Purging murine leukemic marrow with alkyl-lysophospholipids.
Autologous bone marrow transplantation is potentially curative in the treatment of acute leukemia if residual leukemic cells in the marrow can be eliminated prior to transplantation. We studied the purging effects of a synthetic alkyl-lysophospholipid (ALP) on marrow containing leukemic cells from a transplantable myelomonocytic leukemia (WEHI-3B) in BALB/c mice. Simulated remission bone marrow containing 2% leukemic cells treated in vitro with 20 and 100 micrograms/mL of ET-18-OCH3 (1-octadecyl-2-methyl-sn-glycerol-3-phosphocholine) significantly prolonged survival of lethally irradiated transplanted recipients. At a dose of 100 micrograms/mL, 88% of the mice survived for the duration of the experiment (approximately five months). Autopsies showed that 25% of these survivors had microscopic evidence of leukemia. Thus, in vitro treatment of marrow eliminated leukemic blasts and spared sufficient normal stem cells to allow hematologic reconstitution. The effect of ET-18-OCH3 is not entirely selective for leukemic cells. A spleen colony assay showed that ALP has some cytotoxic effect on normal hematopoietic stem cells.
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects*; D001854:Bone Marrow Cells; D016026:Bone Marrow Transplantation; D003114:Colony-Forming Units Assay; D006086:Graft vs Host Disease / Q000517:prevention & control; D007942:Leukemia, Experimental / Q000401:mortality / Q000628:therapy; D008244:Lysophosphatidylcholines / Q000494:pharmacology*; D008246:Lysophospholipids; D051379:Mice; D010742:Phospholipid Ethers; D010743:Phospholipids / Q000627:therapeutic use
D008244:Lysophosphatidylcholines; D008246:Lysophospholipids; D010742:Phospholipid Ethers; D010743:Phospholipids; C026659:edelfosine