Allogeneic transplantation of CD34+ selected hematopoietic cells--clinical problems and current challenges

Since G-CSF mobilized peripheral blood has become the major source of hematopoietic cells (PBSC) for allogeneic transplantation of patients with hematological malignancies, new technologies of T-cell depletion were developed to reduce the risk of graft-versus-host disease. CD34+ selection by immunomagnetic separation has been shown to be the most effective method to achieve a 3-4 log depletion of T-cells while preserving the high number of hematopoietic progenitors in the graft. The high number of CD34+ cells contained in the positive fraction have allowed to facilitate engraftment from sibling donors matched for only one haplotype. In addition, studies in pediatric recipients have shown that high numbers of hematopoiteic progenitors infused can lead to timely recovery of T- and B-cells in the first year after transplantation. Positive results have also been reported in patients with chronic myelogenous leukemia who had received CD34+ selected PBSC from HLA-identical sibling donors and subsequent infusions of donor T-cells to establish graft-versus-leukemia effects. On the other hand, studies performed in adults with advanced leukemia receiving CD34+ selected PBSC from haploidentical or unrelated donors demonstrated an increased risk for graft-rejection, relapse and late opportunistic infections. Future efforts will have to concentrate on the restoration of cellular immunity by either adaptively transferring antigen specific effector cells or by studying the use of cytokines like interleukin-7. Although these question have not been resolved yet, allogeneic transplantation of highly purified CD34+ PBSC has become an therapeutic option for patients who are at high-risk for severe GvHD.