Evaluation of cytotoxicity by flow cytometric drug sensitivity assay in childhood T-cell acute lymphoblastic leukemia

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...

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Bibliographic Details
Published in:Leukemia & lymphoma 2005-06, Vol.46 (6), p.833-841
Main Authors: Sava an, Süreyya, Buck, Steven, Özdemir, Öner, Hamre, Merl n, Asselin, Barbara, Pullen, Jeannette, Ravindranath, Yaddanapudi
Format: Article
Language:English
Subjects:
Apoptosis
Bone Marrow Cells - cytology
Bone Marrow Cells - metabolism
Child
Daunorubicin - pharmacology
Drug Screening Assays, Antitumor
drug sensitivity
flow cytometry
Flow Cytometry - methods
Humans
Immunophenotyping - methods
Inhibitory Concentration 50
Leukemia, T-Cell - diagnosis
Leukemia, T-Cell - drug therapy
lymphoblastic leukemia
Medical Oncology - methods
MTT
Precursor Cell Lymphoblastic Leukemia-Lymphoma - diagnosis
Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy
Reproducibility of Results
Sensitivity and Specificity
T-cell
Tetrazolium Salts - pharmacology
Thiazoles - pharmacology
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Summary: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
ISSN:1042-8194
1029-2403
DOI:10.1080/10428190500079951