MULTILINEAGE LONG-TERM ENGRAFTMENT POTENTIAL OF DRUG-RESISTANT HEMATOPOIETIC PROGENITORS

Peripheral blood progenitor cells (PBPCs) are increasingly used instea d of bone marrow for autologous or allogeneic transplantation. In this study PBPCs mobilized in cancer patients by chemotherapy and granuloc yte-colony stimulating factor were collected by apheresis and first en riched by immunoaffinity removal of lineage positive cells. When these cells were exposed to both cyclophosphamide and taxol or cultured for 7 days in the presence of 5-fluorouracil, stem cell factor, and inter leukin-3, 88% to 93% of the enriched PBPCs were killed and short-term clonogenic capacity in methylcellulose assays was lost, but week-5 cob blestone area-forming cell (CAFC) enrichment was higher than 10-fold i n comparison to enriched PBPCs and higher than 700-fold in comparison to unmanipulated apheresis cells. After drug exposure, most of the pro genitors displayed a CD34(+), CD38(-), multidrug-resistance (MDR+), Rh odamine 123 low, Hoechst 33342 low phenotype, and as few as 180 of the se drug-resistant cells were able to generate a stable multilineage hu man hematopoiesis in sublethally irradiated immunodeficient mice. In t hese animals, the level of human hematopoietic engraftment was signifi cantly increased by cotransplantation of irradiated cells from the hum an L87/4 stromal cell line. These observations are consistent with the functional isolation of a population of very early hematopoietic prog enitors and might help to design new protocols for the removal of neop lastic cells from autografts. (C) 1997 by The American Society of Hema tology.