Lennard L, Lilleyman J S, Maddocks J L
Br J Cancer. 1986 Jan;53(1):115-9. doi: 10.1038/bjc.1986.16.
The effect of folic acid supplements on 6-mercaptopurine remission maintenance therapy in lymphoblastic leukaemia (ALL) was investigated in a retrospective longitudinal study of 10 children. Red cell concentrations of 6-thioguanine nucleotide, a cytotoxic metabolite of 6-mercaptopurine, were measured and the peripheral neutrophil count was used as an index of myelosuppression. During the control period of the study there were significant correlations between 6-mercaptopurine dose and 6-thioguanine nucleotide concentration (rs = 0.59, P less than 0.0005) and between 6-thioguanine nucleotide concentration and the peripheral neutrophil count at 14 days (rs = 0.58, P less than 0.0005). These relationships were absent when the same children were subsequently taking folate supplements. Also when taking folate supplements the children tolerated significantly more 6-mercaptopurine (P less than 0.005) for a significantly longer time (P less than 0.005) before neutropenia developed. There was no significant difference in red cell 6-thioguanine nucleotide concentration in the absence and presence of folate supplements. These findings suggest that folate supplements may interfere with remission maintenance therapy in ALL.
在一项对10名儿童的回顾性纵向研究中，调查了叶酸补充剂对淋巴细胞白血病（ALL）中6-巯基嘌呤缓解维持治疗的影响。测量了6-巯基嘌呤的细胞毒性代谢产物6-硫鸟嘌呤核苷酸的红细胞浓度，并将外周血中性粒细胞计数用作骨髓抑制的指标。在研究的对照期，6-巯基嘌呤剂量与6-硫鸟嘌呤核苷酸浓度之间存在显著相关性（rs = 0.59，P小于0.0005），以及在14天时6-硫鸟嘌呤核苷酸浓度与外周血中性粒细胞计数之间存在显著相关性（rs = 0.58，P小于0.0005）。当这些儿童随后服用叶酸补充剂时，这些关系消失了。同样，在服用叶酸补充剂时，儿童在中性粒细胞减少症出现之前能够耐受显著更多的6-巯基嘌呤（P小于0.005），且耐受时间显著更长（P小于0.005）。在有无叶酸补充剂的情况下，红细胞6-硫鸟嘌呤核苷酸浓度没有显著差异。这些发现表明，叶酸补充剂可能会干扰ALL的缓解维持治疗。
