INCREASED HEMATOPOIETIC PROGENITOR-CELL MAINTENANCE IN LONG-TERM BONE-MARROW CULTURES CONTAINING MINIMAL NUMBERS OF CONTAMINATING BREAST-CANCER CELLS

The maintenance of hematopoietic progenitor cells as assayed in the mi xed colony (CFU-GEMM) assay in human long-term bone marrow cultures wa s compared between normal allogeneic marrow transplantation donor coll ections and those from candidates for high-dose therapy and autologous bone marrow transplantation (ABMT). To be eligible for ABMT, patients were required to have a histologically normal appearing bone marrow a nd therefore any tumor contamination was at minimal levels and detecta ble only after evaluation of the cultured harvests. Marrow from 15 nor mal donors, 36 patients with breast cancer, and 30 patients with Hodgk in's disease was evaluated. The number of mononuclear cells placed in culture was standardized. In all groups, significantly more progenitor cells were recovered at 4-6 weeks of culture than at 12-14 weeks. At 4-6 and 12-14 weeks, there were no significant differences in the numb er of progenitor cells recovered from the cultures of normal donors an d tumor negative cultures of breast cancer or Hodgkin's disease patien ts. However, following 4-6 and 12-14 weeks of culture, progenitor cell numbers of cultures which contained breast cancer cells were signific antly higher than the pooled values for cultures from the concurrent n ormal controls, and those from breast cancer and Hodgkin's disease pat ients with tumor negative cultures. These results suggest that minimal breast cancer cell contamination of the bone marrow can influence the production of marrow progenitor cells. Exposure to prior chemotherapy or radiation therapy does not appear to be the cause of this effect. The most likely mechanism is the local production of cytokines by the tumor cells, although a process involving direct adhesive contact of t he tumor cells with hematopoietic cells, which is sometimes observed i n semisolid cultures, cannot be excluded.