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2109 Changing Donor Was Critical for the Successful Salvage Second Transplantation for Graft Failure after the First Allogeneic Stem Cell Transplantation: A Chinese Multicenter Retrospective Study

Program: Oral and Poster Abstracts
Session: 721. Allogeneic Transplantation: Conditioning Regimens, Engraftment, and Acute Toxicities: Poster I
Hematology Disease Topics & Pathways:
Research, Clinical Research, Real-world evidence
Saturday, December 7, 2024, 5:30 PM-7:30 PM

Rui MA1*, Xiaoyu Zhu2, Jianping Zhang3*, Jia Chen4*, Li Xuan5*, Hailong Yuan6*, Yang Cao7*, Weijie Cao, MD8*, Xiaosheng Fang9*, Kourong Miao10*, Xiaoxia Hu11*, Hai Yi, MD12*, Yanmin Zhao, MD13*, Yuanbin Wu14*, Ting Yang15*, Hongtao Wang16*, Yue Yin17*, Zhongming Zhang18*, Xiaojun Huang19 and Yuqian Sun19*

1Peking University People's Hospital, Peking University Institute of Hematology, BEIJING, VA, China
2Department of Hematology, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China
3Beijing Lu Daopei Hospital, Beijing, China
4National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China
5Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, China
6The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
7Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
8Department of Hematology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
9Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
10People's Hospital of Jiangsu Province, Suzhou, China
11Ruijin Hospital, SHANGHAI, China
12Department of Hematology, The General Hospital of Western Theater Command, Chengdu, China
13Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
14Guangdong Hospital of Traditional Chinese Medicine, Guangzhou, China
15Department of Hematology, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
16Department of Hematology, Shengjing Hospital of China Medical University, Shenyang, China
17Peking University First Hospital, Beijing, China
18Department of Hematology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
19Peking University People's Hospital, Peking University Institute of Hematology, Beijing, China

AIMS

A second transplantation was almost the only salvage for patients encountering graft failure (GF) after the first allogeneic stem cell transplantation (allo-HSCT). However, there were no standard protocols for second transplantations regarding conditioning regimens and second donor selections. The very promising outcomes of our novel protocol for second transplantation (fludarabine/cyclophosphamide-based conditioning with changing a different donor) suggested that changing donors might be an important factor (Bone Marrow Transplant, 2024, 59: 991-996). However, the role of changing donors in second transplantations was still controversial. Therefore, the current study aims to present the status of second transplantation for GF in China, and to further explore factors associated with second transplantation outcomes.

METHODS

From Jan 2000 to Dec 2023, consecutive patients who received a second transplantation due to GF from 18 centers in China were retrospectively studied. The primary endpoint was the engraftment of neutrophil. Other endpoints included platelet engraftment, acute and chronic graft versus host disease (GVHD), transplant related mortality (TRM), relapse, and survival. Univariate and multivariate analysis were performed to explore prognostic factors for second transplant outcomes, especially the possible effect of changing donors.

RESULTS

A total of 272 patients from 18 centers were analyzed, including 193 (71.0%) primary GF and 79 (29.0%) secondary GF. Donors of the first transplantation included haploidentical donors (HIDs, n=147, 54.0%), cord blood (CB, n=81, 29.8%), matched related donors (MRDs, n=25, 9.2%), and unrelated donors (URDs, n=19, 7.0%). A different donor was used in 192 (70.6%) patients in the second transplantation, whilst the remaining patients (n=80, 39.4%) retained the initial donor. Conditioning regimens were heterogenous, among which fludarabine and cyclophosphamide-based regimen was the most commonly used (81/272, 29.8%). In the entire cohort, neutrophil engraftment was achieved in 218 (86.3%) patients by d28, and platelet engraftment was achieved in 164 (70.0%) patients by d100. The 3-year cumulative incidence of acute GVHD, chronic GVHD, relapse, and TRM were 43.5%, 27.8%, 15.6%, and 44.6%, respectively. The 1-year and 3-year probabilities of overall survival (OS) were 56.1% and 49.5%, respectively. Compared to second transplantations with the same donor, changing to a different donor was related to improved neutrophil (92.4% vs 71.4%, p<0.001) and platelet engraftment (76.9% vs 51.8%, p<0.001), reduced 1-year TRM (34.8% vs 56.3%, p<0.001), and superior OS (61.9% vs 42.7%, p<0.001). In cases grafted from MRDs, URDs, and HIDs, second transplantations using a different donor also showed better outcomes, demonstrated by neutrophil engraftment (94.7% vs 71.4%, p<0.001), platelet engraftment (83.0% vs 51.8%, p<0.001), TRM (30.4% vs 56.3%, p<0.001), and OS (66.6% vs 42.7%, p<0.001), in comparison with using the initial donors. Multivariate analysis further confirmed the association between changing donors and improved neutrophil engraftment (changing donor vs using the same donor, HR 0.634, p=0.023), platelet engraftment (HR 0.535, p=0.018), TRM (HR 0.420, p=0.001) and survival (HR 0.564, p=0.026). In subgroup analysis performed in patients with hematological malignancies, changing donors was also related to increased chances of platelet engraftment (changing donor vs using the same donor, HR 0.495, p=0.038), survival (HR 0.505, p=0.021), and decreased TRM (HR 0.459, p=0.017).

CONCLUSIONS

To our knowledge, this is the largest multicenter study of second transplantations for GF. Our study suggested that changing a different donor, rather than other factors, might be critical for engraftment and patient survival after second transplantations.

Disclosures: No relevant conflicts of interest to declare.

*signifies non-member of ASH