Developments in Purging in Autotransplantation

Blood Cell Biochemistry

“…Although a number of studies continue to examine gene marking of whole bone marrow, the majority have targeted peripheral blood stem cells or bone marrow cells selected on the basis of CD34 antigen expression (Baum et ai., 1992;Cassel et ai., 1993;Schiller et ai., 1995; as discussed later. Because CD34 cell selection reduces contaminating tumor cells (Freedman and Nadler, 1993;Gazitt et ai., 1995;Vescio et ai., 1994), the likelihood of detecting gene marked tumor cells at relapse is lower in certain trials incorporating this step .…”

“…In eleven patients who had breast cancer or myeloma, CD34+ cells were isolated from bone marrow or peripheral blood and retrovirally marked. The positive selection of CD34+ hematopoietic stem cells is an attractive alternative to purging tumor cells in ABMT for cancer patients (Freedman and Nadler, 1993;Vescio et at., 1994). Purification of CD34+ cells from the marrow or peripheral blood may be particularly valuable in breast cancer or myeloma in which tumor cells do not, on the whole, express CD34.…”

“…Previous attempts to remove tumor cells have focused on tumor depletion by cytotoxic agents, predominantly mafosfamide and 4hydroperoxycyclophosphamide (4HC) , but cytokines, such as IL-2, monoclonal antibodies to B cells, neuroblastoma cells (with or without complement lysis), and more recently photodynamic purging, have all been explored (Freedman and Nadler, 1993). Although such approaches certainly deplete tumor cells without significantly affecting the hematopoietic content of the graft, it is unlikely that this depletion is absolute (Gribben et at., 1991).…”

“…Together with retrospective molecular studies in the mature B cell malignancy, low grade lymphoma (Gribben et al, 1991), the trials described have convinced investigators at many transplant centers that an uncontaminated or successfully purged bone marrow should be used for reinfusion (Freedman and Nadler, 1993;Vescio et at., 1994). Despite this, there is also evidence in some malignancies that purging is unlikely to be efficacious until superior treatment regimens are adopted.…”

Peripheral Blood Stem Cells Differ from Bone Marrow Stem Cells in Cell Cycle Status, Repopulating Potential, and Sensitivity Toward Hyperthermic Purging in Mice Mobilized with Cyclophosphamide and Granulocyte Colony-Stimulating Factor

“…Hence, whatever the source of autologous stem cells, contamination with malignant cells is likely and necessitates the use of in vitro purging techniques for the optimal therapeutic response to an autologous stem cell transplantation (29,30). A variety of purging modalities have been applied to deplete the residual malignant cells in the transplant (31)(32)(33)(34). In previous studies, we and others have demonstrated the feasibility of hyperthermia as a potential physical purging modality in the treatment of hematopoietic malignancies (35)(36)(37)(38)(39).…”