Transplantation of stem cells enriched by immunoadsorption.
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
D F Kalamasz
Publications and source records attributed to D F Kalamasz.
Engraftment after infusion of CD34+ marrow cells in patients with breast cancer or neuroblastoma.
The CD34 antigen is expressed by 1% to 4% of human and baboon marrow cells, including virtually all hematopoietic progenitors detectable by in vitro assays. Previous work from our laboratory has shown that CD34+ marrow cells can engraft lethally irradiated baboons. Because the CD34 antigen has not been detected on most solid tumors, positive selection of CD34+ cells may be used to provide marrow cells capable of engraftment, but depleted of tumor cells. In seven patients with stage IV breast cancer and two patients with stage IV neuroblastoma, 2.5 to 17.5 x 10(9) marrow cells were separated by immunoadsorption with the anti-CD34 antibody 12-8 and 50 to 260 x 10(6) positively selected cells were recovered that were 64 +/- 16% (range 35% to 92%) CD34+. The patients received 1.0 to 5.2 x 10(6) CD34-enriched cells/kg after marrow ablative therapy. Six patients engrafted, achieving granulocyte counts of greater than 500/mm3 at 34 +/- 10 (range 21 to 47) days and platelets counts of greater than 20,000/mm3 at 46 +/- 14 (range 28 to 66) days posttransplant. Five of these patients showed durable engraftment until the time of death 82 to 386 days posttransplant. One patient failed to sustain engraftment associated with metastatic marrow disease. Three patients died at days 14, 14, and 17 posttransplant, two of whom had evidence of early engraftment. These studies suggest that CD34+ marrow cells are capable of reconstituting hematopoiesis in humans.
Antigens, CD↗
Stem cell selection--clinical experience.
The ability to isolate large numbers of hematopoietic progenitors will facilitate an understanding of the growth and differentiation of bone marrow. Furthermore, isolating hematopoietic progenitors will have widespread clinical applications to autologous marrow transplantation, allogeneic marrow transplantation, gene therapy, and in vitro marrow expansion. With the development of avidin-biotin immunoadsorption, it is now feasible to isolate large numbers of these progenitor cells for clinical purposes. Successful hematopoietic reconstitution has been demonstrated in lethally irradiated baboons transplanted with CD34+ cells isolated by immunoadsorption with the anti-CD34 antibody 12-8. Recent studies have shown that CD34+ cells enriched from the marrow of patients with metastatic breast cancer can be used for autologous marrow transplantation.
Animals↗
Positive selection of hematopoietic progenitors from marrow and peripheral blood for transplantation.
The ability to obtain large numbers of purified hematopoietic progenitors (HPC) will facilitate the understanding of elements that influence the growth and differentiation of bone marrow. Furthermore, HPC isolation will have direct application to autologous marrow transplantation (AMT) for malignancies as well as facilitate the transfer of genes in marrow cells for the correction of genetic disorders. The transplantation of HPC will help delineate the cells or factors responsible for graft rejection and graft-versus-host-disease. Or several techniques that have been utilized for the separation of HPC, only the avidin-biotin immunoadsorption (ABIA) method has been shown capable of separating the number of cells required for large animals and man. The application of this technique to AMT in man requires the identification of an antigen found predominantly on HPC in peripheral blood or marrow but not on malignant cells that could potentially contaminate bone marrow. Studies have demonstrated that the CD34 antigen is expressed by the majority of human marrow HPC measured in long-term marrow culture and is expressed on cells capable of autologous engraftment in lethally irradiated baboons. Although the CD34 antigen is not detectable by FACS analysis on peripheral blood cells, ABIA can enrich for such cells. The CD34 antigen is not detected on cells from patients with breast cancer or neuroblastoma thus allowing clinical studies to proceed. Preliminary results suggest that CD34(+)-enriched cells are depleted of tumor cells and are capable of autologous reconstitution in man.
Antigens, CD↗