Kaspers Gertjan J L, Wijnands Jelle J M, Hartmann Reinhard, Huismans Loekie, Loonen Anne H, Stackelberg Arend, Henze Guenter, Pieters Robrecht, Hählen Karel, Van Wering Elisabeth R, Veerman Anjo J P
Department of Pediatric Oncology/Hematology, VU University Medical Center, De Boelelaan 1117, NL-1081 HV Amsterdam, The Netherlands.
Eur J Cancer. 2005 Jun;41(9):1300-3. doi: 10.1016/j.ejca.2005.02.026.
At relapse, T-cell acute lymphoblastic leukaemia (ALL) has a worse patient outcome than B-cell precursor (BCP-) ALL. To investigate this further, we compared in vitro cellular drug resistance profiles of T-cell and BCP-ALL samples obtained at relapse. We investigated 237 paediatric relapsed ALL cases, including 151 samples taken at first relapse, of which 30 were T-cell ALL. In vitro drug resistance was measured using the 4-day methyl-thiazol-tetrazolium (MTT) assay and cellular immunophenotype was determined at central reference laboratories. Similar results were found for first relapsed ALL samples and for the total group: T-cell ALL samples were more resistant to 4-HOO-ifosfamide (1.4-fold, P = 0.019) and cisplatin (3.7-fold, P = 0.005). The samples were more sensitive to thiopurines such as mercaptopurine (2.1-fold, P = 0.007) and thioguanine (1.7-fold, P = 0.003). Resistance/sensitivity to 16 other drugs did not differ significantly. These results do not explain the relatively poor prognosis of T-cell ALL at relapse, but do suggest that the more intensive use of thiopurines in relapsed T-cell ALL may be beneficial.
复发时，T细胞急性淋巴细胞白血病（ALL）患者的预后比B细胞前体（BCP-）ALL更差。为了进一步研究这一情况，我们比较了复发时获得的T细胞和BCP-ALL样本的体外细胞耐药谱。我们研究了237例儿童复发ALL病例，包括首次复发时采集的151个样本，其中30个是T细胞ALL样本。使用4天甲基噻唑四氮唑（MTT）法测量体外耐药性，并在中央参考实验室确定细胞免疫表型。首次复发ALL样本和总体组得到了相似的结果：T细胞ALL样本对4-羟基异环磷酰胺（1.4倍，P = 0.019）和顺铂（3.7倍，P = 0.005）的耐药性更强。样本对巯嘌呤和硫鸟嘌呤等硫嘌呤类药物更敏感（分别为2.1倍，P = 0.007和1.7倍，P = 0.003）。对其他16种药物的耐药性/敏感性没有显著差异。这些结果并不能解释复发时T细胞ALL相对较差的预后，但确实表明在复发的T细胞ALL中更密集地使用硫嘌呤类药物可能有益。
