A Busulfan Following Cyclophosphamide and Constant Cell Dose Protocol Improved Results in Alternative Donor Hematologic Stem Cell Transplantation in Thalassemia Major: A Result from Long-Term Large-Size Multi-Center Study

Sibling donor transplantation (SDT) is a proven curative therapy for patients with thalassemia major (TM), NF-08-TM protocol improved the outcomes of unrelated donor transplantation (UDT) in single-center. This study aim was to determine whether outcomes of NF-08-TM protocol could be proved in multicenter and long-term follow-up and to compare the outcomes of full-matched (FM) and one-locus mismatch (WM) UDT. 586 patients from 4 pediatric BMT centers in China from Dec. 2008 to Jun. 2016 received NF-08-TM protocol, a newly designed Busulfan following Cyclophosphamide and constant cell dose protocol. With a median follow-up of 57 months (range, 21-116), the 9-year OS, TFS, GR, and TRM were 94.4%, 92.8%, 2.7%, and 5.6%, respectively, in total. The corresponding rates for SDTs (n=224) were 95.9%, 95.5%, 1.4% and 4.1%; for UDTs (n=275) were 92.4%, 89.9%, 4.3% and 7.6%; for parental donor transplantation (PDT, n=40) were 95.0%, 95.0%, 0% and 5.0%; and for cord blood transplantation (CBT, n=47) were 97.9%, 95.4%, 2.6% and 2.1%, respectively.The incidence of grade II-IV aGVHD, III-IV aGVHD, mild cGVHD and moderate/severe cGVHD of the entire cohort was 8.9%, 4.6%, 3.7%, and 1.4%, respectively. There was no statistically significant difference (SSD) in OS, TFS, TRM, and GR when comparing FM-SDTs with those of FM-PDTs, FM-UDTs or FM-CBTs. Among PDTs, no SSD was found in OS, TFS, TRM, GR, and GVHD in comparison of FM-PDTs and WM-PDTs. More moderate/severe cGVHD occurred in WM-UDTs than FM-UDTs. Compared FM-SDTs, WM-UDTs had worse OS, TFS, TRM, and a higher rate of grade II-IV aGVHD and cGVHD. Current study proved that Good outcomes of NF-08-TM protocol in single-center be proved in multicenter and long-term follow-up. Compared to the outcomes of FM-UDT) those of well-UDT was worse and was not recommended to thalassemia patients.