{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,11]],"date-time":"2026-01-11T16:44:21Z","timestamp":1768149861219,"version":"3.49.0"},"reference-count":82,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2023,3,20]],"date-time":"2023-03-20T00:00:00Z","timestamp":1679270400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1K08CA230319"],"award-info":[{"award-number":["1K08CA230319"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Edward P. Evans Foundation","award":["1K08CA230319"],"award-info":[{"award-number":["1K08CA230319"]}]},{"name":"Doris Duke Charitable Foundation","award":["1K08CA230319"],"award-info":[{"award-number":["1K08CA230319"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Richter Transformation (RT) refers to the development of an aggressive lymphoma in the setting of chronic lymphocytic leukemia (CLL). While many variants of RT are recognized, diffuse large B-cell lymphoma (RT-DLBCL) is the most common (80%), followed by Hodgkin\u2019s lymphoma (RT-HL, 19%). Diagnosis is based upon histologic evaluation of clinically suspicious lymph nodes. Positron emission tomography (PET) may be used to select the node of interest for biopsy. Although clonality testing is not a prerequisite of RT diagnosis, it has significant implications for survival. Clonally related DLBCL carries the worst prognosis with a median overall survival (OS) of less than one year in the era of combination chemotherapies with or without anti-CD20 antibodies. Prognosis has improved with the use of stem cell transplant and newer agents such as targeted therapy and newer forms of immunotherapy. Consideration of a clinical trial is encouraged. This review describes our current understanding of RT and focuses on treatment of RT-DLBCL, including clinical trials in progress and new therapies in development. We also report an illustrative example of a patient with clonally related DLBCL who survived two years after diagnosis without the use of combination chemotherapy.<\/jats:p>","DOI":"10.3390\/cancers15061857","type":"journal-article","created":{"date-parts":[[2023,3,20]],"date-time":"2023-03-20T03:30:31Z","timestamp":1679283031000},"page":"1857","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Treatment of Richter Transformation of Chronic Lymphocytic Leukemia in the Modern Era"],"prefix":"10.3390","volume":"15","author":[{"given":"Robert","family":"Briski","sequence":"first","affiliation":[{"name":"M.D. Anderson Cancer Center, Houston, TX 77030, USA"},{"name":"Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL 33136, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4407-6325","authenticated-orcid":false,"given":"Justin","family":"Taylor","sequence":"additional","affiliation":[{"name":"Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL 33136, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1111\/bjh.12458","article-title":"Diffuse large B-cell lymphoma (Richter syndrome) in patients with chronic lymphocytic leukaemia (CLL): A cohort study of newly diagnosed patients","volume":"162","author":"Parikh","year":"2013","journal-title":"Br. J. Haematol."},{"key":"ref_2","first-page":"448","article-title":"Clinical characteristics and outcome of young chronic lymphocytic leukemia patients: A single institution study of 204 cases","volume":"94","author":"Mauro","year":"1999","journal-title":"Blood J. Am. Soc. Hematol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2343","DOI":"10.1200\/JCO.2005.05.0187","article-title":"Clinical Outcomes and Prognostic Factors in Patients With Richter\u2019s Syndrome Treated With Chemotherapy or Chemoimmunotherapy With or Without Stem-Cell Transplantation","volume":"24","author":"Tsimberidou","year":"2006","journal-title":"J. Clin. Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3179","DOI":"10.1182\/blood.V112.11.3179.3179","article-title":"Richter transformation of chronic lymphocytic leukemia: Incidence, risk factors and outcome","volume":"112","author":"Alipour","year":"2008","journal-title":"Blood"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1749","DOI":"10.3109\/10428194.2012.664845","article-title":"Richter transformation in 16 of 149 Chinese patients with chronic lymphocytic leukemia","volume":"53","author":"Fan","year":"2012","journal-title":"Leuk. Lymphoma"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1111\/j.1365-2141.2008.07166.x","article-title":"Biological and clinical risk factors of chronic lymphocytic leukaemia transformation to Richter syndrome","volume":"142","author":"Rossi","year":"2008","journal-title":"Br. J. Haematol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"4415","DOI":"10.1158\/1078-0432.CCR-08-3266","article-title":"Stereotyped B-cell receptor is an independent risk factor of chronic lymphocytic leukemia transformation to Richter syndrome","volume":"15","author":"Rossi","year":"2009","journal-title":"Clin. Cancer Res."},{"key":"ref_8","first-page":"285","article-title":"Generalized Reticular Cell Sarcoma of Lymph Nodes Associated with Lymphatic Leukemia","volume":"4","author":"Richter","year":"1928","journal-title":"Am. J. Pathol."},{"key":"ref_9","first-page":"621","article-title":"Chronic lymphoid leukemia secondarily associated with a malignant reticulopathy: Richter\u2019s Syndrome","volume":"4","author":"Lortholary","year":"1964","journal-title":"Nouv. Rev. Fr. D\u2019hematologie"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2761","DOI":"10.1182\/blood-2018-01-791376","article-title":"Biology and treatment of Richter syndrome","volume":"131","author":"Rossi","year":"2018","journal-title":"Blood"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2272","DOI":"10.1182\/blood.2021010664","article-title":"Rapidly deteriorating B-CLL at presentation: Clonally related Burkitt leukemia as an atypical Richter transformation?","volume":"137","author":"Chatzidimitriou","year":"2021","journal-title":"Blood"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Imataki, O., and Uemura, M. (2018). B-chronic lymphocytic leukemia showed triple transformation, to diffuse large B cell, CD20-negative, and T-cell neoplasm during ofatumumab treatment: A case report. BMC Clin. Pathol., 18.","DOI":"10.1186\/s12907-018-0072-5"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e11619","DOI":"10.1097\/MD.0000000000011619","article-title":"A case report of extranodal NK\/T-cell lymphoma in patient with chronic lymphocytic leukemia","volume":"97","author":"Ge","year":"2018","journal-title":"Medicine"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1002\/cncr.20773","article-title":"Richter syndrome","volume":"103","author":"Tsimberidou","year":"2005","journal-title":"Cancer"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1093\/ajcp\/98.4.424","article-title":"Small B-cell lymphoid neoplasms with coexisting T-cell lymphomas","volume":"98","author":"Strickler","year":"1992","journal-title":"Am. J. Clin. Pathol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1093\/ajcp\/103.3.348","article-title":"B-cell chronic lymphocytic leukemia followed by high grade T-cell lymphoma. An unusual variant of Richter\u2019s syndrome","volume":"103","author":"Lee","year":"1995","journal-title":"Am. J. Clin. Pathol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1097\/PAS.0b013e31804bdaf8","article-title":"IgVH Mutational Status and Clonality Analysis of Richter\u2019s Transformation: Diffuse Large B-cell Lymphoma and Hodgkin Lymphoma in Association With B-cell Chronic Lymphocytic Leukemia (B-CLL) Represent 2 Different Pathways of Disease Evolution","volume":"31","author":"Mao","year":"2007","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1720","DOI":"10.1038\/s41375-022-01620-2","article-title":"The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Lymphoid Neoplasms","volume":"36","author":"Alaggio","year":"2022","journal-title":"Leukemia"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3391","DOI":"10.1182\/blood-2010-09-302174","article-title":"The genetics of Richter syndrome reveals disease heterogeneity and predicts survival after transformation","volume":"117","author":"Rossi","year":"2011","journal-title":"Blood"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1111\/j.1365-2141.2012.09155.x","article-title":"Different impact of NOTCH1 and SF3B1 mutations on the risk of chronic lymphocytic leukemia transformation to Richter syndrome","volume":"158","author":"Rossi","year":"2012","journal-title":"Br. J. Haematol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"868","DOI":"10.3324\/haematol.2021.278304","article-title":"The complex karyotype landscape in chronic lymphocytic leukemia allows the refinement of the risk of Richter syndrome transformation","volume":"107","author":"Visentin","year":"2022","journal-title":"Haematologica"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1111\/j.1365-2141.2007.06801.x","article-title":"Risk factors for development of a second lymphoid malignancy in patients with chronic lymphocytic leukaemia","volume":"139","author":"Slager","year":"2007","journal-title":"Br. J. Haematol."},{"key":"ref_23","first-page":"1267","article-title":"Detection of Richter\u2019s transformation of chronic lymphocytic leukemia by PET\/CT","volume":"47","author":"Bruzzi","year":"2006","journal-title":"J. Nucl. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2783","DOI":"10.1182\/blood-2013-11-536169","article-title":"Correlation between FDG\/PET, histology, characteristics, and survival in 332 patients with chronic lymphoid leukemia","volume":"123","author":"Falchi","year":"2014","journal-title":"Blood"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1474","DOI":"10.3109\/10428194.2015.1099643","article-title":"An 18F-FDG-PET maximum standardized uptake value > 10 represents a novel valid marker for discerning Richter\u2019s Syndrome","volume":"57","author":"Michallet","year":"2016","journal-title":"Leuk. Lymphoma"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1182\/blood.V130.Suppl_1.834.834","article-title":"Analysis of PET-CT to Identify Richter\u2019s Transformation in 167 Patients with Disease Progression Following Kinase Inhibitor Therapy","volume":"130","author":"Mato","year":"2017","journal-title":"Blood"},{"key":"ref_27","unstructured":"Armitage, J.O., Mauch, P.M., Harris, N.L., Coiffier, B., and Dalla-Favera, R. (2010). Non-Hodgkin Lymphomas, Lippincott Williams & Wilkins, a Wolters Kluwer Business. [2nd ed.]."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1097\/00000478-198812000-00002","article-title":"Paraimmunoblastic Variant of Small Lymphocytic Lymphoma\/Leukemia","volume":"12","author":"Pugh","year":"1988","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1526","DOI":"10.3324\/haematol.2010.022277","article-title":"Expanded and highly active proliferation centers identify a histological subtype of chronic lymphocytic leukemia (\u201caccelerated\u201d chronic lymphocytic leukemia) with aggressive clinical behavior","volume":"95","author":"Eva","year":"2010","journal-title":"Haematologica"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e1601","DOI":"10.1002\/cnr2.1601","article-title":"Atypical \u201caccelerated\u201d chronic lymphocytic leukemia with abnormal lymphocyte chromatin clumping, bone involvement, and exceptional response to Imbruvica","volume":"5","author":"Yavorkovsky","year":"2022","journal-title":"Cancer Rep."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2673","DOI":"10.1182\/blood-2013-03-489518","article-title":"Two main genetic pathways lead to the transformation of chronic lymphocytic leukemia to Richter syndrome","volume":"122","author":"Chigrinova","year":"2013","journal-title":"Blood"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1038\/nature10113","article-title":"Whole-genome sequencing identifies recurrent mutations in chronic lymphocytic leukaemia","volume":"475","author":"Puente","year":"2011","journal-title":"Nature"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1389","DOI":"10.1084\/jem.20110921","article-title":"Analysis of the chronic lymphocytic leukemia coding genome: Role of NOTCH1 mutational activation","volume":"208","author":"Fabbri","year":"2011","journal-title":"J. Exp. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3215","DOI":"10.1182\/blood-2016-01-688796","article-title":"The BCL2 selective inhibitor venetoclax induces rapid onset apoptosis of CLL cells in patients via a TP53-independent mechanism","volume":"127","author":"Anderson","year":"2016","journal-title":"Blood"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"765","DOI":"10.3324\/haematol.2019.224121","article-title":"Clinical characteristics and outcomes of Richter transformation: Experience of 204 patients from a single center","volume":"105","author":"Wang","year":"2020","journal-title":"Haematologica"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1002\/1097-0142(19900701)66:1<140::AID-CNCR2820660125>3.0.CO;2-I","article-title":"Single clonal origin of neoplastic B-cells with different immunoglobulin light chains in a patient with Richter\u2019s syndrome","volume":"66","author":"Miyamura","year":"1990","journal-title":"Cancer"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1097\/PAS.0000000000001077","article-title":"PD-1 Expression in Chronic Lymphocytic Leukemia\/Small Lymphocytic Lymphoma (CLL\/SLL) and Large B-cell Richter Transformation (DLBCL-RT): A Characteristic Feature of DLBCL-RT and Potential Surrogate Marker for Clonal Relatedness","volume":"42","author":"He","year":"2018","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"4179","DOI":"10.1182\/blood.V122.21.4179.4179","article-title":"Outcomes Of Chronic Lymphocytic Leukemia Patients With Richter Syndrome","volume":"122","author":"Parikh","year":"2013","journal-title":"Blood"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"E239","DOI":"10.1002\/ajh.23841","article-title":"Poor efficacy and tolerability of R-CHOP in relapsed\/refractory chronic lymphocytic leukemia and R ichter transformation","volume":"89","author":"Langerbeins","year":"2014","journal-title":"Am. J. Hematol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1111\/bjh.14177","article-title":"NCRI phase II study of CHOP in combination with ofatumumab in induction and maintenance in newly diagnosed Richter syndrome","volume":"175","author":"Eyre","year":"2016","journal-title":"Br. J. Haematol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"329","DOI":"10.3109\/10428190109064589","article-title":"Fractionated cyclophosphamide, vincristine, liposomal daunorubicin (daunoXome), and dexamethasone (hyperCVXD) regimen in Richter\u2019s syndrome","volume":"42","author":"Dabaja","year":"2001","journal-title":"Leuk. Lymphoma"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1711","DOI":"10.1002\/cncr.11238","article-title":"Fractionated cyclophosphamide, vincristine, liposomal daunorubicin, and dexamethasone plus rituximab and granulocyte-macrophage-colony stimulating factor (GM-CSF) alternating with methotrexate and cytarabine plus rituximab and GM-CSF in patients with Richter syndrome or fludarabine-refractory chronic lymphocytic leukemia","volume":"97","author":"Tsimberidou","year":"2003","journal-title":"Cancer"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1111\/bjh.15035","article-title":"A single-institution retrospective cohort study of first-line R-EPOCH chemoimmunotherapy for Richter syndrome demonstrating complex chronic lymphocytic leukaemia karyotype as an adverse prognostic factor","volume":"180","author":"Rogers","year":"2018","journal-title":"Br. J. Haematol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1200\/JCO.2007.11.8513","article-title":"Phase I-II study of oxaliplatin, fludarabine, cytarabine, and rituximab combination therapy in patients with Richter\u2019s syndrome or fludarabine-refractory chronic lymphocytic leukemia","volume":"26","author":"Tsimberidou","year":"2008","journal-title":"J. Clin. Oncol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1016\/j.clml.2013.03.012","article-title":"Phase I-II clinical trial of oxaliplatin, fludarabine, cytarabine, and rituximab therapy in aggressive relapsed\/refractory chronic lymphocytic leukemia or Richter syndrome","volume":"13","author":"Tsimberidou","year":"2013","journal-title":"Clin. Lymphoma Myeloma Leuk."},{"key":"ref_46","first-page":"93a","article-title":"Sequential cis-platinum, fludarabine, and arabinosyl cytosine (PFA) or cyclophosphamide, fludarabine and arabinosyl cytosine (CFA) in patients with Richter\u2019s syndrome","volume":"88","author":"Giles","year":"1996","journal-title":"Blood"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1080\/10428190290016872","article-title":"Phase II study of fludarabine, cytarabine (Ara-C), cyclophosphamide, cisplatin and GM-CSF (FACPGM) in patients with Richter\u2019s syndrome or refractory lymphoproliferative disorders","volume":"43","author":"Tsimberidou","year":"2002","journal-title":"Leuk. Lymphoma"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2211","DOI":"10.1200\/JCO.2011.37.4108","article-title":"Autologous and allogeneic stem-cell transplantation for transformed chronic lymphocytic leukemia (Richter\u2019s syndrome): A retrospective analysis from the chronic lymphocytic leukemia subcommittee of the chronic leukemia working party and lymphoma working party of the European Group for Blood and Marrow Transplantation","volume":"30","author":"Cwynarski","year":"2012","journal-title":"J. Clin. Oncol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"3528","DOI":"10.1182\/bloodadvances.2021004865","article-title":"Autologous and allogeneic hematopoietic cell transplantation for diffuse large B-cell lymphoma-type Richter syndrome","volume":"5","author":"Herrera","year":"2021","journal-title":"Blood Adv."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"3219","DOI":"10.3324\/haematol.2021.279033","article-title":"Allogeneic hematopoietic cell transplantation outcomes in patients with Richter\u2019s transformation","volume":"106","author":"Kim","year":"2021","journal-title":"Haematologica"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2879","DOI":"10.1182\/bloodadvances.2020003726","article-title":"Reduced-intensity conditioning hematopoietic stem cell transplantation for chronic lymphocytic leukemia and Richter\u2019s transformation","volume":"5","author":"Lahoud","year":"2021","journal-title":"Blood Adv."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1910","DOI":"10.1182\/blood-2017-10-810044","article-title":"Single-agent ibrutinib in treatment-naive and relapsed\/refractory chronic lymphocytic leukemia: A 5-year experience","volume":"131","author":"Furman","year":"2018","journal-title":"Blood"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2443","DOI":"10.1161\/CIRCULATIONAHA.120.049210","article-title":"Ibrutinib-Mediated Atrial Fibrillation Attributable to Inhibition of C-Terminal Src Kinase","volume":"142","author":"Xiao","year":"2020","journal-title":"Circulation"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2610","DOI":"10.1182\/bloodadvances.2017011999","article-title":"Severe platelet dysfunction in NHL patients receiving ibrutinib is absent in patients receiving acalabrutinib","volume":"1","author":"Bye","year":"2017","journal-title":"Blood Adv."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"3441","DOI":"10.1200\/JCO.21.01210","article-title":"Acalabrutinib Versus Ibrutinib in Previously Treated Chronic Lymphocytic Leukemia: Results of the First Randomized Phase III Trial","volume":"39","author":"Byrd","year":"2021","journal-title":"J. Clin. Oncol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1056\/NEJMoa2211582","article-title":"Zanubrutinib or Ibrutinib in Relapsed or Refractory Chronic Lymphocytic Leukemia","volume":"388","author":"Brown","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"892","DOI":"10.1016\/S0140-6736(21)00224-5","article-title":"Pirtobrutinib in relapsed or refractory B-cell malignancies (BRUIN): A phase 1\/2 study","volume":"397","author":"Mato","year":"2021","journal-title":"Lancet"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1182\/blood-2022-157058","article-title":"Efficacy of Pirtobrutinib, a Highly Selective, Non-Covalent (Reversible) BTK Inhibitor in Richter Transformation: Results from the Phase 1\/2 BRUIN Study","volume":"140","author":"Wierda","year":"2022","journal-title":"Blood"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2062","DOI":"10.1182\/blood-2014-09-603670","article-title":"Outcomes of patients with chronic lymphocytic leukemia after discontinuing ibrutinib","volume":"125","author":"Jain","year":"2015","journal-title":"Blood"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1182\/blood.V128.22.60.60","article-title":"Acalabrutinib Monotherapy in Patients with Richter Transformation from the Phase 1\/2 ACE-CL-001 Clinical Study","volume":"128","author":"Hillmen","year":"2016","journal-title":"Blood"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1676","DOI":"10.1182\/blood-2014-12-610782","article-title":"The efficacy of ibrutinib in the treatment of Richter syndrome","volume":"125","author":"Tsang","year":"2015","journal-title":"Blood"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2642","DOI":"10.1182\/bloodadvances.2019000360","article-title":"Distinct immune composition in lymph node and peripheral blood of CLL patients is reshaped during venetoclax treatment","volume":"3","author":"Hofland","year":"2019","journal-title":"Blood Adv."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"3419","DOI":"10.1182\/blood-2017-02-765685","article-title":"Pembrolizumab in patients with CLL and Richter transformation or with relapsed CLL","volume":"129","author":"Ding","year":"2017","journal-title":"Blood"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1242","DOI":"10.1016\/j.cell.2015.08.052","article-title":"Melanoma Cell-Intrinsic PD-1 Receptor Functions Promote Tumor Growth","volume":"162","author":"Kleffel","year":"2015","journal-title":"Cell"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"e117","DOI":"10.1111\/bjh.16762","article-title":"Pembrolizumab in relapsed or refractory Richter syndrome","volume":"190","author":"Armand","year":"2020","journal-title":"Br. J. Haematol."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Jain, N., Senapati, J., Thakral, B., Ferrajoli, A., Thompson, P.A., Burger, J.A., Basu, S., Kadia, T.M., Daver, N.G., and Borthakur, G. (2022). A Phase 2 Study of Nivolumab Combined with Ibrutinib in Patients with Diffuse Large B-cell Richter Transformation of CLL. Blood Adv.","DOI":"10.1182\/bloodadvances.2022008790"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1182\/blood-2018-99-117526","article-title":"Phase I\/II Study of Umbralisib (TGR-1202) in Combination with Ublituximab (TG-1101) and Pembrolizumab in Patients with Relapsed\/Refractory CLL and Richter\u2019s Transformation","volume":"132","author":"Mato","year":"2018","journal-title":"Blood"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"826","DOI":"10.1200\/JCO.2016.70.4320","article-title":"Phase I First-in-Human Study of Venetoclax in Patients With Relapsed or Refractory Non-Hodgkin Lymphoma","volume":"35","author":"Davids","year":"2017","journal-title":"J. Clin. Oncol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1182\/blood.2021011386","article-title":"Venetoclax plus dose-adjusted R-EPOCH for Richter syndrome","volume":"139","author":"Davids","year":"2022","journal-title":"Blood"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1097\/01.HS9.0000845488.18043.aa","article-title":"P651: Venetoclax-based treatment of patients with richter syndrome: Outcomes from a multicenter retrospective study","volume":"6","author":"Hampel","year":"2022","journal-title":"HemaSphere"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"2531","DOI":"10.1056\/NEJMoa1707447","article-title":"Axicabtagene Ciloleucel CAR T-Cell Therapy in Refractory Large B-Cell Lymphoma","volume":"377","author":"Neelapu","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1016\/S0140-6736(20)31366-0","article-title":"Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): A multicentre seamless design study","volume":"396","author":"Abramson","year":"2020","journal-title":"Lancet"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1056\/NEJMoa1804980","article-title":"Tisagenlecleucel in Adult Relapsed or Refractory Diffuse Large B-Cell Lymphoma","volume":"380","author":"Schuster","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"4648","DOI":"10.1182\/bloodadvances.2020002783","article-title":"Clinical activity of axicabtagene ciloleucel in adult patients with Richter syndrome","volume":"4","author":"Kittai","year":"2020","journal-title":"Blood Adv."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1182\/blood-2020-138904","article-title":"Safety and Efficacy of CD19-CAR T Cells in Richter\u2019s Transformation after Targeted Therapy for Chronic Lymphocytic Leukemia","volume":"136","author":"Benjamini","year":"2020","journal-title":"Blood"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"3010","DOI":"10.1200\/JCO.2017.72.8519","article-title":"Durable Molecular Remissions in Chronic Lymphocytic Leukemia Treated With CD19-Specific Chimeric Antigen Receptor\u2013Modified T Cells After Failure of Ibrutinib","volume":"35","author":"Turtle","year":"2017","journal-title":"J. Clin. Oncol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1182\/blood-2022-158298","article-title":"Subcutaneous Epcoritamab in Patients with Richter\u2019s Syndrome: Early Results from Phase 1b\/2 Trial (EPCORE CLL-1)","volume":"140","author":"Kater","year":"2022","journal-title":"Blood"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"2228","DOI":"10.1038\/s41375-022-01649-3","article-title":"A phase two study of high dose blinatumomab in Richter\u2019s syndrome","volume":"36","author":"Thompson","year":"2022","journal-title":"Leukemia"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"3570","DOI":"10.1182\/blood-2021-147467","article-title":"Blinatumomab for Patients with Richter\u2019s Syndrome: A Multicenter Phase 2 Trial from the Filo Group","volume":"138","author":"Guieze","year":"2021","journal-title":"Blood"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1056\/NEJMoa041511","article-title":"131I-Tositumomab Therapy as Initial Treatment for Follicular Lymphoma","volume":"352","author":"Kaminski","year":"2005","journal-title":"N. 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Rituximab\/BEAM and Autologous Stem Cell Transplantation for Relapsed Diffuse Large B-Cell Lymphoma (DLBCL): No Difference in Progression-Free (PFS) or Overall Survival (OS)","volume":"118","author":"Vose","year":"2011","journal-title":"Blood"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"2195","DOI":"10.1002\/cncr.20252","article-title":"Yttrium-90 ibritumomab tiuxetan radioimmunotherapy in Richter syndrome","volume":"100","author":"Tsimberidou","year":"2004","journal-title":"Cancer"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/15\/6\/1857\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:59:08Z","timestamp":1760122748000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/15\/6\/1857"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,20]]},"references-count":82,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2023,3]]}},"alternative-id":["cancers15061857"],"URL":"https:\/\/doi.org\/10.3390\/cancers15061857","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,20]]}}}