High-dose methotrexate therapy for primary central nervous system lymphoma: a practical approach amid limitations in toxicity monitoring – a case report
Abstract
Primary central nervous system lymphoma (PCNSL) is a rare subtype of non-Hodgkin lymphoma. High-dose methotrexate (HD-MTX)-based chemoimmunotherapy represents the standard treatment. Drug safety requires therapeutic drug monitoring (TDM) of serum MTX levels; however, in many resource-limited settings, such facilities are not available. We report a 57-year-old male with PCNSL diagnosed in July 2024 based on brain MRI and histopathology confirming diffuse large B-cell lymphoma. Baseline systemic evaluations were unremarkable. The patient presented with decreased consciousness and underwent wide excision tumor surgery. Pre-treatment performance status was ECOG 3 with GCS E3V4M5. Following informed consent, HD-MTX 3.5 g with rituximab 375 mg/m² was administered every three weeks for four cycles. Leucovorin rescue (100 mg every six hours for five days) and sodium bicarbonate were given as supportive measures. Routine hematology and renal function tests were monitored. During treatment, the patient experienced fatigue, mild anemia, grade 1–2 neutropenia, and mild creatinine elevation. Consciousness improved after the second cycle. Post-treatment MRI showed an 88% tumor reduction (partial response, RECIST criteria). One year post-diagnosis, the patient was alert, able to sit but not stand, with normal laboratory values. MRI revealed no residual tumor but demonstrated porencephaly. The patient was referred for physiotherapy. This case highlights that HD-MTX can be administered relatively safely in PCNSL patients even without TDM facilities, provided that modified folinic acid rescue protocols and close clinical–laboratory monitoring are implemented. Nonetheless, the establishment of TDM services remains crucial to optimize treatment safety and outcomes.
Primary central nervous system lymphoma (PCNSL) merupakan limfoma non-Hodgkin langka yang mengenai otak, medula spinalis, dan cairan serebrospinal. Terapi standar PCNSL adalah kemoimunoterapi berbasis metotreksat dosis tinggi (high-dose methotrexate/HD-MTX). Pemberian HD-MTX memerlukan pemantauan kadar obat (therapeutic drug monitoring/TDM), namun fasilitas ini sering tidak tersedia di daerah dengan keterbatasan sumber daya. Kami melaporkan seorang laki-laki berusia 57 tahun datang dengan keluhan nyeri kepala. Diagnosis PCNSL ditegakkan Juli 2024 melalui MRI otak dan histopatologi yang sesuai dengan diffuse large B-cell lymphoma (DLBCL). Pemeriksaan rontgen toraks serta ultrasonografi leher dan abdomen normal. Aspirasi sumsum tulang tidak dilakukan karena hasil hematologi normal. Pasien mengalami penurunan kesadaran sehingga dilakukan operasi eksisi tumor luas. Status performa sebelum kemoterapi adalah ECOG 3 dengan GCS E3V4M5. Pasien mendapat HD-MTX dosis 3,5 gram dan rituximab 375 mg/m² setiap 3 minggu selama 4 siklus. Leucovorin 100 mg diberikan tiap 6 jam selama 5 hari, dimulai 6 jam setelah infus HD-MTX, disertai natrium bikarbonat 25 mEq tiap 12 jam pada hari pertama. Pemantauan darah rutin, ureum, kreatinin, dan urinalisis dilakukan pada hari ke-1, 3, dan 5. Kesadaran pasien membaik setelah siklus kedua. Efek samping meliputi kelelahan, anemia ringan, neutropenia derajat 1–2, dan peningkatan kreatinin ringan. MRI otak pasca terapi menunjukkan respon parsial dengan penurunan ukuran tumor 88% (RECIST). Pasien menolak dirujuk untuk radioterapi. Setahun kemudian, pasien sadar penuh, mampu duduk tetapi belum berdiri. Pemeriksaan laboratorium normal, MRI otak menunjukkan tidak ada residu tumor namun terdapat porensefali. Pasien direncanakan fisioterapi dan evaluasi MRI 6–12 bulan kemudian. Kasus ini menunjukan bahwa HD-MTX dapat diberikan secara relatif aman pada PCNSL tanpa TDM melalui modifikasi protokol serta pemantauan ketat. Meski demikian, penyediaan fasilitas TDM tetap penting untuk menjamin keamanan sesuai standar terapi.
