Clinical impact of in vitro cellular drug resistance on childhood acute lymphoblastic leukemia in Taiwan

Despite the successful treatment of childhood acute lymphoblastic leukemia (ALL), the resistance to chemotherapy in ALL cells continues to play an important role in treatment failure. In vitro drug resistance determined using an MTT [3(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay was carried out in 16 children with newly diagnosed ALL between November 2009 and December 2010. The in vitro therapeutic effects of asparaginase, vincristine, prednisolone, dexamethasone, epirubicin and cytarabine were examined. Although there was no significant association between in vitro drug resistance of leukemic cells and ALL subtypes, ETV6-RUNX1 ALL tended to be more sensitive to asparaginase, vincristine and prednisolone. Leukemic cells from girls were significantly more sensitive to epirubicin compared with boys (p = 0.008). Higher leukocyte count at diagnosis was correlated with in vitro resistance to asparaginase and prednisolone (p = 0.03 and 0.05, respectively). Relapse or death occurred in five patients. The leukemic cells from these five patients demonstrated increased in vitro resistance to asparaginase compared to those from the other 11 patients (p = 0.009). From the present case series, the demonstrated in vitro resistance to chemotherapeutic agents may have a prognostic value in children with ALL before comprehensive minimal residual disease measurement is available.