High-Dose Methotrexate as CNS Prophylaxis in Ultra High-Risk Large B-Cell Lymphoma: An International Multicenter Analysis

作者：Matthew R. Wilson, Katharine L. Lewis, Amy A. Kirkwood, Kate Cwynarski, Chan Y. Cheah, Tarec C. El-Galaly, Diego Villa, Kerry J. Savage, Paola Ghione, Sabela Bobillo, Karin E. Smedby, Sara Harrysson, Marek Trněný, Magdalena Klánová, Robert Puckrin, Christopher P. Fox, Mark Bishton, Gita Thanarajasingam, Nicole Wong Doo, Greg Hapgood, Carole Soussain, Sylvain Choquet, Michael Dickinson, Dipti Talaulikar, Sanjay De Mel, Gavin Preston, Matthew J. Ahearne, Eliza A. Hawkes, Elisabeth Schorb, Aline Clavert, Matthew Ku, Anna Guidetti, Mayur Narkhede, Teresa Calimeri, Éric Durot, Jeffrey Smith, Loïc Renaud, Pam McKay, Toby A. Eyre · 发表于：Journal of Clinical Oncology · 年份：2026 · DOI：10.1200/jco-26-00947 · 被引用次数：1 · 研究领域：CNS Lymphoma Diagnosis and Treatment、Lymphoma Diagnosis and Treatment、Acute Lymphoblastic Leukemia research

PURPOSE In large B-cell lymphoma (LBCL), use of high-dose methotrexate (HD-MTX) to prevent CNS relapse (so-called CNS prophylaxis) remains controversial. International guidelines continue to recommend HD-MTX in patients deemed ultra high risk (UHR) because of a lack of robust data specific to these subgroups. This study was designed to examine the impact of HD-MTX specifically in UHR patients. METHODS Data from two previous retrospective analyses were combined to produce a cohort of UHR patients (≥1 of the following criteria: CNS international prognostic index score 5-6; testicular, renal/adrenal, or breast involvement; ≥3 extranodal sites), treated with or without HD-MTX. The primary outcome was CNS relapse rate (isolated or concurrent with systemic relapse) measured from diagnosis with additional landmark analysis of all responding patients with no progression event at 6 months. RESULTS Analyses were performed on 1,923 patients meeting UHR criteria. No significant difference in 3-year CNS relapse rate was observed between no HD-MTX (n = 1,051) versus HD-MTX patients (n = 872), including in multivariable analyses adjusting for baseline characteristics (3-year rate, 9.3% v 8.1%; adjusted hazard ratio [HR], 1.13 [95% CI, 0.82 to 1.57]). Analyses restricted to isolated CNS relapse also confirmed no difference (5.9% v 5.7%; adjusted HR, 1.03 [95% CI, 0.69 to 1.53]). In the landmark analysis (no HD-MTX n = 782, HD-MTX n = 773), no difference in 3-year CNS relapse was observed (6....