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Quantitation of 1-ß-D-Arabinofuranosylcytosine 5'-Triphosphate in the Leukemic Cells from Bone Marrow and Peripheral Blood of Patients Receiving 1-ß-D-Arabinofuranosylcytosine Therapy¹

Department of Developmental Therapeutics, The University of Texas System Cancer Center M. D. Anderson Hospital and Tumor Institute, Houston, Texas 77030

A method for the detection and quantitation of 1-ß-D-arabinofuranosylcytosine 5'-triphosphate (ara-CTP), the active metabolite of 1-ß-D-arabinofuranosylcytosine (ara-C), in the bone marrow cells and leukemic cells of the peripheral blood from patients receiving ara-C therapy is described. ara-CTP is separated from normal cellular nucleotides by high-pressure liquid chromatography and is quantitated by its absorbance of ultraviolet light at 280 nm with a lower limit of sensitivity of 25 pmol/2 x 10⁷ cell equivalents. During separate courses of continuous infusion of different therapeutic doses of ara-C, ara-CTP accumulated in the leukemic bone marrow cells of a patient with acute myelogenous leukemia in proportion to the dose of ara-C. Continuous infusion of ara-C (90 mg/sq m/day) resulted in plateau levels of ara-CTP in peripheral blast cells after 24 hr (115 pmol/1 x 10⁷ cell equivalents). A priming dose of ara-C (125 to 250 mg/sq m) followed by a 1-hr infusion of an equal dose of ara-C to patients with acute myelogenous leukemia facilitated the determination of ara-CTP retention in bone marrow and peripheral blood leukemic cells in vivo. This procedure should be useful for extended studies of the biochemical pharmacology of ara-CTP in vivo.

¹ Supported by NIH Grants CA 14528, CA 11520, and RR-5511; National Cancer Institute Contract CM 87185; and American Cancer Society Grant CH-130.

² To whom requests for reprints should be addressed.

Received 8/ 7/79. Accepted 11/30/79.

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