Panpan Zhu^{1

2

3}, Jimin Shi^{1

2

3}, Weihua Zhai^{9

10}, Yanmin Zhao^{1

2

3}, Yang Xu¹¹, Xiaoyu Lai^{1

2

3}, Jian Yu^{1

2

3}, Lizhen Liu^{1

2

3}, Xiaolu Song¹², Ting Yang^{13

14

15}, Ying Lu¹⁶, Kaiqian Yang⁴, Yimei Feng⁵, Xiaofei Ni^{9

10}, Jianping Lan¹², Xi Qiu¹¹, Yicheng Zhang^{17

18

19}, Songfu Jiang⁴, He Huang^{20

21

22}, Erlie Jiang^{23

24}, Xi Zhang²⁵, Yi Luo^{26

27

28}

Affiliations

¹ Bone Marrow Transplantation Center of The First Affiliated Hospital & Liangzhu Laboratory, Zhejiang University School of Medicine, Hangzhou, Zhejiang, CN, China.
² Institute of Hematology, Zhejiang University, Hangzhou, Zhejiang, CN, China.
³ Zhejiang Province Engineering Research Center for Stem Cell and Immunity Therapy, Hangzhou, Zhejiang, CN, China.
⁴ Department of Hematology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, CN, China.
⁵ Medical Center of Hematology, Xinqiao Hospital, Chongqing, CN, China.
⁶ Department of Hematology, Xiangya Hospital, Central South University, Changsha, Hunan, CN, China.
⁷ National Clinical Research Center for Geriatric Diseases (Xiangya Hospital), Changsha, Hunan, CN, China.
⁸ Hunan Hematology Oncology Clinical Medical Research Center, Changsha, Hunan, CN, China.
⁹ State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, CN, China.
¹⁰ Tianjin Institutes of Health Science, Tianjin, CN, China.
¹¹ Department of Hematology, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, CN, China.
¹² Zhejiang Provincial People's Hospital, Hematology and Hematopoietic Stem Cell Transplant Center, Hangzhou, Zhejiang, CN, China.
¹³ Department of Hematology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian, CN, China.
¹⁴ Department of Hematology, The First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian, CN, China.
¹⁵ Institute of Precision Medicine, Fujian Medical University, Fuzhou, Fujian, CN, China.
¹⁶ The Affiliated People's Hospital of Ningbo University, Ningbo, Zhejiang, CN, China.
¹⁷ Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, CN, China.
¹⁸ Key Laboratory of Organ Transplantation, Ministry of Education, NHC Key Laboratory of Organ Transplantation, Key Laboratory of Organ Transplantation, Chinese Academy of Medical Sciences, Wuhan, Hubei, CN, China.
¹⁹ Immunotherapy Research Center for Hematologic Diseases of Hubei Province, Wuhan, Hubei, CN, China.
²⁰ Bone Marrow Transplantation Center of The First Affiliated Hospital & Liangzhu Laboratory, Zhejiang University School of Medicine, Hangzhou, Zhejiang, CN, China. huanghe@zju.edu.cn.
²¹ Institute of Hematology, Zhejiang University, Hangzhou, Zhejiang, CN, China. huanghe@zju.edu.cn.
²² Zhejiang Province Engineering Research Center for Stem Cell and Immunity Therapy, Hangzhou, Zhejiang, CN, China. huanghe@zju.edu.cn.
²³ State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, CN, China. Jiangerlie@ihcams.ac.cn.
²⁴ Tianjin Institutes of Health Science, Tianjin, CN, China. Jiangerlie@ihcams.ac.cn.
²⁵ Medical Center of Hematology, Xinqiao Hospital, Chongqing, CN, China. zhangxxi@sina.com.
²⁶ Bone Marrow Transplantation Center of The First Affiliated Hospital & Liangzhu Laboratory, Zhejiang University School of Medicine, Hangzhou, Zhejiang, CN, China. luoyijr@zju.edu.cn.
²⁷ Institute of Hematology, Zhejiang University, Hangzhou, Zhejiang, CN, China. luoyijr@zju.edu.cn.
²⁸ Zhejiang Province Engineering Research Center for Stem Cell and Immunity Therapy, Hangzhou, Zhejiang, CN, China. luoyijr@zju.edu.cn.

^# Contributed equally.

PMID: 39516707
DOI: 10.1038/s41409-024-02454-5

Abstract

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) utilizing mismatched unrelated donors (MMUD) present a vital option for patients with hematologic malignancies without human leukocyte antigen (HLA)-matched donors. This multicenter retrospective study encompassed 211 adults with hematological malignancies receiving allo-HSCT with antithymocyte globulin (ATG) from ≥1 HLA locus MMUD. The findings revealed cumulative incidences of II-IV acute graft-versus-host disease (GVHD) at 180 days at 26.5%, and III-IV acute GVHD at 12.3%, with 3-year cumulative incidences for total and moderate-severe chronic GVHD at 37.0% and 21.0%. The 3-year non-relapse mortality (NRM) and relapse rates were 19.7% and 25.8%. The study reported a 3-year overall survival (OS) rate of 63.1%, a disease-free survival (DFS) rate of 54.5%, and a GVHD-free, relapse-free survival (GRFS) rate of 40.8%. Administration of a lower-dose ATG-Genzyme (ATG-G, ≤ 6 mg/kg) correlated with improved engraftment without significantly affecting survival, relapse, or viral reactivation rates. The quantity of HLA mismatches did not impact engraftment, GVHD, viral reactivation, OS, DFS, GRFS, relapse, or NRM. In conclusion, MMUD allo-HSCT with ATG demonstrates favorable outcomes for patients with hematological malignancies, with no evident correlation between the degree of mismatch and post-transplantation results. Utilizing a lower dose of ATG-G ( ≤ 6 mg/kg) proved efficacious, delivering comparable clinical advantage.