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F Lacombe, F Belloc, P Dumain, M Puntous, PC Makhoul, MC Saux, P Bernard, MR Boisseau and J Reiffers
Laboratoire d'Hematologie, Hopital Haut-Leveque CHU Bordeaux, Pessac,
France.
Cytarabine (Ara-C) is currently used in the treatment of adult acute
myeloid leukemia (AML). To predict the results of induction chemotherapy,
it could be useful to detect leukemic cells that are resistant to Ara-C in
patients with AML. Using a bromodeoxyuridine/DNA (BrdUrd/DNA) staining
method in flow cytometry (FCM), we have developed a cell resistance index
to Ara-C (RI). The technique has been applied to 121 bone marrow (BM)
samples from patients with de novo AML treated by a regimen containing
Ara-C and daunorubicin (DNR). Ninety-seven patients achieved a complete
remission (CR), and 24 patients did not and were considered drug-resistant
(DR). The BM cells collected at diagnosis were cultured for 48 hours and
underwent BrdUrd/DNA analysis. Among 25 patients with no or very low
proliferative activity (<3% of cells in S-phase), the proportion of DR
patients (nine of 25) was significantly higher than in a second group of 96
patients with detectable proliferative activity (15 of 96) (P < .025).
Within this second group, there was a first group of nine patients with
high RI values, which included only DR patients; a second group of 63
patients with low RI values, which included 62 CR patients; and a third
group of 24 patients with intermediate RI values, which included 19 CR and
five DR patients. In view of this series, our results show that it is
possible to detect a majority of DR patients treated by Ara-C.
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