A comparison between three graft manipulation methods for haploidentical stem cell transplantation in pediatric patients:: Preliminary results of a pilot study

Transplantation of hematopoietic stem cells from mismatched related donors makes a potential donor available for every child in need of stem cell transplantation. Here, we compare three different graft manipulation methods in patients with leukemias and lymphomas: positive selection of stem cells with either CD34 (n = 39) or CD133-coated magnetic microbeads (n = 14) and a new strategy which depletes T- and B-cells through the use of CD3- and CD19-coated microbeads (n = 11). Median purity of stem cells was comparable after CD34(+)-selection and CD133(+)-selection, whereas stem cells were only slightly enriched after CD3(+)/CD19(+)-depletion (97.5%, 93.4% and 1.02%). Indirect depletion of T-cells by positive selection resulted in 1 X 10(4) (median) residual CD3(+)-cells/kg (0.7-3x 10(4)). Patients with CD3/CD19-depleted grafts received 3.2x10(4) (median) (0.7-16 x 10(4)) residual T-cells/kg. Those grafts also comprised NK-cells (median number: 86x10(6)/kg), dendritic cells and monocytes/granulocytes. Primary engraftment of the stem cell products was comparable after CD34- and CD133-selection (85 and 72%). In the CD3/CD19 group, 91 % had a primary engraftment. After reconditioning, all patients (64/64) were finally engrafted. Patients with CD34-selected or CD133-selected grafts had similar incidences of a GvHD II-IV (3 and7 %), whereas a GvHD was slightly increased in patients receiving CD3/CD19-depleted cells (27%). Reconstitution of CD3(+) T-cells was faster in the CD3/CD19 group than in the CD34 or CD133 group. These preliminary results indicate, that CD3/CD19-selected grafts may be advantageous regarding engraftment and immunoreconstitution. Since effector cell with potential antileukemic activity are cotransfused, such grafts may be suited in particular for patients with insufficient remission.