Changes in Plasma Methionine and Total Homocysteine Levels in Patients Receiving Methotrexate Infusions1

Methotrexate reduces intracellular pools of 5-methyltetrahydrofolate and could result in reduced conversion of homocysteine to methionine by methionine synthetase. This study was designed to investigate the effects of moderate dose to very high dose methotrexate on methionine and total homocysteine as reflections of methotrexate induced intracellular events. Methionine and total homocysteine were measured prior to, during, and following twenty-six 24-h i.v. infusions of 33.6 g/m2 methotrexate (very high dose methotrexate) in 16 children with acute lymphocytic leukemia and seven 4-h i.v. infusions of 8 g/m2 methotrexate (high dose metho trexate) in 5 children with osteogenic sarcoma. Amino acids were meas ured by gas chromatography/mass spectrophotometry. Mean methionine levels decreased by 70.0 ±3.1% (SE) with very high dose methotrexate and 72.6 ±5.9% with high dose methotrexate at 24 and 4.5 h, respec tively, after beginning methotrexate infusions. Mean total homocysteine levels increased by 61.7 ±3.1% with very high dose methotrexate and 55.6 ±17.5% with high dose methotrexate at 36 and 24 h, respectively, after beginning methotrexate infusions. No consistent or significant changes were noted in levels of total cysteine, leucine, isoleucine, or valine. Similar changes did not occur in patients receiving prednisone, vincristine, daunomycin, and intrathecal methotrexate as therapy for acute lymphocytic leukemia. These changes in homocysteine and methi onine may reflect biological effects of methotrexate that may predict cytotoxicity of methotrexate.