CHANGES IN THE FUNCTIONAL-CAPACITY OF MARROW STROMAL CELLS AFTER AUTOLOGOUS BONE-MARROW TRANSPLANTATION

Marrow stromal cells were evaluated several months after autologous BM T for their capacity to support both normal hemopoiesis and secrete th e main growth factors involved in its control, G-CSF, GM-CSF, IL-3 and SCF. Stromal layers (SL) were obtained by long-term marrow cultures ( LTMC) established from 15 patients (9 with hematologic malignancies an d 6 with solid tumors) 3 months after autologous BMT and were compared to pre-graft patients. After irradiation, both post-graft and pre-gra ft SL were recharged with the same inoculum of normal marrow cells. As compared to pre-graft values, CFU-GM production on post-graft SL was significantly increased during the first 2 weeks of culture whereas it was decreased from week 3 to week 8. These findings were only observe d in patients with hematologic malignancies and not in patients with s olid tumors. Growth factor secretion was evaluated by ELISA in the sup ernatants of unstimulated and IL-1-stimulated SL from 10 post-graft pa tients, 13 pre-graft patients and 5 normal controls. In any group of p atients, IL-3 was undetectable either spontaneously or after IL-1-stim ulation. As compared to controls, secretion by IL-1-stimulated SL was not different for GM-CSF in pre- and post-graft patients but tended to be decreased for G-CSF in post-graft patients. SCF secretion, which w as not induced by IL-1, appeared dramatically decreased in both pre-an d post-graft patients. The capacity of post-graft SL to support CFU-GM growth in LTMC was correlated at week 1 with G-CSF secretion and from week 3 to week 8 with SCF secretion. These results suggest that micro environment remains qualitatively damaged several months after BMT inv olving a decreased capacity both to support early hemopoiesis and to s ecrete SCF, particularly in patients grafted for hemopoietic malignanc ies.