Upfront haploidentical hematopoietic cell transplantation using αβ+ T cell-depleted peripheral blood stem cells for pediatric patients with acquired severe aplastic anemia.

Abstract

Background: Allogeneic hematopoietic cell transplantation (HCT) using a haploidentical family donor (HFD) is an accepted option for patients with severe aplastic anemia (SAA) without a matched related or unrelated donor. Although HFDs have been used as alternative donors for HCT in refractory SAA, upfront use requires further evidence.

Objective(s): In this study, we evaluated the outcomes of ex vivo αβ⁺ T cell-depleted haploidentical HCT (haplo-HCT) as a front-line therapy for pediatric patients with acquired SAA who were treatment-naïve.

Study design: A total of 37 pediatric patients underwent haplo-HCT using ex vivo αβ⁺T cell-depleted peripheral blood stem cells between December 2015 and July 2024. The conditioning regimen consisted of fractionated total body irradiation (TBI) and rabbit ATG (rATG), along with fludarabine (180 mg/m²) and cyclophosphamide (100 mg/kg). Twelve patients were administered TBI at 400 cGy combined with rATG at 7.5 mg/kg, while the remaining 25 patients were administered TBI at 600 cGy with rATG at a dose of ≤ 5 mg/kg. Ex vivo depletion of αβ⁺ T cells was the graft-versus-host disease (GVHD) prophylaxis approach in our haplo-HCT platform without immunosuppressants or with only mycophenolate mofetil (MMF) for 1month post-transplant. Donors comprised 10 mothers, 14 fathers, and 13 siblings.

Results: 36 patients achieved neutrophil engraftment at a median of 10 days (range, 9-12) after haplo-HCT. One patient experienced primary graft failure (GF). Another patient experienced late GF, and 1 patient had poor graft function. All of these patients were rescued with subsequent haplo-HCT. The cumulative incidence (CI) rates for ≥ grade 2 and ≥ grade 3 acute GVHD (aGVHD) were 37.1% and 11.5%, respectively. No patient developed grade 4 aGVHD. The CI for moderate-to-severe chronic GVHD (cGVHD) was 5.9%. All grade 3 aGVHD and cGVHD cases were observed among patients who received 600 cGy TBI. In contrast, CMV disease and EBV reactivation were significantly prevalent among patients who received 400 cGy compared with 600 cGy TBI (P=.016 and P≤.001). Overall, 2 patients died from transplant-related mortality, and 35 patients survived with complete donor chimerism and were free of transfusion. At a median follow-up of 60 months (range, 6-111), overall survival and failure-free survival rates were 94% ± 3.9% and 89% ± 5.3%, respectively. Survival rates were not significantly different according to the doses of TBI or rATG as part of the conditioning regimen.

Conclusions: Our upfront haplo-HCT platform using αβ⁺ T cell-depleted peripheral blood stem cellsmay be a realistic alternative for pediatric patients with acquired SAA who have no suitable related or unrelated donors.