Rare-13hyperacute Adverse Events of High-Dose Methotrexate Monotherapy in Primary Cns Lymphoma Patients

OBJECTIVES: High-dose methotrexate chemotherapy (HD-MTX) is the mainstay in treatment of primary CNS lymphoma (PCNSL) and has been known to have acute or late toxicity on skin, gastrointestinal mucosa, liver, kidneys, and bone marrow. However, hyperacute adverse events (HADE), which occurred within one hour of HD-MTX administration, are rarely known in PCNSL patients. We report our HADE experiences with 9 consecutive cases. METHODS: Of 51 PCNSL patients, 38 immunocompetent adult PCNSL patients treated with HD-MTX at Seoul St. Mary's Hospital, The Catholic University of Korea between 2004 and 2015 were investigated. Our HD-MTX monotherapy regimen consists of induction period (8 g/m2 on day 1, 10, and 20 for 3 cycles) and maintenance period (3.5 g/m2, every 4 weeks for 3 cycles and then every 3 months for 3 cycles). Medical records were reviewed for each of the HADE events, retrospectively. RESULTS: Of 38 patients who received HD-MTX of 247 cumulative cycles, 9 patients (23.7%; 4 men and 5 women) presented 13 HADE. Median age of the patients was 58 years (range 47 to 64 years) at the time of the event. HADE developed during the maintenance period in 5 patients, at the early induction period in 1 patient and at the rechallenging period for recurrence in 3 patients. HADE symptoms were variable; most commonly skin rashes in 12 events (92.3%), abdominal pain in 2 events (15.4%), and most severely hypotension in 1 event (7.7%). HD-MTX monotherapy was discontinued in 4 patients, continued with corticosteroid premedication and symptomatic application of antihistamine with or without MTX dose modification in 5 patients, and completed in 2 patients. CONCLUSION: Although HD-MTX appears to be a relatively safe medication, greater awareness of possible HADE in HD-MTX chemotherapy is needed for its prevention, early diagnosis and management. Studies to clarify its mechanism should be warranted.