IN-VITRO RESISTANCE TO CYTOSINE-ARABINOSIDE, NOT TO DAUNORUBICIN, IS ASSOCIATED WITH THE RISK OF RELAPSE IN DE-NOVO ACUTE MYELOID-LEUKEMIA

The efficacy of chemotherapy in acute myeloid leukaemia (AML) is limit ed by clinical drug resistance. We determined in vitro resistance to c ytosine arabinoside (ARAC), daunorubicin (DNR), mitoxantrone (MITOX), m-amsacrine (AMSA) and etoposide (VP16) in 49 adults with de novo AML using the MTT assay. Results showed that nonresponders to chemotherapy were, in vitro, 2 . 9-fold more resistant to DNR, but not more resist ant to ARA-C, compared to complete responders. However, complete respo nders who were in vitro resistant to ARA-C had a 4-fold higher risk of relapse (95% CI 1 . 3-12 . 5-fold) compared to complete responders in vitro sensitive to ARA-C. With a mean follow-up of 12 months the prob ability of continuous complete remission (CCR) for patients in vitro s ensitive to ARA-C was 61% at 34 months (95% CI 28-82%), whereas all pa tients in vitro resistant to ARA-C relapsed within 18 months from diag nosis. This difference appeared to be independent of other clinical fe atures such as sex, age, white blood cell count, FAB classification, a nd CD34 expression. In vitro resistance to DNR was not related to the probability of CCR. We conclude that in vitro drug resistance assessed with the MTT assay appears to be associated with short- and long-term clinical outcome in AML. Confirmatory studies comprising a sufficient number of patients for multivariate analyses should prove whether in vitro resistance to ARA-C will appear to be an independent risk factor .