Immunological recovery following HLA-matched CD3+TCR alpha ss+/CD19+depleted hematopoietic stem cell transplantation in children

Background Allogeneic hematopoietic stem cell transplantation (HSCT) is a potentially curative option for children with both malignant and nonmalignant diseases. T-cell depletion techniques may result in reduced transplant-related mortality compared with unmanipulated grafts due to a lower incidence of GvHD. Methods Immune recovery and outcome were analyzed in a cohort of 23 patients with malignant and nonmalignant diseases who received CD3+TCR alpha beta+ T- and B-cell-depleted allografts from matched donors after reduced-intensity or myeloablative conditioning. The median number of CD34+, CD3+TCR alpha beta+, and CD19+B-cells infused was 12.7 x 10(6)/kg, 16.8 x 10(3)/kg, and 96 x 10(3)/kg bodyweight. Results With a median follow-up of 36 (range 1-73) months, overall survival and disease-free survival at 3 years were 65.2% and 60.8%. Eight patients died, six due to the underlying disease and two of extended visceral cGvHD. Immune reconstitution, disease-free, and overall survivals were similar compared with a historical cohort of 23 patients transplanted with matched unmanipulated bone marrow. A significant lower rate of higher grade (III-IV) aGvHD was observed in the manipulated HSCT group (8.7% vs. 26%; p = 0.001), whereas the incidence of cGvHD was equal. Conclusions Our data suggest that this graft manipulation strategy could be a safe and effective alternative to conventional HSCT techniques in matched donors.