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

Abstract

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 1st 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. Disclosures No relevant conflicts of interest to declare.

Relapse of Aplastic Anemia with Majority Donor Chimerism (Donor-Type Aplasia) Occurring Late after Bone Marrow Transplantation

“…South Korean data have shown a considerably higher incidence of DTA at 26.2% (11/42 patients) [19]. Similar to the Japanese studies, statistically significant associations were seen with a low infused cell dose (P = .002) and prior use of IST (P = .003).…”

“…DTA has been reported as late as 10 years after MSD transplant [16]. It is rare, having only been reported in single or small series case reports and conference abstracts, predominantly from Asia [15,[17][18][19]. We report a series of 11 patients who developed DTA after transplant for SAA from Europe, the Middle East, and the United States and focus on management and outcome.…”

Recurrent aplastic anemia with donor-type aplasia

“…[ 4 ] Its incidence varies from 5% to 26% in various studies. [ 5 6 ] A number of mechanisms have been theorized for the same. It is speculated that the destruction of the donor cells is more protracted than what was thought initially and that the “malignant” recipient clone eventually takes over the marrow again.…”

“…[ 9 ] Other factors like low infused cell number, no IST prior to HSCT, preceding transfusion >40 times and inclusion of fludarabine therapy along with CsA were associated with the development of donor-type aplasia. [ 5 6 ]…”