IN-VITRO CELLULAR-DRUG RESISTANCE IN CHILDREN WITH RELAPSED REFRACTORY ACUTE LYMPHOBLASTIC-LEUKEMIA/

Cellular drug resistance is thought to be an important cause of the po or prognosis for children with relapsed or refractory acute lymphoblas tic leukemia (ALL), but it is unknown when, to which drugs, and to wha t extent resistance is present, We determined in vitro resistance to 1 3 drugs with the MTT assay, Compared with 141 children with initial AL L, cells from 137 children with relapsed ALL were significantly more r esistant to glucocorticoids, L-asparaginase, anthracyclines, and thiop urines, but not to vinca-alkaloids, cytarabine, ifosfamide, and epipod ophyllotoxins. Relapsed ALL cells expressed the highest level of resis tance to glucocorticoids, with a median level 357- and >24-fold more r esistant to prednisolone and dexamethasone, respectively, than initial ALL cells, whereas the resistance ratios for the other drugs differed from 0.8- to 1.9-fold. Intraindividual comparisons between initial an d relapsed samples from 16 children with ALL showed that both de novo and acquired drug resistance were involved, Specific in vitro drug-res istance profiles were associated with high-risk relapsed ALL groups. I n vitro drug resistance was also related to the clinical response to c hemotherapy in relapsed/refractory childhood ALL, We conclude that dru g resistance may explain the poor prognosis for children with relapsed /refractory ALL, These data may be helpful to design alternative treat ment regimens for relapsed childhood ALL. (C) 1995 by The American Soc iety of Hematology.