{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T05:11:52Z","timestamp":1789708312325,"version":"4.0.1"},"reference-count":120,"publisher":"Harborside Press, LLC","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,11]]},"abstract":"<jats:p>Primary central nervous system lymphomas (PCNSLs) are rare cancers of the central nervous system (CNS) and are predominantly diffuse large B-cell lymphomas of the activated B-cell (ABC) subtype. They typically present in the sixth and seventh decade of life, with the highest incidence among patients aged &gt;75 years. Although many different regimens have demonstrated efficacy in newly diagnosed and relapsed or refractory PCNSL, there have been few randomized prospective trials, and most recommendations and treatment decisions are based on single-arm phase II trials or even retrospective studies. High-dose methotrexate (HD-MTX; 3\u20138 g\/m<jats:sup>2<\/jats:sup>) is the backbone of preferred standard induction regimens. Various effective regimens with different toxicity profiles can be considered that combine other chemotherapies and\/or rituximab with HD-MTX, but there is currently no consensus for a single preferred regimen. There is controversy about the role of various consolidation therapies for patients who respond to HD-MTX\u2013based induction therapy. For patients with relapsed or refractory PCNSL who previously experienced response to HD-MTX, repeat treatment with HD-MTX\u2013based therapy can be considered depending on the timing of recurrence. Other more novel and less toxic regimens have been developed that show efficacy in recurrent disease, including ibrutinib, or lenalidomide \u00b1 rituximab. There is uniform agreement to delay or avoid whole-brain radiation therapy due to concerns for significant neurotoxicity if a reasonable systemic treatment option exists. This article aims to provide a clinically practical approach to PCNSL, including special considerations for older patients and those with impaired renal function. The benefits and risks of HD-MTX or high-dose chemotherapy with autologous stem cell transplantation versus other, better tolerated strategies are also discussed. In all settings, the preferred treatment is always enrollment in a clinical trial if one is available.<\/jats:p>","DOI":"10.6004\/jnccn.2020.7667","type":"journal-article","created":{"date-parts":[[2020,11,5]],"date-time":"2020-11-05T20:24:08Z","timestamp":1604607848000},"page":"1571-1578","source":"Crossref","is-referenced-by-count":58,"title":["Challenges in the Treatment of Newly Diagnosed and Recurrent Primary Central Nervous System Lymphoma"],"prefix":"10.6004","volume":"18","author":[{"given":"Matthias","family":"Holdhoff","sequence":"first","affiliation":[{"name":"1The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maciej M.","family":"Mrugala","sequence":"additional","affiliation":[{"name":"2Department of Neurology, Mayo Clinic, Phoenix, Arizona;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Grommes","sequence":"additional","affiliation":[{"name":"3Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, New York; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas J.","family":"Kaley","sequence":"additional","affiliation":[{"name":"3Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, New York; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lode J.","family":"Swinnen","sequence":"additional","affiliation":[{"name":"1The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Perez-Heydrich","sequence":"additional","affiliation":[{"name":"1The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lakshmi","family":"Nayak","sequence":"additional","affiliation":[{"name":"4Center for CNS Lymphoma, Dana-Farber Cancer Institute, Boston, Massachusetts."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4047","reference":[{"key":"ref1141","doi-asserted-by":"crossref","first-page":"3971","DOI":"10.1200\/JCO.2013.50.4910","article-title":"Rituximab, methotrexate, procarbazine, and vincristine followed by consolidation reduced-dose whole-brain radiotherapy and cytarabine in newly diagnosed primary CNS lymphoma: final results and long-term outcome","volume":"31","author":"Morris","year":"2013","journal-title":"J Clin Oncol"},{"key":"ref871","doi-asserted-by":"crossref","first-page":"1403","DOI":"10.1182\/blood-2014-10-604561","article-title":"R-MPV followed by high-dose chemotherapy with TBC and autologous stem-cell transplant for newly diagnosed primary CNS 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