White matter changes in primary central nervous system lymphoma patients treated with high-dose methotrexate with or without rituximab

Fayez Estephan, Xiaobu Ye, Omar Dzaye, Nina Wagner-Johnston, Lode Swinnen, Douglas E. Gladstone, Rich Ambinder, David Olayinka Kamson, Sebastian Lambrecht, Stuart A. Grossman, Doris D.M. Lin, Matthias Holdhoff

Research output: Contribution to journalArticlepeer-review


Purpose: White matter changes (WMCs) can develop following systemic chemotherapy in patients with primary central nervous system lymphomas (PCNSLs), but the frequency and extent of these changes is not well characterized. This single center retrospective semi-quantitative study was performed to determine the rate, timing and grade of WMC on MRI in adult patients with newly-diagnosed radiotherapy-naïve PCNSL undergoing treatment with high-dose methotrexate (HD-MTX) with or without the addition of rituximab (-R). Methods: Serial MRI scans of consecutive adult PCNSL patients treated with HD-MTX ± R were assessed for WMC comparing the pre-treatment to post-treatment scans utilizing a 0-to-8-point severity scoring system. Results: Forty-seven PCNSL patients treated with either HD-MTX-R (n = 34; median age 66, 50% male) or HD-MTX (n = 13; median age 53, 54% male) were included in the analysis. WMC were detected in 62% (95% CI 46–76%) overall, in 68% of the HD-MTX-R, and in 46% of the HD-MTX group. Among patients with WMC (n = 29), WMC were first detected at an average of 2.8 months from beginning of therapy in the HD-MTX-R versus at 10.7 months in the HD-MTX group. Average WMC non-zero scores when first detected following the start of treatment were 2.5 (± 1.1) in HD-MTX-R and 1.5 (± 0.6) in HD-MTX. Conclusions: Development of WMC in PCNSL patients treated with MTX and MTX-R is common. WMC changes appear to be more frequent, occur earlier and are more extensive in patients treated with HD-MTX-R compared to HD-MTX. Prospective studies are required to determine whether WMC correlate with survival or neurocognitive outcomes.

Original languageEnglish (US)
Pages (from-to)461-466
Number of pages6
JournalJournal of neuro-oncology
Issue number3
StatePublished - Dec 1 2019


  • High-dose methotrexate
  • Leukoencephalopathy
  • Primary central nervous system lymphoma
  • Rituximab
  • White matter changes

ASJC Scopus subject areas

  • Oncology
  • Neurology
  • Clinical Neurology
  • Cancer Research

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