Ex vivo drug resistance in childhood acute myeloid leukemia on relapse is not higher than at first diagnosis.
Relapsed pediatric patients with acute myeloid leukemia (AML) have a poor clinical prognosis. The aim of this study was the analysis of the ex vivo drug resistance profile on relapse in childhood AML in comparison to newly diagnosed AML. The results of 98 pediatric AML samples tested by the MTT assay were analyzed. Eighteen samples (18%) were excluded from the further analysis due to spontaneous apoptosis of blasts in 4-days culture, low percentage of myeloblasts in the sample either in the beginning or at the end of the assay, infection, or formation of clots in the sample. Finally, ex vivo drug resistance of 20 relapsed samples were compared with that of 60 de novo AML, including 9 matched pairs. Up to 18 drugs were tested for each patient. No significant differences between drug resistance at diagnosis and at relapse in AML was found, neither for the whole groups of patients, nor for matched pairs only. Possibly, relatively good sensitivity of myeloblasts on relapse was found against melphalan, thiotepa, 4-HOO-ifosfamide, and cladribine. In summary, cellular drug resistance in childhood AML at relapse is not higher than at first diagnosis. These observations suggest that other, than cellular drug resistance, factors play a key role in therapy failure of relapsed childhood AML.
Styczynski
Jan
J
Department of Pediatric Hematology and Oncology, Medical University Bydgoszcz, Bydgoszcz, Poland. jan_styczynski@wp.pl
Wysocki
Mariusz
M
D000208:Acute Disease; D000293:Adolescent; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002455:Cell Division / Q000187:drug effects; D002648:Child; D002675:Child, Preschool; D020732:Cytogenetic Analysis; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007951:Leukemia, Myeloid / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics
D000970:Antineoplastic Agents