Leucocyte versus erythrocyte thioguanine nucleotide concentrations in children taking thiopurines for acute lymphoblastic leukaemia

Heading

Abstract

Purpose. 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.

Methods. 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.

Results. Children taking TG accumulated significantly higher erythrocyte TGN concentrations than those taking MP (median difference 1171 pmol/8×10⁸ 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/8×10⁸ leucocytes and 1472 pmol/8×10⁸ erythrocytes (3.5-fold difference, median difference 3390 pmol/8×10⁸ cells, 95% CI 1559 to 7695, P=0.005), compared to 5422 pmol/8×10⁸ leucocytes and 261 pmol/8×10⁸ erythrocytes (20-fold difference, median difference 5054 pmol/8×10⁸ cells, 95% CI 2281 to 6328, P=0.03) in those taking MP.

Conclusions. 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.