title: In vitro drug sensitivity and apoptosis induction in newly diagnosed pediatric acute lymphoblastic leukemia: correlation with overall survival.
abstract: The present study looked for any associations between in vitro drug sensitivity and clinical outcome in pediatric acute lymphoblastic leukemia (ALL) with the standard drugs used for leukemia therapy. A total of 72 samples were analyzed. In vitro sensitivity to drugs was tested by a methylthiazol-tetrazolium assay in 6 serial fold dilutions. Apoptosis was determined by TUNEL assay and apoptotic index was calculated for each sample. Patients sensitive to prednisone, asparginase, vincristine, and 6-mercapto purine had higher overall survival compared to patients whose tumor cells were resistant to these drugs (p < .01). For the other drugs tested, overall survival did not vary from that of the resistant patients. For doxorubicin, asparginase, vincristine, prednisone combination sensitivity, there was a significant worsening of prognosis from the extremely sensitive patients through an intermediate sensitive group to a most resistant group. The present study thus shows that in vitro drug-sensitivity testing provides significant prognostic information in childhood ALL.
authors.affiliation: Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, India.
authors.forename: G
authors.initials: G
authors.lastname: Srinivas
authors.forename: P
authors.initials: P
authors.lastname: Kusumakumary
authors.forename: Thomas
authors.initials: T
authors.lastname: Joseph
authors.forename: M Radhakrishna
authors.initials: MR
authors.lastname: Pillai
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002648:Child; D002675:Child, Preschool; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology