{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T13:46:28Z","timestamp":1792071988885,"version":"4.4.0"},"reference-count":179,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2017,8,7]],"date-time":"2017-08-07T00:00:00Z","timestamp":1502064000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["KFO 286"],"award-info":[{"award-number":["KFO 286"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J Hematol"],"published-print":{"date-parts":[[2017,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Disease Overview<\/jats:title>\n                    <jats:p>Chronic lymphocytic leukemia (CLL) is the commonest leukemia in western countries. The disease typically occurs in elderly patients and has a highly variable clinical course. Leukemic transformation is initiated by specific genomic alterations that impair apoptosis of clonal B cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Diagnosis<\/jats:title>\n                    <jats:p>The diagnosis is established by blood counts, blood smears, and immunophenotyping of circulating B lymphocytes, which identify a clonal B\u2010cell population carrying the CD5 antigen and B\u2010cell markers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Prognosis<\/jats:title>\n                    <jats:p>\n                      Two prognostic staging systems exist, the Rai and Binet staging systems, which are established by physical examination and blood counts. Various biological and genetic markers also have prognostic value. Deletions of the short arm of chromosome 17 (\n                      <jats:italic>del(17p)<\/jats:italic>\n                      ) and\/or mutations of the TP53 gene predict resistance to available chemotherapies. A comprehensive prognostic score (CLL\u2010IPI) using genetic, biological, and clinical variables has recently been developed allowing to classify CLL into very distinct risk groups.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Therapy<\/jats:title>\n                    <jats:p>\n                      Patients with active or symptomatic disease or with advanced Binet or Rai stages require therapy. For physically fit patients, chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab remains the current standard therapy. For unfit patients, currently available evidence supports two options for a first\u2010line therapy: chlorambucil combined with an anti\u2010CD20 antibody (obinutuzumab or rituximab or ofatumumab) or a continuous therapy with ibrutinib. At relapse, the initial treatment may be repeated, if the treatment\u2010free interval exceeds 3\u00a0years. If the disease relapses earlier, therapy should be changed using alternative agents such as bendamustine (plus rituximab), alemtuzumab, lenalidomide, ofatumumab, ibrutinib, idelalisib, or venetoclax. Patients with a\n                      <jats:italic>del(17p)<\/jats:italic>\n                      or\n                      <jats:italic>TP53<\/jats:italic>\n                      mutation can be treated with ibrutinib, venetoclax, or a combination of idelalisib and rituximab. An allogeneic SCT may be considered in relapsing patients with\n                      <jats:italic>TP53<\/jats:italic>\n                      mutations or\n                      <jats:italic>del(17p)<\/jats:italic>\n                      or patients that are refractory to chemoimmunotherapy and the novel inhibitors.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Future Challenges<\/jats:title>\n                    <jats:p>The new agents (ibrutinib, idelalisib, venetoclax, and obinutuzumab) hold the potential to significantly improve the outcome of CLL patients. However, their optimal use (in terms of combination, sequence, and duration) remains unknown. Therefore, CLL patients should be treated in clinical trials whenever possible.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ajh.24826","type":"journal-article","created":{"date-parts":[[2017,8,7]],"date-time":"2017-08-07T07:45:17Z","timestamp":1502091917000},"page":"946-965","source":"Crossref","is-referenced-by-count":233,"title":["Chronic lymphocytic leukemia: 2017 update on diagnosis, risk stratification, and treatment"],"prefix":"10.1002","volume":"92","author":[{"given":"Michael","family":"Hallek","sequence":"first","affiliation":[{"name":"Department I of Internal Medicine Center for Integrated Oncology K\u00f6ln Bonn, Center of Excellence on \u201cCellular Stress Responses in Aging\u2010Associated Diseases,\u201d University of Cologne Kerpener Strasse 62 K\u00f6ln 50937 Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,8,7]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/canjclin.57.1.43"},{"key":"e_1_2_9_3_1","unstructured":"National Cancer Institute [Website]. 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