IN-VITRO ANTHRACYCLINE CROSS-RESISTANCE PATTERN IN CHILDHOOD ACUTE LYMPHOBLASTIC-LEUKEMIA

Daunorubicin (DNR) is a major front-line drug in the treatment of chil dhood acute lymphoblastic leukaemia (ALL). Previously, we showed that in vitro resistance to DNR at diagnosis is related to a poor long-term clinical outcome in childhood ALL and that relapsed ALL samples are m ore resistant to DNR than untreated ALL samples. In cell line studies, idarubicin (IDR), aclarubicin (ACR) and mitoxantrone (MIT) showed a ( partial) lack of cross-resistance to the conventional anthracyclines D NR and doxorubicin (DOX), but clinical studies in childhood ALL have b een inconclusive about the suggested lack of cross-resistance. In the present study we determined the in vitro cross-resistance pattern betw een DNR, DOX, IDR, ACR and MIT in 48 untreated and 39 relapsed samples from children with ALL using the MTT assay, The relapsed ALL group wa s about twice as resistant to DNR, DOX, IDR, ACR and MIT as the untrea ted ALL group. Thus, resistance developed to all five drugs. We found a significant cross-resistance between DNR, DOX, IDR, ACR and MIT, alt hough in some individual cases in vitro anthracycline cross-resistance was less pronounced. We conclude that IDR, ACR and MIT cannot circumv ent in vitro resistance to DNR in childhood ALL. Clinical studies may still prove whether IDR, ACR or MIT has a more favourable toxicity pro file than DNR.