GENERATION OF PROGENITOR-CELL PRECURSORS IN LONG-TERM BONE-MARROW CULTURES AFTER MARROW PURGING WITH ETHER LIPIDS

Alkyl-lysophospholipid derivates (ALP) are currently being tested as b one marrow (BM) purging agents prior to autologous BM transplantation in different malignancies. We evaluated the toxicity of the ALP ET-18- OCH3 (ET-18; Edelfosine, octadecyl-2-0-methyl-rac-glycero-3-phosphocho line) towards early hematopoietic precursors by testing progenitor reg eneration of non-purged and ET-18-purged BM (75 mu g and 125 mu g ET-1 8/ml/2x10(7) BM cells) in autologous long-term bone marrow cultures (L TBMC) from 3 different patients in complete remission. LTBMC feeder la yers were irradiated with 875 rad for complete elimination of hematopo ietic progenitors and recharged with cryopreserved purged and non-purg ed BM. In weekly intervals, adherent layer and supernatant LTBMC cells were completely removed and evaluated in colony forming unit (CFU)-as says. We have seen sufficient CFU-regeneration out of ET-18-purged BM up to 8 weeks of LTBMC (>40 CFU/flask). Total CFU-counts from LTBMC wi th purged BM were slightly reduced compared to non-purged control. Hig h dose purging with 125 mu g ET-18/ml partly inhibited initial CFU-pro liferation, but demonstrated elevated CFU-counts after 4 and 8 weeks o f LTBMC compared to control. In conclusion, in our LTBMC series ET-18- purging yielded tolerable toxicity towards committed BM-progenitors, b ut no remarkable decline of early hematopoietic precursors regeneratin g CFU-progenitors for up to 8 weeks of culture.