单倍型造血干细胞联合第三方脐血干细胞移植治疗重型再生障碍性贫血127例临床观察

OBJECTIVE: To evaluate the outcome of combination of haploidentical donor (HID) hematopoietic stem cell transplantation (HSCT) with an unrelated cord blood unit for severe aplastic anemia (SAA). METHODS: The clinical data of 127 SAA patients [including 74 male and 53 female patients, 65 very severe aplastic anemia (vSAA), the median age as 23.5(3–54) years] received HID-HSCT from September 2011 to April 2017 were analyzed retrospectively. The median interval from SAA diagnosis to transplantation was 2 (0.5–180) months. The conditioning was modified Bu/Cy+ATG/ALG-based (Busulfan + cyclophosphamide + antithymocyte immunoglobulin/antilymphocyte immunoglobulin) regimen. Cord blood units were selected based on the results of HLA typing and cell doses evaluated before freezing. Units with at least 4/6 matched HLA loci became the candidates. Prophylaxis for graft-versus host disease (GVHD) was by cyclosporine (CsA), mycophenolate mofetil (MMF) plus short-term methotrexate (MTX). RESULTS: The median values of absolute nucleated cell counts were 10.87 (3.61–24.00)×10(8)/kg in the haploidentical grafts and 2.22 (1.10–7.30)×10(7)/kg in the cord blood units, respectively. The median doses of CD34(+) cells infused were 3.49(1.02–8.89)×10(6)/kg in the haploidentical grafts and 0.56 (0.16–2.27)×10(5)/kg in the cord blood units, respectively. Of the 127 patients, 5 patients occurred early death, one patient occurred primary graft failure. All 121 surviving patients attained complete haploidentical engraftment. The median durations of myeloid engraftment were 11 (9–28) days and 15 (9–330) days for platelets, with a cumulative platelet engraftment incidence of 96.1%. The incidence of infection was 58.27% (74/127). During a median follow-up of 20.5 (4–60) months, the incidence of grade Ⅱ–Ⅳ acute GVHD was 24.79% (30/121), moderate-severe chronic GVHD was 14.15% (15/106), 4-year estimated overall survival was (78.5±4.3) %, 4-year estimated failure-free survival was (77.4±4.3) %, respectively. CONCLUSION: Combination of HID-HSCT and an unrelated umbilical cord blood unit was a feasible choice with favorable outcome for SAA patients without matched donors.