Comparison of standardized prophylactic high-dose and intrathecal methotrexate for DLBCL with a high risk of CNS relapse

Int J Hematol. 2024 Feb;119(2):164-172. doi: 10.1007/s12185-023-03700-0. Epub 2024 Jan 17.


The efficacy of high-dose methotrexate (HD-MTX) for central nervous system (CNS) relapse prophylaxis in patients with high-risk diffuse large B-cell lymphoma (DLBCL) is controversial. We compared the prophylactic effects of HD-MTX and intrathecal methotrexate (IT-MTX) on CNS relapse in high-risk DLBCL, in a multicenter retrospective study. A total of 132 patients with DLBCL at high risk of CNS relapse who received frontline chemotherapy and IT-MTX from 2003 to 2013 (n = 34) or HD-MTX from 2014 to 2020 (n = 98) were included. After a median follow-up of 52 months (range: 9-174), 11 patients had isolated CNS relapse: six (6.1%) in the HD-MTX group and five (14.7%) in the IT-MTX group. The median time until CNS relapse was 38 months (range: 11-122), and the cumulative incidence of CNS relapse at 3 years was 3.9% in the HD-MTX group and 6.1% in the IT-MTX group (P = 0.93). Similar results were obtained after adjusting for background factors using propensity score-matched analysis (4.5% HD-MTX vs. 7.6% IT-MTX, P = 0.84). The CNS relapse rate in HD-MTX-treated patients was equivalent to that in IT-MTX patients, demonstrating that HD-MTX was not superior to IT-MTX in preventing CNS relapse.

Keywords: Central nervous system prophylaxis; Central nervous system relapse; Diffuse large B-cell lymphoma; High-dose methotrexate; Intrathecal methotrexate.

Publication types

  • Multicenter Study

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Central Nervous System Neoplasms* / drug therapy
  • Central Nervous System Neoplasms* / prevention & control
  • Chronic Disease
  • Humans
  • Lymphoma, Large B-Cell, Diffuse* / drug therapy
  • Lymphoma, Large B-Cell, Diffuse* / pathology
  • Methotrexate
  • Neoplasm Recurrence, Local / drug therapy
  • Neoplasm Recurrence, Local / prevention & control
  • Retrospective Studies


  • Methotrexate