First-Line Choice for Severe Aplastic Anemia in Children: Transplantation from a Haplo-Identical Donor Versus Immunosuppressive Therapy

Background: Severe aplastic anemia (SAA) is a fatal disorder in children if treated inappropriately. According to the current algorithm, transplantation from a matched related donor (MRD) is recommended as the first-line option in children with SAA, if a MRD is unavailable, IST with a combination of anti-thymocyte globulin (ATG) and cyclosporine (CsA) represents the first-line choice. However, numerous limitations of immunosuppressive therapy (IST) exists. IST children may have incomplete recovery, and appear to be associated with an increased risk of clonal evolution and subsequent relapse. Additionally, the unavailability of horse-ATG in China also make the response of IST at a discount greatly. At the same time, great progresses in recent years in haploidentical transplantation might also promote changes in the algorithm of SAA treatment.

Methods: We retrospectively compared the outcomes of children with SAA who received IST or who underwent hematopoietic stem cell transplantation (HSCT) from a haplo-identical donor (HID) as first-line choice between 2007 and 2016. The conditioning regimen for SCT from a haploidentical donor consisted of intravenous busulfan, cyclophosphamide and rabbit ATG. All of children were administered with granulocyte colonystimulating factor (G-CSF)-primed bone marrow (BM) combined with G-CSF-primed peripheral blood (PB) hematopoietic stem cells.

Results: A total of 52 SAA children under the age of 17 years were initially treated with IST (n=24) or haplo-identical HSCT (n=28) as first-line choice. The last follow-up for all surviving patients was June 1, 2017. In IST group, by 6 months, 15 of the 21 subjects (71.4%) improved with first-line IST and achieved a partial response (n=10) or complete response (n=5). In SCT group, 27 patients (96.4%) achieved primary engraftment at a median of 12 (range, 10-21) days except one suffered from primary graft failure. The cumulative incidences (CI) of grade II-IV and of grade III-IV acute graft versus host disease (GVHD) were 48.1±1.0% and 11.1±0.4%, respectively. The 3-year CI of extensive chronic GVHD was 3.7±0.1%. The estimated 10-year overall survival were 73.4±12.6% and 89.3±5.8% in patients treated with IST or HID-HSCT (P=0.806). However, the failure-free survival was significantly inferior in patients receiving IST than in those undergoing transplantation from a HID [52.6±10.5% versus 89.3±5.8, P=0.008]. In univariate analysis, the choice of first-line immunosuppressive therapy was the only adverse predictor for failure-free survival. At the last follow-up, completely normal blood count was observed in 11 of 20 (55.0%) and 24 of 25 (96.0%) alive cases in IST and HID-HSCT cohort (P=0.003).

Conclusions: Based on the superior FFS, high rate of engraftment and acceptable incidence of GVHD, the choice of HID HSCT for SAA children without a matched related donor as a first choice option seems reasonable. These suggest that SCT from a haplo-identical donor could be considered as first-line choice in children who lack a matched related donor, especially in experienced transplantation centers.