# Treatment-related leukoencephalopathy in adults with central nervous system lymphoma: a retrospective analysis of 126 patients

## TL;DR

This study examines neurological complications in patients with central nervous system lymphoma, finding that intrathecal methotrexate significantly increases the risk of treatment-related leukoencephalopathy.

## Contribution

The study identifies intrathecal methotrexate as a significant risk factor for treatment-related leukoencephalopathy in CNS lymphoma patients.

## Key findings

- Treatment-related leukoencephalopathy occurred in 29.2% of patients two years after chemotherapy.
- Intrathecal methotrexate was found to be the only significant risk factor for tLE development.
- The number of intrathecal methotrexate doses correlated with increased tLE incidence and severity.

## Abstract

Neurotoxicity associated with high-dose chemotherapy and whole brain radiotherapy (WBRT) is one of major complications for patients with central nervous system lymphoma (CNSL). Here we determined the incidence and risk factors of treatment-related leukoencephalopathy (tLE) in a clinical setting. We retrospectively reviewed clinical and radiological findings of 126 patients with  (CNSL) treated with high-dose methotrexate with or without intrathecal methotrexate administration (IT MTX) and response-adapted WBRT. During the whole observation period with a median of 38.7 months, tLE was found in 33 patients, most of them asymptomatic, with the median time to development 3.0 months, and the cumulative incidence reaching 29.2% (95% confidence interval, 20.6–38.2%) two years post chemotherapy. By multivariable analysis, IT MTX was identified as the only one significant risk factor (hazard ratio, 4.50; P < 0.001), and the number of IT MTX was associated with the increased incidence and severity of tLE. These findings highlight the frequent neurological complications associated with CNS-directed therapy and confirm the neurotoxicity of IT MTX.

The online version contains supplementary material available at 10.1007/s00277-024-05989-1.