Cellular drug resistance profiles in childhood acute myeloid leukemia: differences between FAB types and comparison with acute lymphoblastic leukemia

Determining in vitro drug resistance may reveal clinically relevant informa tion in childhood leukemia. Using the methyl-thiazol-tetrazolium assay, the resistance of untreated leukemic cells to 21 drugs was compared in 128 chi ldren with acute myeloid leukemia (AML) and 536 children with acute lymphob lastic leukemia (ALL). The differences between 3 French-American-British (F AB) types (M1/M2, M4, and M5) were also compared. AML was significantly mor e resistant than ALL to the following drugs, as noted by the median resista nce: glucocorticoids (greater than 85-fold), vincristine (4.4-fold), L-aspa raginase (6.9-fold), anthracyclines (7.8- to 3.4-fold), mitoxantrone (2.6-f old), etoposide (4.9-fold), platinum analogues (2.4- to 3.4-fold), ifosfami de (3.5-fold), and thiotepa (3.9-fold). For cytarabine and thiopurines, the median LC50 values (the drug concentration that kills 5% of the cells) wer e equal. Also, busulfan, amsacrine, teniposide, and vindesine showed no sig nificant differences, but the numbers were smaller, and the median LC50 val ues were 1.3- to 5.2-fold higher in AML. None of the drugs demonstrated gre ater cytotoxicity in AML. FAB M5 was significantly more sensitive than FAB M4 to most drugs frequently used in AML, as indicated by the following rati os of median sensitivities: the anthracyclines (2.6- to 3.2-fold), mitoxant rone (12.5-fold), etoposide (8.7-fold), and cytarabine (2.9-fold). For etop oside and cytarabine (5.4- and 3.4-fold, respectively) FAB M5 was also sign ificantly more sensitive than FAB M1/M2. FAB M5 was equally sensitive to L- asparaginase and vincristine as ALL. Only 15% of the AML samples were "inte rmediately" sensitive to glucocorticoids, mainly in FAB M1/M2. The poorer p rognosis of childhood AML is related to resistance to a large number of dru gs. Within AML, FAB M5 had a distinct resistance pattern. These resistance profiles may be helpful in the rational design of further treatment protoco ls. (C) 2000 by The American Society of Hematology.