DETECTION OF BLAST CELLS RESISTANT TO ARA -C IN ACUTE MYELOID-LEUKEMIA USING FLOW-CYTOMETRY

Ara-C is currently used in the treatment of adult acute myeloid leukem ia (AML). The cytotoxicity of Ara-C derives from an inhibition of DNA synthesis which can be determined using flow cytometry from the amount of bromodeoxyuridine (BrdUrd) incorporated into cells after a short e xposure to BrdUrd. We developed a computer program to quantify inhibit ion of the rate of DNA synthesis by analysis of the distribution of Br dUrd/DNA. A resistance index (RI) was expressed as the ratio of the am ount of BrdUrd incorporated into S phase cells incubated with Ara-C to that incorporated in the absence of Ara-C. In Ara-C sensitive and res istant HL60 cell lines, a linear relationship between RI and log Ara-C concentration was observed. This technique was applied to 96 bone mar row samples from patients with de novo AML treated by a regimen contai ning Ara-C. A first group of nine patients with high RI values include d only drug resistant (DR) patients; a second group of 63 patients wit h low RI values included 62 patients who achieved a complete remission (CR); a third group of 24 patients with intermediate RI values includ ed 19 CR and five DR patients. In view of these results, we think that it is possible to detect a majority of DR patients treated by Ara-C.