title: A cell culture model for the treatment of acute myeloblastic leukemia with fludarabine and cytosine arabinoside.
abstract: The purpose of this paper was to ascertain whether results obtained in cell cultures of AML clonogenic blast cells would provide a useful model for a clinical regimen that combines fludarabine (F-ara-AMP) and cytosine arabinoside (ara-C). In the cultures the nucleoside F-ara-A was used. Blast cells from the continuous lines OCI/AML-2 and OCI/AML-3 were grown, either in methylcellulose to quantify clonogenic cells, or in suspension to measure self-renewal as reflected in changes in numbers of clonogenic cells. F-ara-A, like ara-C, was found to be more toxic to blast stem cells in suspension than in the clonogenic assay, indicating that F-ara-A might, in addition to general cytotoxicity, have some specific inhibitory effects on self-renewing stem cells. F-ara-A was less cytotoxic than ara-C; but, when F-ara-A was given before ara-C, synergism was seen at some F-ara-A doses, as manifested by increased ara-C cytotoxicity. In contrast, when ara-C was given before F-ara-A, protection was observed. Control experiments make it unlikely that this effect is related to changes in the cell cycle following ara-C exposure. We conclude that the cellular studies reported here confirm previous pharmacological data indicating that F-ara-A before ara-C increases the effectiveness of ara-C by increasing the accumulation of ara-CTP. However the present experiments show that the synergism between F-ara-A and ara-C is dependent on both dose and schedule.
authors.affiliation: Division of Laboratory Medicine, U.T. M.D. Anderson Cancer Center, Houston 77030.
authors.forename: C
authors.initials: C
authors.lastname: Rayappa
authors.forename: E A
authors.initials: EA
authors.lastname: McCulloch
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage; D002470:Cell Survival; D002478:Cells, Cultured; D003561:Cytarabine / Q000008:administration & dosage*; D004334:Drug Administration Schedule; D004357:Drug Synergism; D006801:Humans; D066298:In Vitro Techniques; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy*; D008747:Methylcellulose; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives*
chemical_list: D000970:Antineoplastic Agents; D003561:Cytarabine; D008747:Methylcellulose; D014740:Vidarabine; C024352:fludarabine