{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T03:30:36Z","timestamp":1790566236294,"version":"4.1.0"},"reference-count":116,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2025,9,8]],"date-time":"2025-09-08T00:00:00Z","timestamp":1757289600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Richter transformation (RT) affects 2\u201310% of chronic lymphocytic leukemia (CLL) patients, evolving into an aggressive lymphoma\u2014most often diffuse large B-cell lymphoma\u2014with poor prognosis, especially when clonally related to CLL. Key risk factors include unmutated IGHV, TP53 and NOTCH1 mutations, stereotyped B-cell receptors, and complex cytogenetics. This review summarizes RT biology, clinical predictors, and treatment outcomes. Traditional chemoimmunotherapy (e.g., R-CHOP) yields complete response rates around 20\u201330% and median overall survival of 6\u201312 months; intensified regimens (R-EPOCH, hyper-CVAD) offer only modest gains. Allogeneic hematopoietic stem cell transplantation is potentially curative but limited to fit patients due to high treatment-related mortality. Emerging therapies now include Bruton\u2019s tyrosine kinase and BCL-2 inhibitors, which achieve partial responses but short progression-free survival. CD19-directed chimeric antigen receptor T-cell therapies produce overall response rates of 60\u201365%, though relapses remain frequent. Bispecific antibodies (e.g., CD3\u00d7CD20 agents epcoritamab and mosunetuzumab) show promising activity and tolerable toxicity in relapsed\/refractory RT. Ongoing trials are exploring combinations with checkpoint inhibitors, triplet regimens, and novel targets such as ROR1, CD47, and CDK9. Continued research into optimized induction, consolidation, and innovative immunotherapies is essential to improve outcomes in this biologically distinct, high-risk CLL-related lymphoma.<\/jats:p>","DOI":"10.3390\/ijms26178747","type":"journal-article","created":{"date-parts":[[2025,9,10]],"date-time":"2025-09-10T10:27:12Z","timestamp":1757500032000},"page":"8747","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Richter Transformation in Chronic Lymphocytic Leukemia: Current Treatment Challenges and Evolving Therapies"],"prefix":"10.3390","volume":"26","author":[{"given":"Zi-Chi","family":"Lin","sequence":"first","affiliation":[{"name":"Division of Hematology-Oncology, Department of Internal Medicine, Linkou Chang Gung Memorial Hospital, Taoyuan 333423, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1482-8557","authenticated-orcid":false,"given":"Ming-Jen","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Kidney Research Center, Linkou Chang Gung Memorial Hospital, Taoyuan 333423, Taiwan"},{"name":"College of Medicine, Chang Gung University, Taoyuan 333423, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5407-1555","authenticated-orcid":false,"given":"Tang-Her","family":"Jaing","sequence":"additional","affiliation":[{"name":"College of Medicine, Chang Gung University, Taoyuan 333423, Taiwan"},{"name":"Division of Hematology\/Oncology, Department of Pediatrics, Chang Gung Memorial Hospital in Linkou, Taoyuan 333423, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9532-749X","authenticated-orcid":false,"given":"Tung-Liang","family":"Lin","sequence":"additional","affiliation":[{"name":"Division of Hematology-Oncology, Department of Internal Medicine, Linkou Chang Gung Memorial Hospital, Taoyuan 333423, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Shin","family":"Hung","sequence":"additional","affiliation":[{"name":"Division of Hematology-Oncology, Department of Internal Medicine, Linkou Chang Gung Memorial Hospital, Taoyuan 333423, Taiwan"},{"name":"College of Medicine, Chang Gung University, Taoyuan 333423, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8372-1166","authenticated-orcid":false,"given":"Yi-Jiun","family":"Su","sequence":"additional","affiliation":[{"name":"Division of Hematology-Oncology, Department of Internal Medicine, Linkou Chang Gung Memorial Hospital, Taoyuan 333423, Taiwan"},{"name":"College of Medicine, Chang Gung University, Taoyuan 333423, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4648","DOI":"10.1200\/JCO.2006.09.4508","article-title":"Assessment of chronic lymphocytic leukemia and small lymphocytic lymphoma by absolute lymphocyte counts in 2,126 patients: 20 years of experience at the University of Texas M.D. Anderson Cancer Center","volume":"25","author":"Tsimberidou","year":"2007","journal-title":"J. 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