Intermittent reduced-dose methotrexate enabled continuation of induction therapy despite severe delayed methotrexate elimination in primary central nervous system lymphoma: a case report

High-dose methotrexate (HD-MTX) is the backbone of induction therapy for primary central nervous system lymphoma (PCNSL) but may be limited by delayed elimination and renal toxicity. We report a clinically instructive case in which intermittent reduced-dose methotrexate allowed continuation of induction therapy after severe delayed elimination and acute kidney injury. A 59-year-old Japanese woman presented with headache and rapidly progressive impaired consciousness. Brain magnetic resonance imaging revealed a 5-cm enhancing mass in the right frontal lobe with significant perifocal edema. Emergent open biopsy confirmed PCNSL, diffuse large B-cell lymphoma, non-germinal center B-cell type, without systemic involvement. Induction chemotherapy with rituximab, methotrexate, procarbazine, and vincristine was initiated. After the first HD-MTX dose (3.5 g/m 2 ), methotrexate elimination was markedly delayed (72-h level 0.85 µmol/L; persistent elevation around day 7), accompanied by a > 60% reduction in estimated glomerular filtration rate from 79.2 to 29.4 mL/min/1.73 m 2 . Because of renal dysfunction, subsequent courses employed an intermittent reduced-dose methotrexate strategy (1.2 g/m 2 on selected cycles). With this approach, serum methotrexate concentrations remained within an acceptable therapeutic range without recurrent delayed elimination, and renal function gradually improved. Complete remission was achieved after induction, followed by consolidation with reduced-dose whole-brain radiotherapy and two courses of high-dose cytarabine. Complete remission has been maintained for 30 months after completion of the entire treatment sequence. When severe delayed methotrexate elimination and renal dysfunction occur early during HD-MTX-based induction for PCNSL, an intermittent reduced-dose strategy may allow continuation of methotrexate-based therapy and subsequent standard consolidation in selected settings. This case also highlights the practical importance of supportive care and individualized decision-making when glucarpidase is not readily available.