Outcomes of Combination of HLA-Haploidentical Hematopoietic SCT with an Unrelated Cord Blood Unit for 127 Patients with Acquired Severe Aplastic Anemia

Haploidentical donor (HID) hematopoietic stem cell transplantation (HSCT) is an alternative treatment method for severe aplastic anemia (SAA) patients lacking suitable identical donors and those who are refractory to immunosuppressive therapy (IST). Studies have evaluated the feasibility of upfront haploidentical HSCT in SAA patients. We previously conducted a single-arm prospective study in 50 patients who received the combination of HID-HSCT and an unrelated umbilical cord blood unit for the treatment of hematological malignancies. To the best of our knowledge, there is no combination of HID-HSCT and an unrelated umbilical cord blood unit for SAA. Now, we report the outcomes of combination of HID-HSCT with an unrelated cord blood unit for 127 patients with SAA in our center from September 2011 to April 2017. The clinical data of 127 SAA patients, including 74 male patients and 53 female patients, 65 very severe aplastic anemia (vSAA), the median age was 23.5 years (range 3.0-54.0). 39 patients of failure to IST as salvage therapy, 88 patients underwent upfront transplantation. The median interval from SAA diagnosis to SCT was 2.0 months (range 0.5-180.0). 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, and HLA matching was prioritized over cell dose. At the same level of typing, the richest UCB units were chosen. The conditioning regimen was modified BU/CY-based regimen. Prophylaxis for graft-versus host disease (GVHD): cyclosporine (CsA), mycophenolate mofetil (MMF) plus short-term methotrexate (MTX). The median values of absolute nucleated cell counts were 10.87 (3.61-24.00)×10⁸/kg in the haploidentical grafts and 2.22 (1.10-7.30)×10⁷/kg in the cord blood units. The median doses of CD34⁺ cells infused were 3.49(1.02-8.89)×10⁶/kg and 0.56 (0.16-2.27)×10⁵/kg, respectively. One patient occurred primary graft failure. All surviving patients attained complete haploidentical engraftment. The median time for myeloid engraftment was 11 (range, 9-28) days and 15 (range, 9-330) days for platelets, with a cumulative platelet engraftment incidence of 96.1%. With a median follow-up of 20.5(4.0-60.0) months, the incidence of grade II-IV acute graft-versus-host disease (aGVHD) was 24.8%, moderate-severe chronic GVHD was 14.4%, 4-year estimated overall survival (OS) was 78.5% ± 4.3%. In conclusion, combination of HID-HSCT and an unrelated umbilical cord blood unit is a feasible choice for SAA with favourable outcomes.