Lancaster D L, Patel N, Lennard L, Lilleyman J S
Imperial Cancer Research Fund Children's Cancer Group, Barts and the London School of Medicine, The Royal London Hospital, Whitechapel, London E1 1BB, UK.
Cancer Chemother Pharmacol. 2002 Jul;50(1):33-6. doi: 10.1007/s00280-002-0442-6. Epub 2002 Apr 27.
The aim of this study was to compare leucocyte and erythrocyte thioguanine nucleotide (TGN) cytotoxic metabolite concentrations in children with lymphoblastic leukaemia taking mercaptopurine (MP) or thioguanine (TG) as part of their long-term remission maintenance chemotherapy.
Ten consecutive children treated on the MRC ALL97 protocol were studied. Six were randomized to TG and four to MP. Leucocyte and erythrocyte thiopurine nucleotide metabolites were measured after the children had been titrated to the standard thiopurine protocol dose, or higher.
Children taking TG accumulated significantly higher erythrocyte TGN concentrations than those taking MP (median difference 1171 pmol/8 x 10(8) erythrocytes, 95% CI 766 to 2169, P<0.02), but there was no significant difference in the concentration range of leucocyte TGNs generated from TG or MP. In those children taking TG, median TGN concentrations were 5142 pmol/8 x 10(8) leucocytes and 1472 pmol/8 x 10(8) erythrocytes (3.5-fold difference, median difference 3390 pmol/8 x 10(8) cells, 95% CI 1559 to 7695, P=0.005), compared to 5422 pmol/8 x 10(8) leucocytes and 261 pmol/8 x 10(8) erythrocytes (20-fold difference, median difference 5054 pmol/8 x 10(8) cells, 95% CI 2281 to 6328, P=0.03) in those taking MP.
Despite the accumulation of significantly higher erythrocyte TGN concentrations for TG compared with MP, the accumulation of leucocyte TGNs in children taking TG was similar to the range of leucocyte TGNs in children taking MP. Therefore, when correlating intracellular TGNs to clinical effect, the range of erythrocyte TGN metabolites will be higher for those children taking TG than in those taking MP.
本研究旨在比较接受巯嘌呤(MP)或硫鸟嘌呤(TG)作为长期缓解维持化疗一部分的淋巴细胞白血病患儿的白细胞和红细胞硫鸟嘌呤核苷酸(TGN)细胞毒性代谢物浓度。
对按照MRC ALL97方案治疗的连续10名患儿进行研究。6名随机分配至TG组,4名至MP组。在患儿滴定至标准硫嘌呤方案剂量或更高剂量后,测量白细胞和红细胞硫嘌呤核苷酸代谢物。
服用TG的患儿红细胞TGN浓度显著高于服用MP的患儿(中位数差异为1171 pmol/8×10⁸红细胞,95%可信区间为766至2169,P<0.02),但由TG或MP产生的白细胞TGN浓度范围无显著差异。在服用TG的患儿中,TGN中位数浓度为5142 pmol/8×10⁸白细胞和1472 pmol/8×10⁸红细胞(差异3.5倍,中位数差异为3390 pmol/8×10⁸细胞,95%可信区间为1559至7695,P = 0.005),相比之下,服用MP的患儿为5422 pmol/8×10⁸白细胞和261 pmol/8×10⁸红细胞(差异20倍,中位数差异为5054 pmol/8×10⁸细胞,95%可信区间为2281至6328,P = 0.03)。
尽管与MP相比,TG的红细胞TGN浓度显著更高,但服用TG的患儿白细胞TGN的积累与服用MP的患儿白细胞TGN的范围相似。因此,当将细胞内TGN与临床效果相关联时,服用TG的患儿红细胞TGN代谢物的范围将高于服用MP的患儿。