Combined CD34 positive plus CD2 negative selection for effective T-cell depletion as GvHD-prophylaxis in HLA-nonidentical blood progenitor cell transplantation

Abstract

G-CSF mobilized, T-cell-depleted peripheral blood progenitor cells (PBPC) and T-cell-depleted bone marrow (BM) were given to seven children (6 AL, 1 SCID) to prevent severe graft-versus-host-disease (GvHD) as well as graft rejection after transplantation from HLA-nonidentical parental donors. BM was T-cell-depleted by lectin agglutination and E-rosetting. For T-cell-depletion of the PBPC grafts a combination of CD34+ selection with the Ceprate SC® immunoadsorption system and a subsequent depletion of CD2+ cells with immunomagnetic Dynabeads® was used. The overall recovery was 0.3 (0.1–1.2)% for nucleated cells, 29 (18–45)% for CD34+ cells and 0.002 (0–0.015)% for CD3+ cells, respectively. The purity of CD34+ cells was 87 (68–97)% with a 0.3(0.05–0.7)% residual CD3+ T-cell contamination. In spite of the large Tcell number in the PBPC grafts the combination of CD34 positive and subsequent CD2 negative selection achieved a more than 4 log T-cell depletion and prevents severe GvHD even in HLA-nonidentical transplantation. In addition, if a high dose of progenitor cells ensures stable engraftment, this new approach could increase the possibility of wider use of HLA-mismatched family donors for transplantation.