Outcomes of Unrelated Donor Stem Cell Transplantation with Partial T Cell Depletion for Pediatric Patients with Hemoglobinopathies

Nora M Gibson; Caitlin W Elgarten; Joseph H Oved; Lisa Wray; Jason Freedman; Eugene Khandros; Elizabeth Worster; Peter Nicholas; Stephan Kadauke; Yongping Wang; Stephan Grupp; Janet L Kwiatkowski; Timothy S Olson

doi:10.1016/j.jtct.2025.06.029

Outcomes of Unrelated Donor Stem Cell Transplantation with Partial T Cell Depletion for Pediatric Patients with Hemoglobinopathies

Transplant Cell Ther. 2025 Jul 1:S2666-6367(25)01272-2. doi: 10.1016/j.jtct.2025.06.029. Online ahead of print.

Affiliations

¹ Cell Therapy and Transplant Section, Division of Oncology, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA.
² Division of Pediatric Transplantation & Cellular Therapies, Memorial Sloan Kettering Cancer Center, New York NY, USA.
³ Division of Hematology, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA.
⁴ Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA.
⁵ Cell Therapy and Transplant Section, Division of Oncology, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA. Electronic address: olsont@chop.edu.

PMID: 40609743
DOI: 10.1016/j.jtct.2025.06.029

Abstract

Background: 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.

Methods: 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 three 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 four patients, and TCRαβ+ T cell/CD19+ depletion in 12 patients.

Results: Median follow-up is 36 months (range 10-57). 1- and 3-year overall survival is 93.8%, and 3-year graft failure-free survival is 81.3%. One patient with pre-existing severe cerebrovasculopathy died from cerebral hemorrhage. All patients demonstrated rapid trilinear engraftment, and notably rapid platelet engraftment. No patients developed Grade III-IV acute GvHD or moderate to severe chronic GvHD. All six patients with SCD receiving 10/10 matched donor grafts and all patients with BTM (all five had 9/10 matched donors) exhibited durable engraftment with median total donor chimerism 95% (range 88-100%) at last follow-up. Three of five 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.

Conclusions: 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.

Keywords: Partial T cell depletion; allogeneic transplant; alternative donor; hemoglobinopathies.