Haploidentical related-donor hematopoietic cell transplantation in children using megadoses of CliniMACs-selected CD34 + cells and a fixed CD3 + dose

We conducted a prospective phase II trial utilizing the CliniMACs system to perform CD34 + -cell selection of PBSCs from haploidentical donors to evaluate engraftment and hematoimmunological reconstitution. In total, 21 children with hematological malignancies or nonmalignant conditions underwent conditioning with 1200 cGy TBI, thiotepa, fludarabine and Thymoglobulin. Patients received megadoses of CD34 + cells (median: 22 × 10 6 /kg) with a fixed dose of 3 × 10 4 /kg CD3 + cells/kg, and engraftment occurred in 90% with prompt recovery of neutrophils and platelets. Grade II acute GVHD (aGVHD) was seen in 32% (95% confidence interval (CI), 15–54%) of evaluable patients, there was no grade III–IV aGVHD, and chronic extensive GVHD was seen in 35% (95% CI, 17–59%) of patients. The estimated 2-year EFS was 62% (95% CI, 48–83%) with a median survivor follow-up of 49 months (range: 18–119 months). Patients with nonmalignant diseases had an estimated 2-year EFS of 100% (95% CI, 56–100%) and patients with malignancies in remission had an estimated 2-year EFS of 56% (95% CI, 22–89%). Megadose CD34 + cells with a fixed CD3 + cell dose from haploidentical related donors resulted in good outcomes for pediatric patients with nonmalignant diseases and those with malignant diseases transplanted in remission.