TCR α+ β+ /CD19+ cell-depleted hematopoietic stem cell transplantation for pediatric patients

Abstract

TCR α⁺ β⁺ /CD19⁺ cell depletion is an emerging technique for ex vivo graft manipulation in HSCT. We report 20 pediatric patients who underwent TCR α⁺ β⁺ /CD19⁺ cell-depleted HSCT in four Australian centers. Conditioning regimen was dependent on HSCT indication, which included immunodeficiency (n = 14), Fanconi anemia (n = 3), and acute leukemia (n = 3). Donor sources were haploidentical parent (n = 17), haploidentical sibling (n = 2), or matched unrelated donor (n = 1). Mean cell dose was 8.2 × 10⁸ /kg TNC, 12.1 × 10⁶ /kg CD34⁺ cells, and 0.4 × 10⁵ /kg TCR α⁺ β⁺ cells. All patients achieved primary neutrophil and platelet engraftment, with average time to neutrophil engraftment 11 days (range 8-22) and platelet engraftment 24 days (range 12-69). TRM at 1 year was 15%. Rate of grade II-IV aGVHD at 1 year was 20% with no grade III-IV aGVHD seen. CMV reactivation occurred in 81% of CMV-positive recipients, with one patient developing CMV disease. Average time to CD4 recovery (>400 × 10⁶ /L) was 258 days. Overall survival for the cohort at 5 years was 80%. This report highlights the initial experience of TCR α⁺ β⁺ /CD19⁺ cell-depleted HSCT in Australian centers, with high rates of engraftment, low rates of aGVHD, and acceptable TRM.

Keywords: TCR αβ depletion; haematopoietic stem cell transplant; immunodeficiency.