¹Department of Pharmaceutical Sciences, St Jude Children's Research Hospital, Memphis, TN USA

²Department of Biostatistics, St Jude Children's Research Hospital, Memphis, TN, USA

³Department of Hematology-Oncology, St Jude Children's Research Hospital, Memphis, TN, USA

⁴University of Tennessee, Memphis, TN, USA

Correspondence to: M V Relling, Department of Pharmaceutical Sciences, St Jude Children's Research Hospital, 332 North Lauderdale Memphis, 38105 TN, USA; Fax: 901-525-6869

Methotrexate is widely administered with mercaptopurine, a prodrug requiring activation into thioguanine nucleotides (TGN) to exert antileukemic effects. In vitro, methotrexate enhances TGN formation, but in vivo, such enhancement has yet to be demonstrated. We investigated whether TGN concentrations were related to methotrexate concentrations in children with acute lymphoblastic leukemia who received a weekly intravenous methotrexate (40 mg/m²) dose combined with daily mercaptopurine (75 mg/m²). A total of 141 erythrocyte TGN concentrations were measured with erythrocyte methotrexate polyglutamates (MTX-PG) concentrations in 87 patients. Average TGN concentrations ranged from 137 to 958 pmol/8 ´ 10⁸ cells (median 389), average total MTX-PG concentrations (MTX- PG_1-7) from 0.60 to 97.7 pmol/10⁹cells (median 29), and average long chain polyglutamate concentrations (MTX-PG_5-7) from 0 to 8.35 pmol/10⁹ cells (median 2.43). Higher TGN concentrations correlated with higher MTX-PG_5-7 concentrations (P = 0.002). These data support the practice of administering methotrexate with mercaptopurine during continuation therapy of acute lymphoblastic leukemia.

Leukemia (2002) 16, 209-212. DOI: 10.1038/sj/leu/2402373

mercaptopurine; methotrexate; leukemia; thioguanine nucleotides