Effects on Human Peripheral Lymphocytes of in Vivo Administration of 9-ß -D-Arabinofuranosyl-2-fluoroadenine-5'-monophosphate (NSC 312887), a New Purine Antimetabolite

摘要: 9-β-d-Arabinofuranosyl-2-fluoroadenine-5′-monophosphate (NSC 312887) (2-F-ara-AMP) is a new purine antimetabolite with documented preclinical activity against number of animal tumors. Data from in vitro studies and toxicology trials indicated that 2-F-ara-AMP might be lymphocytotoxic. We studied effects on peripheral lymphocytes patients receiving the agent Phase I clinical trial. Eleven received 13 courses given by i.v. bolus daily for 5 days. Mononuclear cells were isolated, lymphocyte subsets quantitated immunofluorescence flow cytometry 1 day before treatment 4 hr after final infusion. Lymphocytopenia developed rapidly (median time to nadir, 6 days) was reversible. Standard leukocyte counts, differential percentages isolated mononuclear reactive monoclonal antibodies used calculate numbers each major lymphoycte subpopulation. Total T-lymphocyte counts fell during all courses, calculated mean absolute T-cell decreasing 90%. Decreases observed subsets. By contrast, B-lymphocyte decreased an average 50% noted increase two cycles. also compared recoveries subpopulation administration 2-F-ara-AMP. Recoveries total cells, T-cells, non-T-, non-B-cells reduced substantially 2-F-ara-AMP, but B-cell recovery not reduced. These vivo data, first human subjects, are agreement halopurine nucleotide analogues which have demonstrated T-cells more sensitive than B-cells cytotoxic these compounds.