Treatment and Outcome of the Patients with Donor-Type Aplasia after Bone Marrow Transplantation in Children with Aplastic Anemia

Hematopoietic stem cell transplantation (HSCT) from an HLA-matched donor is the treatment of choice for children with aplastic anemia (AA). However, graft failure (GF), either primary or secondary, remains an important and life-threatening complication. Recently, donor-type aplasia, defined as bone marrow aplasia with full donor chimerism among secondary GF, has been identified after HSCT. Clinical characteristics of donor-type aplasia after HSCT and its treatment and outcome in children with AA were retrospectively reviewed. Forty-two children with AA underwent allogeneic HSCT with 10-year overall survival rate of 85.7%. While primary GF developed in 1 (2.4%), secondary GF was seen in 12 at a median of 8 months (range: 2.0-28.5 months). Among them, 11 developed a donor-type aplasia with the cumulative incidence of 26.2%. Low infused cell number (P=0.002), immunosuppressive therapy (IST) prior to HSCT (P=0.003) and preceding transfusion >40 times (P=0.008) were associated with the development of donor-type aplasia. The survival of patients with donor-type aplasia was 81.8%. Six patients were treated with stem cell rescue as follows: peripheral blood stem cell (PBSC) boost, 3; PBSC boost followed by secondary HSCT, 2; and secondary HSCT, 1. All but 1 who had a longest interval from 1^st HSCT to stem cell rescue (54.4 months) showed restoration of graft function. The remaining 5 patients were managed with conservative measures including transfusions. No one showed spontaneous improvement with the median follow-up of 30.1 months (range, 4.2 to 43.0 months). Two patients died of graft failure and infection. Altogether, 4 patients still remain transfusion-dependent. Donor-type aplasia after HSCT for AA is not uncommon. Stem cell rescue, either with PBSC boost or secondary HSCT after conditioning should be attempted to obtain sustained graft function. For those who do not have availability for stem cell rescue, a novel treatment, such as thrombopoietin receptor agonist, should be considered for the future.