IN-VITRO CELLULAR-DRUG RESISTANCE AND PROGNOSIS IN NEWLY-DIAGNOSED CHILDHOOD ACUTE LYMPHOBLASTIC-LEUKEMIA

As an important determinant of the response to chemotherapy, measureme nts of cellular drug resistance may provide prognostically significant information, which could be useful for optimal risk-group stratificat ion. The objective of this report is to determine the relation between in vitro resistance to 12 drugs, measured with the calorimetric methy lthiazol-tetrazolium (MTT) assay, and long-term clinical response to c hemotherapy in 152 children with newly diagnosed acute lymphoblastic l eukemia. At risk-group stratified analyses, in vitro resistance to pre dnisolone, L-asparaginase, and vincristine were each significantly (P <.01) related to the probability of disease-free survival (pDFS) after combination chemotherapy. The combination of data for prednisolone, L -asparaginase, and vincristine provided 8 drug-resistance profile with prognostic independent significance superior to that of any single dr ug or any other factor. The 3-years pDFS was 100% for the group with t he most sensitive profile, 20% of all patients, 84% (SE 6%) for the gr oup with an intermediately sensitive profile, 40% of all patients, and 43% (SE 8%) for the remaining group with the most resistant profile ( P <.001). In conclusion, the extent of in vitro cellular resistance to prednisolone. L-asparaginase, and vincristine, measured using the MTT assay, was significantly related to the clinical response to combinat ion chemotherapy. Treatment failure in newly diagnosed childhood ALL c an be predicted based on cellular drug resistance data. (C) 1997 by Th e American Society of Hematology.