Acute Leukemia Susceptibility Testing And Clinical Application

Purpose To study the correlation between the results of the MTT combined chemosensitivity test and the clinical effects of 5 kinds of combined chemotherapy regimens in acute leukemia(AL) and to study whether the MTT assay can be used to study drug interaction in vitro in AL samples or not, and the correlation between the results of the MTT combined chemosensitivity in vitro or in vivo and the drug interactions in vitro. Methods We studied Five drug combinations, Each at 5 concentrations, with MTT assay in AL samples from 53 AL patients at initial or relapsed diagnosis. In vitro sensitivity was defined as a LCS lower than 30%. In vivo sensitivity was defined as complete remission (CR) or marrow blast cell declined index(MBDI) equal to or higher than 60%. And we used the ultiplicative?Model and the aximum?model to classify each observation for a drug combination as being either a synergistic, additive, or antagonistic interaction. Results (1) There were 18 S(sensitive)/S, 11 R(resistant)/R, 2 SIR., 1R/S (in vitro/in vivo) in 32 Patients. The general, Positive and negative coincident rates of in vitro with in vivo, specificity and sensitivity were 90. 6%, 90%, 91. 7%, 84. 6% and 94. 7%, respectively. (2) We observed a marked heterogeneity in drug interactions between patients, between combinations and between different concentrations within one specific combination. Between Homoharringtonine (HHT) and cytosine arabinoside (Ara), Synergism was found in 16. 4%, antagonism in 14. 5%, additivity in 69% of the 110 observations. Between daunorubicin (DNR)+Ara, synergism was found in 21.8%, antagonism in 16.4%, additivity in 61.8% of the 110 observations. Between mitoxantrone (MTZ)+Ara, synergism was found in21. 8%, antagonism in 18. 7%, additivity in 60% of the 110 observations. (3)The Sensitive drug combinations in vitro all showed additive and synergistic interactions at cutff comcentrations. Conclusion (l)The results of the MTT combined chemosensitivity test were well correlated with the clinical responses of combined chemotherapy regimens. (2)The MTT assay can be used to study drug interactions in vitro in AML samples. (3)The type of interaction was different between patients, and depends on the drug combination and concentrations. (4)The combinations HUT+Ara. DNR+Ara... MTZ+Ara generally showed additive and even synergistic interactions. (5) Direct comparison of the sensitive combinatiQn and the sensitive and synergistic or additive combination with clinical outcome demonstrated no difference in the ability to predict drug resistance, both of themwere well correlated with clinical outcome.