Outcomes of Unrelated Donor Stem Cell Transplantation with Partial T Cell Depletion for Pediatric Patients with Hemoglobinopathies
Researchers at the Children’s Hospital of Philadelphia and collaborators evaluated outcomes of unrelated donor peripheral blood stem cell transplantation (URD-PSCT) with partial T cell depletion (pTCD) in pediatric patients with sickle cell disease (SCD) and transfusion-dependent beta thalassemia (TDT). This study addressed the longstanding challenge of most patients lacking matched related donors, with alternative donor strategies often carrying high risks of graft failure, graft-versus-host disease (GVHD), or delayed immune recovery. By using CD3+/CD19+ or TCRαβ+/CD19+ depletion platforms, the investigators aimed to balance engraftment success with protection against severe GVHD.
Between 2017 and 2023, sixteen children underwent URD-PSCT using either fully matched (10/10) or single-allele mismatched (9/10) donors with a median follow-up period of 36 months. All patients achieved rapid trilinear engraftment, with median neutrophil recovery at 14 days and platelet engraftment at 15.5 days - substantially faster than gene therapy recipients at the same center, who required a median of 51 days. The one- and three-year overall survival rates were 93.8%, with a three-year graft failure-free survival of 81.3%. Durable donor chimerism was achieved in all patients with TDT (all 9/10 donors) and in SCD patients with 10/10 matched donors. However, graft failure occurred in three of five SCD patients with 9/10 matched donors, despite prophylaxis such as abatacept, which was administered in one case.
Of note, no patients developed severe (grade III–IV) acute GVHD or moderate-to-severe chronic GVHD. Further, immune reconstitution was robust, with T, B, and NK cell recovery within the first year, with infection rates comparable to other transplant settings. The authors concluded that URD-PSCT with pTCD offers excellent survival, engraftment, and GVHD outcomes in pediatric patients with TDT and SCD receiving fully matched unrelated grafts. However, the unacceptably high rate of graft failure among SCD patients with 9/10 matched donors highlights the need for new strategies in this subgroup, with pTCD remaining a strong option for patients otherwise ineligible for gene therapy.
Reference:
Gibson NM, Elgarten CW, Oved JH, et al. Outcomes of Unrelated Donor Stem Cell Transplantation with Partial T Cell Depletion for Pediatric Patients with Hemoglobinopathies. Transplant Cell Ther. Published online July 1, 2025.