The Analysis of Correlations between Drug Resistance and Clinical/Laboratory Measures Found in a Group of Children with ALL Treated by ALL-BFM 90 Protocol

Vladimir MIHAL; Marian HAJDUCH; Vera NOSKOVA; Anna JANOSTAKOVA; Maria SAFAROVA; Miroslav OREL; Galina KOUZMINA; Jan STARY; Bohuslav BLAZEK; Dagmar POSPISILOVA



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The Analysis of Correlations between Drug Resistance and Clinical/Laboratory Measures Found in a Group of Children with ALL Treated by ALL-BFM 90 Protocol
Bulletin du Cancer. Volume 91, Number 4, 10080-9, Avril 2004, Electronic Journal of Oncology
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Author(s) : Vladimir MIHAL, Marian HAJDUCH, Vera NOSKOVA, Anna JANOSTAKOVA, Maria SAFAROVA, Miroslav OREL, Galina KOUZMINA, Jan STARY, Bohuslav BLAZEK, Dagmar POSPISILOVA
Summary : This study was designed to assess the predictive value of an MTT (3-[4,5- dimethylthiazol-2,5-diphenyl] tetrazolium bromide) in vitro assay for the evaluation of leukemic cell resistance/sensitivity to cytotoxic drugs, and to compare these results with clinical and laboratory parameters in cases of childhood acute lymphoblastic leukemia (ALL). The chemoresistance of leukemic cells was ascertained by means of an MTT assay in 32 previously untreated children with ALL. The children were treated using the protocol ALL-BFM 90. Statistical correlations were made between in vitro drug resistance to anti-cancer drugs: prednisolone (PRED), vincristine (VCR), daunorubicin (DNR), etoposide (VP-16) and cytosine arabinoside (ARA-C) and in vivo clinical and laboratory parameters: age, sex, risk factor (RF), leukocytes (WBC) and absolute number of blast cells (BC) at diagnosis (BCO), BC at day 8 (BC8), the percentage of blast cells in bone marrow at day 15 (BM15) and at day 33 (BM33), and leukocyte surface antigens CD3, CD4, CD5, CD8, CD10, CD19, CD20, HLA-DR. The results of the study showed a strong correlation between a patient’s drug resistance to PRED, DNR and VCR, supporting an explanation for common mechanisms) of chemoresistance. Moreover, in vitro drug resistance to VCR was positively correlated with the patient’s age and thus was consistent with poor treatment response in older children. However, there was no significant association between patient’s clinical response to glucocorticoids, monitored by decrease in BC within the first week of PRED monotherapy, and in vitro sensitivity to PRED. The reasons for the lack of this expected correlation are discussed. Copyright John Libbey Eurotext 2003.
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