Outcome and Prognostic Factors for Pediatric Patients Receiving an Haploidentical Transplantation Using CD3/CD19 Depleted Grafts

Haploidentical hematopoietic stem cell transplantation using T-cell depleted grafts (haploHSCT) is an option for pediatric patients with high-risk hematological malignancies lacking an HLA-identical donor. Since December 2006 to September 2013;  55 children underwent an haploHSCT using CD3+/CD19+ depletion for graft manipulation. Eleven patients were in 1st CR, 22 in 2nd CR and 22 were in >2nd CR at time of transplantation. The conditionig regimen consisted of 30 mg/m2/d of i.v. fludarabine on days -6 to -2, 3.2-4.8 mg/kg/day of  i.v. busulfan on days -6 and -4 and 5 mg/kg/day of  i.v. thiotepa on days -3 to -2. PBPC were mobilized and collected in the standard manner. GvHD prophylaxis included CsA 3 mg/kg/day from day -1. Allografts contained a median of 5.75 x10⁶ CD34 cells/kg and 1.0 x 10⁴ CD3 cells/kg. Median times to neutrophil and platelet recovery were 13 and 10 days, respectively. The probability of aGvHD and cGvHD were 13±5% and 31±10% respectively. NRM was 14±5% by day +100 and 21±6% by 2 years after transplant. Cause of dead were relapse in 9 cases, severe viral infections in 7 and graft failure in 2. The probability of relapse was 29±8%. With a median follow-up of 24 months, the probability of DFS was 55±8%. On a multivariate analysis the factors that positive impact on DFS were age below 12 years (HR;0.26, 95%CI: 0.09-0.79 p<0.009) and cGvHD (HR;0.68, 95%CI: 0.01-0.53 p<0.01).  Our results suggest that haploidentical donors are a good option for pediatric patients with high-risk hematological malignancies who need an allogeneic transplantation. Graft manipulation resulted on low incidence of severe aGvHD. DFS was better for patients with cGvHD mainly due to lower relapse incidence. Severe viral infections is a relevant problem in the early phase after transplantation.