Bm. Zimmer et al., GENERATION OF PROGENITOR-CELL PRECURSORS IN LONG-TERM BONE-MARROW CULTURES AFTER MARROW PURGING WITH ETHER LIPIDS, International journal of oncology, 7(6), 1995, pp. 1307-1313
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.