In vitro drug sensitivity and apoptosis induction in newly diagnosed pediatric acute lymphoblastic leukemia: correlation with overall survival

Pediatr Hematol Oncol. 2004 Sep;21(6):465-73. doi: 10.1080/08880010490477239.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / pharmacology*
  • Apoptosis / drug effects*
  • Child
  • Child, Preschool
  • Drug Screening Assays, Antitumor
  • Female
  • Humans
  • Infant
  • Male
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / mortality
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology