{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T19:28:46Z","timestamp":1793734126884,"version":"4.6.1"},"reference-count":64,"publisher":"American Society of Hematology","issue":"9","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Primary central nervous system lymphoma (PCNSL) is a rare extranodal lymphomatous malignancy that affects the brain, spinal cord, leptomeninges, or vitreoretinal space, without evidence of systemic involvement. The diagnosis of PCNSL requires a high level of suspicion because clinical presentation varies depending upon involved structures. Initiation of treatment is time sensitive for optimal neurologic recovery and disease control. In general, the prognosis of PCNSL has improved significantly over the past few decades, largely as a result of the introduction and widespread use of high-dose methotrexate (MTX) chemotherapy, which is considered the backbone of first-line polychemotherapy treatment. Upon completion of MTX-based treatment, a consolidation strategy is often required to prolong duration of response. Consolidation can consist of radiation, maintenance therapy, nonmyeloablative chemotherapy, or myeloablative treatment followed by autologous stem cell transplant. Unfortunately, even with consolidation, relapse is common, and 5-year survival rates stand at only 30% to 40%. Novel insights into the pathophysiology of PCNSL have identified key mechanisms in tumor pathogenesis, including activation of the B-cell receptor pathway, immune evasion, and a suppressed tumor immune microenvironment. These insights have led to the identification of novel small molecules targeting these aberrant pathways. The Bruton tyrosine kinase inhibitor ibrutinib and immunomodulatory drugs (lenalidomide or pomalidomide) have shown promising clinical response rates for relapsed\/refractory PCNSL and are increasingly used for the treatment of recurrent disease. This review provides a discussion of the clinical presentation of PCNSL, the approach to work-up and staging, and an overview of recent advancements in the understanding of the pathophysiology and current treatment strategies for immunocompetent patients.<\/jats:p>","DOI":"10.1182\/blood.2020008377","type":"journal-article","created":{"date-parts":[[2021,10,26]],"date-time":"2021-10-26T15:04:33Z","timestamp":1635260673000},"page":"971-979","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":232,"title":["Primary central nervous system lymphoma"],"prefix":"10.1182","volume":"140","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4664-670X","authenticated-orcid":false,"given":"Lauren R.","family":"Schaff","sequence":"first","affiliation":[{"name":"1Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, NY; and"},{"name":"2Department of Neurology, Weill Cornell Medical College, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7485-0441","authenticated-orcid":false,"given":"Christian","family":"Grommes","sequence":"additional","affiliation":[{"name":"1Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, NY; and"},{"name":"2Department of Neurology, Weill Cornell Medical College, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","reference":[{"issue":"21","key":"2022090115232508900_B1","doi-asserted-by":"crossref","first-page":"2410","DOI":"10.1200\/JCO.2017.72.7602","article-title":"Primary CNS lymphoma","volume":"35","author":"Grommes","year":"2017","journal-title":"J Clin Oncol."},{"issue":"6","key":"2022090115232508900_B2","first-page":"1476","article-title":"Central nervous system lymphomas","volume":"26","author":"Grommes","year":"2020","journal-title":"Continuum (Minneap Minn)."},{"issue":"5","key":"2022090115232508900_B3","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1093\/neuonc\/nox187","article-title":"The elderly left behind-changes in survival trends of primary central nervous system lymphoma over the past 4 decades","volume":"20","author":"Mendez","year":"2018","journal-title":"Neuro-oncol."},{"issue":"3","key":"2022090115232508900_B4","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1111\/bjh.14073","article-title":"Trends in primary central nervous system lymphoma incidence and survival in the U.S","volume":"174","author":"Shiels","year":"2016","journal-title":"Br J Haematol."},{"issue":"9","key":"2022090115232508900_B5","doi-asserted-by":"crossref","first-page":"1414","DOI":"10.1038\/bjc.2011.357","article-title":"Age, gender, and racial differences in incidence and survival in primary CNS lymphoma","volume":"105","author":"Villano","year":"2011","journal-title":"Br J Cancer."},{"issue":"2","key":"2022090115232508900_B6","doi-asserted-by":"crossref","first-page":"261","DOI":"10.3171\/jns.2000.92.2.0261","article-title":"Primary intracerebral malignant lymphoma: report of 248 cases","volume":"92","author":"Bataille","year":"2000","journal-title":"J Neurosurg."},{"issue":"11","key":"2022090115232508900_B7","doi-asserted-by":"crossref","first-page":"1851","DOI":"10.1093\/annonc\/mdm340","article-title":"Primary intraocular lymphoma: an International Primary Central Nervous System Lymphoma Collaborative Group Report","volume":"18","author":"Grimm","year":"2007","journal-title":"Ann Oncol."},{"key":"2022090115232508900_B8","doi-asserted-by":"crossref","first-page":"15","DOI":"10.21037\/aol-20-52","article-title":"Positron emission tomography and magnetic resonance imaging in primary central nervous system lymphoma-a narrative review","volume":"5","author":"Krebs","year":"2021","journal-title":"Ann Lymphoma."},{"issue":"4","key":"2022090115232508900_B9","doi-asserted-by":"crossref","first-page":"E192","DOI":"10.1093\/neuros\/nyy328","article-title":"In reply: craniotomy and survival for primary central nervous system lymphoma","volume":"83","author":"Rae","year":"2018","journal-title":"Neurosurgery."},{"issue":"5","key":"2022090115232508900_B10","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1093\/ajcp\/110.5.607","article-title":"Primary central nervous system lymphomas in 72 immunocompetent patients: pathologic findings and clinical correlations. 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