Styczynski Jan, Wysocki Mariusz
Department of Pediatric Hematology and Oncology, Medical University Bydgoszcz, Bydgoszcz, Poland.
Pediatr Blood Cancer. 2004 Feb;42(2):195-9. doi: 10.1002/pbc.10457.
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.
复发的小儿急性髓系白血病(AML)患者临床预后较差。本研究旨在分析儿童AML复发时与新诊断AML相比的体外耐药谱。对通过MTT试验检测的98例小儿AML样本结果进行了分析。由于在4天培养中原始细胞自发凋亡、试验开始或结束时样本中髓母细胞百分比低、感染或样本中形成凝块,18个样本(18%)被排除在进一步分析之外。最后,将20例复发样本的体外耐药性与60例初发AML样本进行比较,其中包括9对匹配样本。每位患者最多测试18种药物。在AML诊断时和复发时的耐药性之间,无论是对于整个患者组还是仅对于匹配样本,均未发现显著差异。可能发现复发时髓母细胞对美法仑、噻替派、4 - HOO - 异环磷酰胺和克拉屈滨具有相对较好的敏感性。总之,儿童AML复发时的细胞耐药性不高于首次诊断时。这些观察结果表明,除细胞耐药性外,其他因素在复发儿童AML的治疗失败中起关键作用。