Haploidentical Hematopoietic Stem Cell Transplantation in Pediatric Patients with Acquired Severe Aplastic Anemia: Collaborative Study of Three Eastern Asian Countries

Haploidentical hematopoietic stem cell transplantation (HHCT) is indicated for patients with severe aplastic anemia (SAA) who need emergent HCT or for those with refractory SAA who lack a matched related or unrelated donor.°°We evaluated the outcomes of children and adolescents with acquired SAA who received HHCT at three transplant centers in Eastern Asia. This collaborative study reports the feasibility and efficacy of HHCT in children and adolescents with acquired SAA.

Between May 2006 and February 2014, 33 patients received HHCT at Asan Medical Center Children’s Hospital in Seoul (n=18), Shanghai Children’s Medical Center (n=8), and Nagoya University Hospital (n=7). Eighteen patients received in vitro T cell-depleted transplantation (TCD-HHCT) and 15 received a graft without in vitro manipulation (non-TCD-HHCT). Of the 33 patients, 27 had failed immnosuppressive therapy prior to HHCT. The donors were the mother in 15 patients, the father in 14, and a sibling in four. The conditioning regimen consisted of fludarabine (FLU), cyclophosphamide (CY), and rabbit ATG (r-ATG) with or without total body irradiation (TBI) in 18 patients who received TCD-HHCT. In the 15 patients who received non-TCD-HHCT, FLU/CY/ATG was used as a conditioning regimen for eight patients and FLU/melphalan/r-ATG/TBI for seven patients.

Among the 33 patients, 31 achieved neutrophil engraftment at a median of 12 days (range, 9–34 days) after HHCT. Two patients (one with TCD-HHCT and one with non-TCD-HHCT) failed to achieve primary engraftment. An additional four patients who received TCD-HHCT experienced graft rejection (GR) soon after engraftment, although no patients who received non-TCD-HHCT experienced GR. All of the five patients who experienced early graft failure (GF) after TCD-HHCT received a second HHCT and achieved sustained engraftment. The patient who experienced GF after non-TCD-HHCT died of infection after the second HHCT from the same donor at D+54 from the first HHCT. Acute graft versus host disease (aGVHD) was assessed in 27 patients, excluding the six patients with early GF. Thirteen of the 27 patients developed grade II to IV aGVHD (8 grade II, 4 grade III and 1 grade IV) leading to a cumulative incidence of 48.1%. And five patients developed extensive chronic GVHD. Of the total of 33 patients, three patients (one with TCD-HHCT and two with non-TCD-HHCT) died of TRM. One patient died of severe autoimmune hemolytic anemia after a booster infusion of CD34⁺ cells for poor graft function at +457 days, one died of infection after salvage transplantation for GF at +54 days from his first HHCT, and one died of pulmonary complications at +236 days. At a median follow-up of 28 months (range, 4-99 months), the overall survival at 2 years was 90.1% (95% CI, 80.7-100%) and all 30 surviving patients were transfusion-independent.

Our study suggests that HHCT with or without in vitro T cell depletion is a realistic therapeutic option for pediatric patients with SAA who lack a matched related or unrelated donor.