Systemic HD-MTX for CNS prophylaxis in high-risk DLBCL patients: a prospectively collected, single-center cohort analysis

We evaluated the efficacy of systemic high-dose methotrexate (HD-MTX) for CNS prophylaxis in a prospectively recruited cohort of DLBCL patients at high risk of CNS relapse. High-risk CNS relapse was defined as the involvement of ≥ 2 extranodal sites with elevated lactate dehydrogenase (LDH); CNS international prognostic index (CNS-IPI) ≥ 4; or involvement of high-risk extranodal sites, including bone marrow, breasts, testes, and paranasal sinuses. Overall, 130 patients who received at least two cycles of standard chemoimmunotherapy were evaluated; of these, 64 patients received additional systemic HD-MTX, either on day 15 of alternating cycles or 2–5 weeks after completion of primary therapy. Patients receiving HD-MTX showed a generally higher risk of CNS relapse than the other 66 patients not receiving prophylaxis. The estimated 2-year cumulative CNS relapse, progression-free survival and overall survival rates were 8.1%, 66.3%, and 77.5%, respectively, in patients who received systemic HD-MTX and 6.9%, 67.4%, and 71.4%, respectively, in patients without prophylaxis, with no significant between-group differences. Although this study does not show that systemic HD-MTX is definitively effective, these results may be of help to other researchers investigating the utility of HD-MTX prophylaxis in mitigating negative risk factors.