Allogeneic Hematopoietic Stem Cell Transplantation for Acute Leukemia: Comparison of Outcomes Among HLA-Matched Sibling Donors, HLA-Matched Unrelated Donors and HLA-Mismatched Family Donors
Authors: Yu Sijian , Sun Jing , Fan Zhiping , Zhang Yu , Jiang Qianli , Huang Fen , Dai Min , Zhou Hongsheng , Xu Dan , Wei Yongqiang , Xuan Li , Liu Qifa 
Published: October 2019

Abstract
Abstract Purpose: To compare the outcomes of acute leukemia undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) from HLA-matched sibling donors (MSDs), HLA-matched unrelated donors (MUDs), and HLA-mismatched family donors (MFDs).
Method: A total of 358 consecutive patients with acute leukemia undergoing allo-HSCT at our single institute between April 2008 to December 2013 were enrolled in this retrospective investigation. The outcomes including graft-versus-host disease (GVHD), transplantation related mortality (TRM), leukemia relapse and survival were analyzed.
Results: Of the 358 patients, 158 patients received MSDs, 105 MUDs and 95 MFDs transplantation. Based on clinical and cytogenetic features, there were 50.6%, 67.6% and 81.5% of high-risk patients in the MSDs, MUDs and MFDs groups, respectively (P=0.002). All patients achieved full engraftment, except for 1 died from regimen related toxicity (RRT) and 3 from early infections. Hematopoietic engraftment was faster in the MSDs group than that in the MUDs and MFDs groups (p<0.001).The cumulative incidence of grade II to IV acute GVHD (aGVHD) were 23.4%±3.4%, 34.3%±4.6% and 41.3%±5.1% in the MSDs, MUDs and MFDs groups, respectively (P=0.003), while the cumulative incidence of grade III to IV severe grade aGVHD were not different among the three groups (8.2%±2.3%, 10.6%±3.2%, 12.1%±3.8%, respectively; P=0.858). The cumulative incidence of chronic GVHD (cGVHD)were 33.0%±3.9%, 37.1%±4.7% and 37.9%±5.0% in the MSDs, MUDs and MFDs groups, respectively (P=0.735). Median follow-up was 33.5 months, the 3-year cumulative incidence of leukemia relapse was 28.9%±4.3%, 31.7%±5.4% and 26.9±6.1%, in the three groups, respectively (P=0.698). The 5-year cumulative incidence of TRM in MSDs and MUDs groups were lower than that in MFDs group (23.5%±6.3% , 24.3%±4.5% and 34.1±6.3%, respectively; P=0.014).The 5-year overall survival (OS) post-transplantation were 56.8%±5.7%, 55.7%±5.1% and 50.5%±6.2% (P=0.138), and disease-free survival (DFS) were 54.7%±5.6%, 49.2%±5.3% and 46.3%±6.2% (P=0.070), which did not differ among the three groups. In the multivariate analysis, number of chemotherapy cycles before transplantation, donor age, aGVHD and cGVHD were significant factors affecting TRM, which was not relevant to donor types. And high-risk cytogenetics was the common risk factor for relapse and survival.
Conclusions: Our results suggest that HLA-mismatched family donors are alternative choice for patients with acute leukemia undergoing HSCT when HLA-matched donors are not available.

Disclosures
Xuan: It was supported by National Natural Science Foundation of China (81270647, 81300445, 81200388); National High Technology Research and Development Program of China (863 Program) (2011AA020105): Research Funding. Liu:It was supported by National Natural Science Foundation of China (81270647, 81300445, 81200388); National High Technology Research and Development Program of China (863 Program) (2011AA020105); National Public Health Grand Research Foundation (201202017);: Research Funding; It was supported by Natural Science Foundation of Guangdong Province (S2012010009299); the project of health collaborative innovation of Guangzhou city (201400000003-4, 201400000003-1);: Research Funding; It was supported by the Technology Plan of Guangdong Province of China (2012B031800403); the project of the Zhujiang Science & Technology Star of Guangzhou city (2013027).: Research Funding.