{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T19:22:44Z","timestamp":1790882564369,"version":"4.1.0"},"reference-count":146,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2016,2,22]],"date-time":"2016-02-22T00:00:00Z","timestamp":1456099200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J Hematol"],"published-print":{"date-parts":[[2016,3]]},"abstract":"<jats:p>The field of chronic lymphocytic leukemia (CLL) has witnessed considerable change since the time clinical staging was introduced in clinical practice in 1975. Over the years, the prognostication in CLL has expanded with the addition in late 90s of mutational status of variable region of immunoglobulin heavy chain (IGHV), and chromosomal analyses using fluorescent in situ hybridization (FISH). More recently, stereotypy of BCR (B cell receptor) and whole exome sequencing (WES) based discovery of specific mutations such as <jats:italic>NOTCH1, TP53, SF3B1, XPO\u20101, BIRC3, ATM,<\/jats:italic> and <jats:italic>RPS15<\/jats:italic> further refined the current prognostication system in CLL. In therapy, the field of CLL has seen major changes from oral chlorambucil and steroids prior to 1980s, to chemo\u2010immunotherapy (CIT) with fludarabine, cyclophosphamide, rituximab (FCR) to the orally administered targeted therapeutic agents inhibiting kinases in the B cell receptor (BCR) signaling pathway such as Ibrutinib (BTK inhibitor) and Idelalisib (p110 PI3K\u03b4 inhibitor) and novel anti\u2010CD20 mAb's (monoclonal antibodies) such as obinutuzumab. This progress is continuing and other targeted therapeutics such as Bcl2 antagonists (Venetoclax or ABT\u2010199) and finally chimeric antigen receptor against T cells (CART) are in the process of being developed. This review is an attempt to summarize the major benchmarks in the prognostication and in the therapy of CLL. The topic allocated to us by Dr Ayalew Tefferi and Dr Carlo Brugnara is very appropriate to reminisce what our understanding of chronic lymphocytic leukemia (CLL) was in 1976 and how rapidly have the advances occurring in this field affected the patients with CLL. Am. J. Hematol. 91:330\u2013340, 2016. \u00a9 2015 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/ajh.24282","type":"journal-article","created":{"date-parts":[[2015,12,21]],"date-time":"2015-12-21T23:54:44Z","timestamp":1450742084000},"page":"330-340","source":"Crossref","is-referenced-by-count":131,"title":["<scp>C<\/scp>hronic lymphocytic leukemia (CLL)\u2014<scp>T<\/scp>hen and now"],"prefix":"10.1002","volume":"91","author":[{"given":"Kanti R.","family":"Rai","sequence":"first","affiliation":[{"name":"Division of Hematology\u2013Oncology, NSLIJ\u2010Hofstra School of Medicine, Long Island Jewish Medical Center CLL Research and Treatment Program New Hyde Park New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Preetesh","family":"Jain","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine University of Texas Medical School at Houston  Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,2,22]]},"reference":[{"key":"e_1_2_9_2_1","first-page":"1005","article-title":"The pathogenesis of chronic lymphocytic leukemia","volume":"94","author":"Galton DA.","year":"1966","journal-title":"Can Med Assoc J"},{"key":"e_1_2_9_3_1","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1182\/blood.V29.4.566.566","article-title":"Chronic lymphocytic leukemia\u2014An accumulative disease of immunolgically incompetent lymphocytes","volume":"29","author":"Dameshek W.","year":"1967","journal-title":"Blood"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.2.4949.1172"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.1961.tb00321.x"},{"key":"e_1_2_9_6_1","first-page":"17","article-title":"Treatment of chronic lymphatic leukemia with a new alkylating agent, cyclophosphamide","volume":"91","author":"Farrerasvalenti P","year":"1963","journal-title":"Rev Clin Esp"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-06-093906"},{"key":"e_1_2_9_8_1","unstructured":"National Cancer Institute.Available at:http:\/\/seer.cancer.gov\/csr\/1975_2007\/(accessed October 17. 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