Unmanipulated Haploidentical Transplant for Acquired Severe Aplastic Anemia Achieved Comparable Outcomes with Unrelated Donor Transplant in Adult and Children Patients

Background: Salvage BMT is considered for patients with refractory SAA if an HLA-matched unrelated donor (URD) is available, but many patients, especially minorities, are unable to find an URD in the registry . Donor availability has remained an important limitation to the success of BMT in SAA . Haploidentical donor(HID) are available for nearly all patients and can be performed immediately particularly crucial for patients with vSAA who need prompt therapy .so the past ten years ,HID has been widely used as a considered donor in HSCT for SAA. but in the early years the high rate of the primary graft failure and severe GVHD limited its clinical application.However in the recent years , with advances in in vivo regulation of T-cells, optimized conditioning regimens, and improved supportive care.The results of HID-HSCT not only have significantly increased.but also in the treatment status of SAA is increasing prominence,Even in some multicenter study,HID-HSCT be used as first line treatment for newly diagnosied SAA and achieved similar outcome to MSD-HSCT. But there are not comparable studies on HID and MUD HSCT in SAA.In order to further evalued the therapeutic effect and safety of HID SCT for the SAA, We retrospectively analysed the outcomes of 89 patients with acquired SAA who had received HID and MUD HSCT between 2012and 2016 in our single center.

Materials and methods: Between September 2012 and September 2016, total 89 patients with SAA who received unmanipulated alternative HSCT in our center were analyzed retrospectively.male to female was 52:37 . The median disease course from diagnosis to HSCT was 17(range,2 ∼ 192)months. The median age 11(range,2-42)years .64/89(71.9%)cases had heavy transfusion. 30/89(33.7%)patients received one course of ATG before transplant. Conditioning regimen consisted of busulfan (3.2 mg/kg per day) for 2 days; fludarabine (30 mg/m2 per day) for 4 days; cyclophosphamide (500 mg/m2 per day) for 4 days; and either ATG (Thymoglobuline, SANOFI, total dose 7.5 mg/kg in 42 cases; ATG-F, total dose 20 mg/kg in 47 cases) .For GVHD prophylaxis, Tacrolimus, MMF and MTX were used in all patients .

Results: Fourty-seven patients received haploidentical donors HID, and Fourty -two patients received URD for HSCT.The median times for myeloid engraftment in the HID and URD cohorts were 14 (range, 10-21) and 13 (range, 10-18)days respectively . all patients achieved primary engraftment .HID recipients had an increased cumulative incidence of grades II-IV acute GVHD (43.9± 3.48% vs 12.5± 5.52%,P=0.001), and chronic GVHD at 1 year (48.8± 3.11% vs 31.2± 2.81%.P=0.038) but similar extensive cGVHD (14.6± 2.60% vs 8.3±2.37%.P=0.244). The surviving patients with a median follow-up 26 (6-45) months, three-years overall survival (OS) was 87.8±1.46%. There were no significant differences between HID and MUD cohorts in three-year estimated OS [82.9±2.39% vs 91.7±1.70%,P=0.210], and also similar in the three-year estimated failure-free survival (FFS) [80.5±2.49% vs 91.7±1.70%,P=0.127] and GVHD free survival (GFS) [82.9±2.45% vs 81.3±2.26%,P=0.976] respectively. In multivariate analysis, survival outcome for the entire population was significantly adversely associated with VSAA (SAA vs VSAA,P=0.003) and with Ⅱ ∼ ⅣaGVHD (Yes vs No,P=0.001).but have no difference in age(< 18 years vs ≥18 years,P=0.045);disease course before HSCT(< 17 months vs ≥17 months,P=0.031);Previous Therapy before HSCT(received ATG or not, P=0..21); heavily pre-transfused before(Yes vs No,P=0.31);Type of ATG(ATG-F vs Thymoglobuline,P=0.34 );donor-patient sex match(p=0.54);donor-patient ABO blood type (P=0.23).

Conclusion: This study showed favorable outcome of Haplo-HSCT for SAA, which was comparable with UD-HSCT.Haploidentical donor can be an important alternative donor.