Bone Marrow Purging in Acute Leukemia with Alkyl-Lysophospholipids: A New Family of Anticancer Drugs

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Abstract
The alkyl-lysophospholipids are a new family of anticancer drugs which target the cell membrane as their site of action. Enzymes involved in signal transduction (protein kinase C and phosphatidylinositol phospholipase C), phospholipid biosynthesis (lysophosphatidyl acyltrans-ferase and CTPcholinephosphate cytidylyltransferase) and maintenance of membrane integ rity (Na, K ATPase sodium pump) are inhibited. A unique feature of the alkyl-lysophospholipids is their selective cytotoxicity to neoplastic cells. This suggests that the compound would be an excellent agent for purging residual leu-kemic cells from marrows of patients in remission prior to autologous bone marrow trans plantation. Preclinical studies in a murine leukemia model and in an in vitro human system demonstrated successful elimination of leukemic cells from a mixture of normal and leukemic marrows. Twenty-nine poor risk patients with acute leukemia underwent autologous bone marrow transplantation and were reinfused with marrow treated in vitro with edelfosine. Nine of these patients remain in remission free of leukemia from 368 to 1369 days. These en couraging results warrant further investigation.