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Diagnosis requires specialized hematopathology laboratories, with immunophenotypic analysis essential for confirming B\u2010cell lineage and identifying variants.\n                    <jats:italic>MYC<\/jats:italic>\n                    and\n                    <jats:italic>BCL2<\/jats:italic>\n                    rearrangements indicate a poor prognosis. Staging and prognosis rely on positron emission tomography computed tomography (PET\u2010CT). The International Prognostic Index (IPI) aids risk stratification. PET\u2010CT is critical for assessing treatment response and guiding strategies. First\u2010line management for LBCL can be informed by interim PET to assess chemosensitivity, with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R\u2010CHOP) or polatuzumab vedotin rituximab, cyclophosphamide, doxorubicin, and prednisone (Pola\u2010R\u2010CHP) for advanced stages depending on IPI scores. Primary mediastinal B\u2010cell lymphoma (PMBCL) management favors R\u2010CHOP given every 14 days (R\u2010CHOP14) or dose\u2010adjusted etoposide, doxorubicin, vincristine, cyclophosphamide, prednisone, and rituximab (DA\u2010EPOCH\u2010R) without radiotherapy in complete responders. Elderly patients, unfit or not (\u226580 years or &lt;80 with poor fitness), need geriatric assessment to guide therapy, often R\u2010miniCHOP or non\u2010anthracycline regimens. Frail patients should have adapted treatments. Prephase corticosteroids improve performance status, and supportive treatment should be optimized. The value of central nervous system (CNS) prophylaxis remains uncertain. CNS\u2010IPI scores and specific anatomical sites help identify high\u2010risk patients; magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) analysis are recommended. Approximately 30%\u201340% of patients with LBCL experience relapsed or refractory disease after 1L treatment. Treatment strategies vary based on the timing of relapse (&lt;1 year or \u22651 year). For those refractory or relapsing within &lt;1 year and fit for therapy, chimeric antigen receptor T (CART) are the gold standard in 2L. CART in CART\u2010na\u00efve patients and bispecific antibodies appear to be the best approach in 3L. Follow\u2010up includes clinical examination for 2 years and management for long\u2010term side effects, such as cardiotoxicity, osteoporosis, immune dysfunction, neurocognitive impairment, endocrine dysfunction, fatigue, neuropathy, and mental distress.\n                  <\/jats:p>","DOI":"10.1002\/hem3.70207","type":"journal-article","created":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T14:37:41Z","timestamp":1758638261000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["Large B\u2010cell lymphoma (LBCL): EHA Clinical Practice Guidelines for diagnosis, treatment, and follow\u2010up"],"prefix":"10.1002","volume":"9","author":[{"given":"Catherine","family":"Thieblemont","sequence":"first","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9 Paris France"},{"name":"Hemato\u2010oncologie Assistance Publique \u2013 H\u00f4pitaux de Paris, H\u00f4pital Saint Louis Paris 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