IN-VITRO CHEMOSENSITIVITY ASSESSED WITH THE MTT ASSAY IN CHILDHOOD ACUTE NONLYMPHOBLASTIC LEUKEMIA

Cellular drug resistance is supposed to play a major role in chemother apy failures which frequently occur in childhood acute non-lymphoblast ic leukemia (ANLL). Therefore, we determined in vitro chemosensitivity to daunorubicin, doxorubicin, mitoxantrone, B-thioguanine, etoposide, and cytosine arabinoside (Ara-C) in childhood ANLL using the colorime tric MTT assay. The 4-day MTT assay was successfully performed in 62/7 3 samples obtained from 53 children with ANLL. We obtained comparable results from bone marrow or peripheral blood samples, and from fresh o r cryopreserved samples. In vitro chemosensitivity was not related to clinical features such as sex, age, white blood cell count, or FAB-typ es. The group of poor responders to chemotherapy was median 8-fold mor e resistant to Ara-C than the group of good responders, but identifica tion of a threshold for Ara-C sensitivity predictive for individual re sponses was limited due to the great overlap of in vitro chemosensitiv ities between both groups. Children with relapsed ANLL were in vitro m edian 3-fold more resistant to Ara-C than the initial ANLL group. No s ignificant differences for the other drugs were observed with respect to clinical response or disease status. These results suggest that in vitro resistance to Ara-C plays an important role in chemotherapy fail ures in childhood ANLL, but larger studies are necessary to establish the predictive value of Ara-C sensitivity assessed with the MTT assay.