Experience with ambulatory high-dose methotrexate administration as CNS prophylaxis in patients with non-Hodgkin lymphoma.

BACKGROUND

We describe the feasibility and safety of an oral administration schedule of hydration, alkalinization and leucovorin rescue with an ambulatory high-dose methotrexate regimen.

METHODS

Single-centre prospective observational study conducted within a tertiary hospital where all patients have received systemic high-dose methotrexate (3.5 g/m). Patients were instructed to keep an adequate ambulatory oral hydration and alkalinization to monitor urine pH and to adjust bicarbonate according to our institution's treatment protocol. High-dose methotrexate was infused over 4 h. Urine pH was checked before high-dose methotrexate administration, and for any value less than 7 a sodium bicarbonate bolus was given. Leucovorin at a standard dose was begun 24 h after high-dose methotrexate. methotrexate serum concentrations were monitored daily from 24 h after administration until clearance (level ≤ 0.1 µmol/L).

RESULTS

From January 2016 to June 2018, 49 ambulatory high-dose methotrexate courses were given to 18 patients. No dose reduction was required afterwards. All patients completed succesfully the planned three doses in an outpatient basis, except four patients, one of them due to pneumonitis. Previous to methotrexate infusion, urinary pH > 7 was achieved in 35 (79.5%) cycles. Methotrexate clearance was achieved by 72 h in 35 courses (71.4%), and by 96 h in 100%. Neutropenia/trombocytopenia grades III/IV were observed in four cycles (8.16%) and two (4.08%) cycles, respectively. Around 20.40% were associated with stomatitis, 14.20% vomiting, 10.20% asthenia, 8.16% diarrhea and 6.12% with renal toxicity.

CONCLUSIONS

Ambulatory administration of high-dose methotrexate as CNS prophylaxis is safe and feasible following the described approach, allowing us to optimize healthcare resources.