Comparison of Outcomes between Haploidentical and Matched Related Donors for Chronic Myelomonocytic Leukemia: A Multicenter Real-World Study

Wu, Lixin

Oral and Poster Abstracts
732. Allogeneic Transplantation: Disease Response and Comparative Treatment Studies: Poster I

Research, Clinical Research, CMML, Chronic Myeloid Malignancies, Diseases, Real-world evidence, Myeloid Malignancies

Yuqian Sun¹^*, Lixin Wu²^*, Yicheng Zhang³^*, Ya-Jing Xu⁴^*, Xiaobing Huang, MD, PhD⁵^*, Baodong Ye⁶^*, Hailong Yuan⁷^*, Jianying Zhou⁸^*, Sujun Gao⁹^*, Fang Zhou¹⁰^*, Yue Liu¹¹^*, Xianmin Song¹², Yu Cai¹³^*, Xiaoliang Liu¹⁴^*, Yi Luo¹⁵, Luxin Yang, MD¹⁶^*, Jianmin Yang¹⁷^*, Libing Wang¹⁸^*, Yuhua Li¹⁹^*, Rui Huang, MD²⁰^*, Shunqing Wang²¹^*, Ming Zhou²²^*, Yujun Dong²³^*, Qian Wang²⁴^*, Yimei Feng²⁵^*, Xin Du, M.D., Ph.D.²⁶^*, Wei Ling, M.D.²⁶^*, Han Zhu²⁷^*, Zunmin Zhu²⁸^*, Xiangli Chen²⁹^*, Shiyun Wang³⁰^*, Fankai Meng³^*, Kehong Bi³¹^*, Ning Huang³²^*, Ming Jiang³³^*, Ting Niu, MD, PhD³⁴, Jie Ji, MD, PhD³⁵^*, Dingming Wan³⁶^*, Bian Zhilei, MD³⁶^*, Yi Chen³⁷^*, Li Liu³⁸^*, Xueqian Yan³⁹^*, Xi Yang⁴⁰^*, Hai Yi, MD⁴¹^*, Xudong Wei, MD, PhD⁴²^*, Xin Li⁴³^*, Qian Cheng⁴⁴^*, Chenglu Yuan, MD⁴⁵^*, Wen Wang⁴⁶^*, Yuhong Zhou⁴⁷^*, Yu-Hong Chen, MD⁸^*, Fengrong WANG, MD⁴⁸^*, YuanYuan Zhang⁸^*, Zhi-Dong Wang, MD⁸^*, Xiao-Dong Mo, MD⁸^*, Wei Han, MD⁸^*, Jing-Zhi Wang, MD⁸^*, Yu Wang, MD, PhD⁸^*, Huan Chen, MD⁸^*, Xiangyu Zhao, MD, PhD⁸, Ying-jun Chang, PhD⁴⁹^*, Kaiyan Liu, MD, PhD⁴⁹^*, Jia Feng⁵⁰^*, LanPing Xu, MD⁵¹^*, Hongyu Zhang², Xi Zhang, PhD⁵², Xiaojun Huang⁸ and Xiaohui Zhang, MD⁸

¹National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China
²Department of Hematology, Peking University Shenzhen Hospital, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, China
³Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
⁴Xiangya Hospital of Central South University, Changsha, CHN
⁵Sichuan Academy of Medical Sciences, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, China
⁶The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, China
⁷The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
⁸Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China
⁹The First Hospital of Jilin University, Changchun, China
¹⁰Department of Hematology, Linyi Central HospitalThe 960th Hospital of The People's Liberation Army (PLA) Joint Logistics Support Force, Jinan, China
¹¹The 960th Hospital of The People's Liberation Army (PLA) Joint Logistics Support Force, Jinan, China
¹²Department of Hematology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
¹³Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
¹⁴Department of Hematology, Cancer Center, the First Hospital of Jilin University, Changchun, China
¹⁵Bone Marrow Transplantation Center of The First Affiliated Hospital & Liangzhu Laboratory, Bone Marrow Transplantation, the First Affiliated Hospital of Zhejiang Universit, Hangzhou, China
¹⁶Zhejiang Province Engineering Research Center for Stem Cell and Immunity Therapy, Hangzhou, China
¹⁷Department of Hematology, Changhai Hospital, Naval Medical University, Shanghai, AL, China
¹⁸Changhai Hospital, Shanghai, China
¹⁹Department of Hematology, Zhujiang Hospital of Southern Medical University, Guangzhou, China
²⁰Zhujiang Hospital, Southern Medical University, Guangzhou, China
²¹Department of Hematology, Guangzhou First People's Hospital, Guangzhou, China
²²Guangzhou first people’s hospital, Guangzhou, Guangzhou, CHN
²³Peking University First Hospital, Beijing, China
²⁴Peking University First Hospital, Beijing, CHN
²⁵Army medical University affiliated Xinqiao Hospital, Chongqing, China
²⁶Department of Hematology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China
²⁷Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China
²⁸Department of Hematology, Henan Provincial People's Hospital, Zhengzhou, China
²⁹Henan Provincial People's Hospital, Zhengzhou, CHN
³⁰Department of Hematology, Xiangya Hospital, Central South University, Changsha, Changsha, CHN
³¹Department of Hematology, The First Affiliated Hospital of Shandong First Medical University, Jinan, China
³²Shandong Qianfoshan Hospital, Jinan, CHN
³³Department of Hematology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
³⁴Department of Hematology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
³⁵Department of Hematology and Institute of Hematology, Department of Hematology, West China Hospital of Sichuan University, Chengdu, China
³⁶Department of Hematology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
³⁷Department of Hematology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
³⁸Department of Hematology, the Second Affiliated Hospital (Tangdu Hospital) of Air Force Medical University, Xi'an, China
³⁹Tangdu Hospital of Air Force Military Medical University, Xi'An, CHN
⁴⁰Department of Hematology, Sichuan Academy of Medical Sciences and Sichuan Provin, Chengdu, CHN
⁴¹Department of Hematology, The General Hospital of Western Theater Command, Chengdu, China
⁴²Department of Hematology, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, China
⁴³Department of Hematology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China, Changsha, Hunan, China
⁴⁴Department of Hematology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China, Changsha, China
⁴⁵Qilu Hospital of Shandong University(Qingdao), Qingdao, China
⁴⁶Department of Hematology, Qilu Hospital, Shandong University, Jinan, China
⁴⁷Department of Hematology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang, China
⁴⁸People's Hospital Institute of Hematology, Beijing, CHN
⁴⁹Peking University People’s Hospital, Peking University Institute of Hematology, Beijing, China
⁵⁰Department of Hematology, Peking University Shenzhen Hospital, Shenzhen, China
⁵¹Peking University People’s Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing, China
⁵²Medical Center of Hematology, Xinqiao Hospital of Army Medical University, State Key Laboratory of Trauma and Chemical Poisoning, Chongqing Key Laboratory of Hematology and Microenvironment, Chongqing, China

Introduction:Chronic myelomonocytic leukemia (CMML) is a heterogeneous myeloid neoplasm characterized by overlapping features of myeloproliferative neoplasm and myelodysplastic syndromes, with an incidence of approximately 1~4/100,000 per year. Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative strategy for CMML patients. Many studies have reported the benefits of allo-HSCT in these patients, especially following the risk-adapted CMML-specific prognostic scoring system (CPSS). However, few reports have investigated the outcomes of patients receiving haploidentical HSCT.

Methods: To compare the outcomes of CMML patients receiving HSCT with haploidentical donor (HID) or matched-related donor (MRD) and explore specific subgroups that may benefit from HID, we designed a multicenter real-world study from 28 centers in China. A total of 117 eligible CMML patients with HID (Beijing protocol) and 75 with MRD were enrolled. The primary endpoint was event-free survival (EFS). The secondary endpoints included overall survival (OS), cumulative incidence of relapse (CIR) and nonrelapse mortality (NRM). Risk factors were selected by univariate analysis and those with P <0.10 were subsequently included in the multivariate analysis.

Results:Patient characteristics were comparable between the two groups with P >0.05 for all variables in our study (age, sex, cytogenetics, diagnostic and pre-HSCT blood cell count and bone marrow blast, FAB and WHO classification, and so on). Neutrophil engraftment was established in all patients within 28 days. However, the engraftment time of the HID group was earlier (median, MRD vs. HID, 15 d vs. 13 d, P =0.003). Sixty-day platelet (PLT) engraftment was established in 92.3% of patients. The incidence of PLT engraftment in MRD group was slightly greater than that in HID (95.7% vs. 90.1%, P =0.173) with similar times (median, 14 d vs. 15 d, P =0.496). The cumulative incidences of grades III-IV aGVHD at 100 days were 6.8% and 9.4% in the MRD and HID groups, respectively (P =0.520). The incidence of cGVHD was also comparable (MRD vs. HID, 48.7% vs. 41.0%, P =0.308). We found that there was no significant difference between the HID and MRD groups in EFS (MRD vs. HID, 45.6% vs. 58.1%, P =0.263), OS (61.8% vs. 70.2%, P =0.503), CIR (32.8% vs. 19.1%, P =0.114) and NRM (21.6% vs. 22.8%, P =0.794). Interestingly, the EFS of patients enrolled in the post-2020 era (2020~2022) was improved in the HID group (53.0% vs. 75.7%, P =0.028). Graft source shift to peripheral blood (PB) predominancy because of COVID-19 was partially involved in the dismal outcome in the MRD group since 2020 (PB only vs. mixed grafts, EFS, 43.0% vs. 55.3%, P =0.082; OS, 50.6% vs. 86.6%, P =0.012) but not in HID (PB only vs. mixed grafts, EFS, 53.0% vs. 59.6%, P =0.590; OS, 66.1% vs. 73.1%, P =0.663). For patients with higher pre-HSCT leukemia burden, HID had a stronger antileukemic effect and thus reducing the relapse rate and improving EFS in patients with more circulating immature myeloid cells (≥1%; 23.1% vs. 67.5%, P =0.028) and splenomegaly (42.8% vs. 62.6%, P =0.034). Moreover, CMML-specific prognostic scoring system (CPSS) lower-risk patients benefited more from HID with superior EFS (15.5% vs. 77.8%, P =0.013). Multivariate analysis indicated that advanced age (P =0.002), anemia at diagnosis (P =0.018), donor relationship (parent-to-child, P =0.006), lower pre-HSCT PLT (P =0.035) and no cGVHD (P =0.006) were independently associated with worse EFS in the HID group.

Conclusion:Our data suggested that outcomes of HID modality is comparable to MRD in CMML, indicating that HID was an effective alternative for patients without MRD. And under certain conditions, such as peripheral blood graft or CPSS lower risk conditions, HID is preferred. A higher pre-HSCT PLT and younger donor age may enhance the benefit. In conclusion, our study provided a new insight into CMML patients who underwent HSCT.

Disclosures: No relevant conflicts of interest to declare.

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2187 Comparison of Outcomes between Haploidentical and Matched Related Donors for Chronic Myelomonocytic Leukemia: A Multicenter Real-World Study