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
Authors: MA Rui , Zhu Xiaoyu , Zhang Jianping , Chen Jia , Xuan Li , Yuan Hailong , Cao Yang , Cao Weijie , Fang Xiaosheng , Miao Kourong , Hu Xiaoxia , Yi Hai , Zhao Yanmin , Wu Yuanbin , Yang Ting , Wang Hongtao , Yin Yue , Zhang Zhongming , Huang Xiaojun , Sun Yuqian 
Published: December 2024

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.