Selective Depletion of Αβ T Cells and B Cells for HLA-Haploidentical Hematopoietic Stem Cell Transplantation. a Three-Year Follow-Up of Procedure Efficiency

HLA-haploidentical family donors represent a valuable option for children requiring allogeneic hematopoietic stem cell transplantation (HSCT). Since graft-versus-host diseases (GvHD) is a major complication of HLA-haploidentical HSCT due to alloreactive T cells in the graft, different methods have been used for ex vivo T-cell depletion. Removal of donor αβ T cells, the subset responsible for GvHD, and of B cells, responsible for post-transplant lymproproliferative disorders, has been recently developed for HLA-haploidentical HSCT. In addition to CD34+ progenitors, this manipulation preserves NK, γδ T and monocytes/dendritic cells, contributing to anti-leukemia activity, and protection against infections. We analyzed depletion efficiency and cell yield in 200 procedures performed in the last 3 years in our center. Donors underwent CD34+ HSC peripheral blood mobilization with G-CSF. Poor CD34+ cell mobilizers (48/189, 25%) received Plerixafor in addition to G-CSF. Aphereses containing a median of 52.5x10(9) nucleated cells and 494x10(6) CD34+ HSC were manipulated using the CliniMACS device. In comparison to the initial product, αβ T-cell depletion produced a median 4.1 log reduction (range 3.1-5.5) and B-cell depletion led to a median 3.4 log reduction (range 2.0-4.7). Graft products contained a median of 18.5x10(6) CD34+ HSC/kg recipient body weight, with median values of residual αβ T cells and B cells of 29x10(3) and 33x10(3)/kg, respectively. Depletion efficiency monitored at 6-month intervals demonstrated steady performance, while improved recovery of CD34+ cells was observed after the first year (p=0.0005). These data indicate that αβ T-cell and B-cell depletion of HSC grafts from HLA-haploidentical donors was efficient and reproducible.