Comparison of Outcomes between Haploidentical and Matched Related Donors for Chronic Myelomonocytic Leukemia: A Multicenter Real-World Study
Authors: Sun Yuqian , Wu Lixin , Zhang Yicheng , Xu Ya-Jing , Huang Xiaobing , Ye Baodong , Yuan Hailong , Zhou Jianying , Gao Sujun , Zhou Fang , Liu Yue , Song Xianmin , Cai Yu , Liu Xiaoliang , Luo Yi , Yang Luxin , Yang Jianmin , Wang Libing , Li Yuhua , Huang Rui , Wang Shunqing , Zhou Ming , Dong Yujun , Wang Qian , Feng Yimei , Du Xin , Ling Wei , Zhu Han , Zhu Zunmin , Chen Xiangli , Wang Shiyun , Meng Fankai , Bi Kehong , Huang Ning , Jiang Ming , Niu Ting , Ji Jie , Wan Dingming , Zhilei Bian , Chen Yi , Liu Li , Yan Xueqian , Yang Xi , Yi Hai , Wei Xudong , Li Xin , Cheng Qian , Yuan Chenglu , Wang Wen , Zhou Yuhong , Chen Yu-Hong , WANG Fengrong , Zhang YuanYuan , Wang Zhi-Dong , Mo Xiao-Dong , Han Wei , Wang Jing-Zhi , Wang Yu , Chen Huan , Zhao Xiangyu , Chang Ying-jun , Liu Kaiyan , Feng Jia , Xu LanPing , Zhang Hongyu , Zhang Xi , Huang Xiaojun , Zhang Xiaohui 
Published: December 2024

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 &lt;0.10 were subsequently included in the multivariate analysis.

Results:Patient characteristics were comparable between the two groups with P &gt;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.