Limited efficacy of high-dose methotrexate in patients with neurolymphomatosis

Neurolymphomatosis (NL) is a rare manifestation of non-Hodgkin lymphoma, in which malignant cells infiltrate the peripheral nerves. Most patients are treated with high-dose methotrexate (HD-MTX)-based systemic chemotherapy regimens similar to patients with central nervous system lymphoma. However, because NL is rare, the efficacy of HD-MTX is largely unknown. We reviewed medical records of patients diagnosed with NL over the past 10 years and identified 18 patients. The underlying hematological malignancy was diffuse large B-cell lymphoma (DLBCL) in 10 patients (55.6%), intravascular large B-cell lymphoma in six (33.3%), and other types in two patients. Ten patients were treated with HD-MTX-based systemic chemotherapy; the response rates with and without HD-MTX-based chemotherapy were 100% (n = 10) and 85.7% (n = 6), respectively (P = 0.41). The median progression-free and overall survival rates of patients with versus without HD-MTX treatment were 6.4 vs. 8.5 months (P = 0.97) and 13.5 vs. 8.5 months (P = 0.63), respectively. Despite the initial favorable responses, rapid disease recurrence was observed in most patients administered HD-MTX-based chemotherapy. Our observations suggest that HD-MTX-based chemotherapy may have insufficient efficacy against NL, and that other therapeutic approaches are required to improve the outcomes of patients with this rare disease.