A one-step large-scale method for T- and B-cell depletion of mobilized PBSC for allogeneic transplantation

Clinical-scale single-step CD4+ and CD8+ cell depletion for donor innate lymphocyte infusion (DILI)

“…This T-cell depletion efficacy is comparable to strategies using anti-CD3 antibodies on the CliniMACS device. 38,43 For CD3 depletion, a low incidence of GVHD has been reported in the clinical setting (that is, haploidentical transplantation) even without GVD prophylaxis unless T-cell dose exceeded 5 Â 10 4 CD3 þ cells per kg. 38,43 The median processing time for this large-scale CD4/CD8 depletion protocol was only 2-4 h. Similar clinical-scale techniques for depletion of CD4 þ cells and (partial) depletion of CD8 þ cells from bone marrow grafts using a different immunomagnetic method have been described previously.…”

“…38,43 For CD3 depletion, a low incidence of GVHD has been reported in the clinical setting (that is, haploidentical transplantation) even without GVD prophylaxis unless T-cell dose exceeded 5 Â 10 4 CD3 þ cells per kg. 38,43 The median processing time for this large-scale CD4/CD8 depletion protocol was only 2-4 h. Similar clinical-scale techniques for depletion of CD4 þ cells and (partial) depletion of CD8 þ cells from bone marrow grafts using a different immunomagnetic method have been described previously. [44][45][46] However, all these approaches reported a significant lower T-cell depletion efficacy with a significant number of residual CD8 þ T cells in the graft (mean log 10 CD4 þ /8 þ cell depletions ranged around 2) and despite GVHD prophylaxis, acute GVHD was observed after transplantation of these (partially) CD4/CD8 depleted marrow grafts.…”

New strategies for haploidentical transplantation

“…To accelerate the post-transplant immune reconstitution, negative depletion strategies of T-and B-cells were evaluated. The introduction of semiautomated devices for the concomitant depletion of T-and B-lymphocytes to prevent GvHD and post-transplant Epstein-Barr virus-associated lymphoproliferative disease, respectively, allows the effective depletion of CD3 + and CD19 + lymphocytes (CD3/19 depletion) from mobilized peripheral stem cell grafts (8). The T-cell depletion with this method (3.5-4 log) is less as compared with the CD34 + positive selection method (4.5-5 log).…”

“…These include CD34 + positive selection (6), CD3 depletion (7), CD3/ CD19 depletion (8), and TcRαβ/CD19 depletion (9). • Bone marrow (BM) and/or peripheral stem cells can be collected, depending on the preference of the transplant center.…”

Haploidentical haematopoietic stem cell transplantation for acute leukaemia in adults: experience in Europe and the United States

“…34 Consequently, negative selection of G-CSF-mobilized PBPCs (CD3/CD19 depletion with anti-CD3-and -CD19-coated microbeads on a Clinimacs device) was used so as to infuse large numbers of CD34 þ and CD34À cells, CD8 þ T cells, NK cells and other accessory cells. 35 Their current HSCT protocol includes reduced intensity conditioning (RIC)-melphalan, thiotepa and fludarabine-followed by CD3/CD19-depleted PBSCs. OKT3 is used instead of ATG.…”