| Abstract: |
Optimal methods of alternative donor allogeneic transplant for pediatric patients with sickle cell disease (SCD) and beta thalassemia major (BTM) lacking matched related donors have remained elusive. Most studies demonstrate unacceptable rates of graft rejection, graft-versus-host disease, and/or organ toxicity in children. Ex vivo partial T cell depletion (pTCD) of unrelated donor peripheral stem cell (URD-PSC) grafts has the potential to facilitate durable engraftment while preventing GVHD. We present a single-center analysis of URD pTCD-PSCT for pediatric patients with SCD and BTM. Sixteen patients underwent URD-SCT with 10/10 or 9/10 HLA-matched donors across 3 clinical trial protocols. Conditioning included hydroxyurea, thymoglobulin, fludarabine, thiotepa, and busulfan. Graft manipulation included CD3+/CD19+ depletion with 1 × 105 CD3+ cells/kg addback in 4 patients, and TCRαβ+ T cell/CD19+ depletion in 12 patients. Median follow-up is 36 months (range 10 to 57). One- and 3-year overall survival is 93.8%, and 3-year graft failure-free survival is 81.3%. One patient with preexisting severe cerebrovasculopathy died from cerebral hemorrhage. All patients demonstrated rapid trilinear engraftment, and notably rapid platelet engraftment. No patients developed Grades III and IV acute GVHD or moderate-to-severe chronic GVHD. All 6 patients with SCD receiving 10/10 matched donor grafts and all patients with BTM (all 5 had 9/10 matched donors) exhibited durable engraftment with median total donor chimerism of 95% (range 88% to 100%) at last follow-up. 3 of 5 patients with SCD receiving 9/10 HLA-matched donor grafts experienced graft failure. Two of these patients had lasting engraftment and resolution of disease phenotype with a second transplant. URD-PSCT with pTCD is associated with excellent engraftment, overall survival, and minimal GVHD in patients with SCD receiving 10/10 URD grafts and patients with BTM with ≥9/10 URD grafts. © 2025 The Authors |
