Risk-based treatment strategies have improved outcome in childhood B-precursor
acute lymphoblastic leukemia, and in vitro
drug sensitivity assessment using methyl-thiazol-tetrazolium (MTT) assay has been shown to be an independent prognostic marker. To date, such strategies in childhood T-cell
acute lymphoblastic leukemia (
T-ALL) have proved elusive, and in vitro
drug sensitivity testing has had limited success in
T-ALL due to poor T-cell lymphoblast survival in vitro. We have developed the flow cytometric
drug sensitivity assay (FCDSA) to evaluate in vitro
drug sensitivity. We studied 68 cases of childhood
T-ALL for
cytarabine (
Ara-C) and
daunorubicin sensitivity by FCDSA and compared the results with those obtained by MTT assay. Spontaneous apoptosis was correlated with cytotoxicity rates for both drugs by FCDSA, but not with the results obtained by MTT assay.
Daunorubicin sensitivity had a positive correlation with
Ara-C in individual cases by FCDSA; but not by MTT assay. Studies repeated on stored samples had comparable results for both drugs by FCDSA (P<0.01), but not for
Ara-C by MTT assay. Comparison of
T-ALL sensitivity with
acute myeloid leukemia (AML) cases revealed a unique pattern difference. Median cytotoxicity (expressed in arbitrary units) for
Ara-C was 8 (0-47) and 27 (0-81), and daunorubicine cytotoxicity for
T-ALL and AML samples was 79 (5-100) and 34 (0-98), respectively. Although age or white blood cell count at diagnosis was not associated with any particular
drug response pattern, CD13 expression on T-lymphoblasts was associated with in vitro resistance. FCDSA is a reliable, practical and reproducible method that can be integrated into studies of
drug-target cell interactions in
T-ALL.