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Chronic Lymphocytic Leukemia A Clinical Review

Chadi Nabhan, MD1; Steven T. Rosen, MD2
[+] Author Affiliations
1Section of Hematology and Oncology, Department of Medicine, The University of Chicago Medicine, Chicago, Illinois
2City of Hope Comprehensive Cancer Center, Duarte, California
JAMA. 2014;312(21):2265-2276. doi:10.1001/jama.2014.14553.
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Importance  The most common leukemia is chronic lymphocytic leukemia (CLL). Every year, there are 15 000 new diagnoses and 5000 CLL deaths in the United States. Although therapeutic choices were once limited, treatment of this disease has vastly improved in the last decade.

Objective  Evidence-based review of the diagnosis, staging, and treatment of CLL.

Evidence Review  PubMed, Cochrane Library, Scopus, and Google Scholar databases were searched through August 28, 2014. English-language peer-reviewed articles published between 2000-2014 were found using the keywords chronic lymphocytic leukemia, upfront therapy, upfront therapies, upfront therapeutic, upfront therapeutics, upfront treatment, front-line treatment, first-line treatment, front-line treatments, first-line treatments, front-line therapy, front-line therapies, randomized, randomized studies, randomized study, clinical trial, clinical trials, phase 3, and phase 3 clinical trial. Abstracts and presentations at scientific meetings were excluded. A total of 277 articles were retrieved, of which 24 met our predefined selection criteria; treatment recommendations were based on subsequent analysis of these 24 articles.

Findings  The Rai and Binet systems for staging CLL were established in 1975 and 1977, respectively. However, they do not account for new disease categories such as monoclonal B-cell lymphocytosis (peripheral blood clonal lymphocytosis that does not meet other criteria for CLL). Two subsets of CLL are now recognized based on risk stratification involving molecular and cytogenetic analyses. Outcomes are improved by the addition of immunotherapy to combination chemotherapy for initial treatment in all subsets of treated patients. Overall response rates between 75% and 90% and complete responses between 22% and 45% are expected in the current era, with more than 80% of treated patients alive at 3 years. Overall, 5-year survival has increased to 66% from 60% (P < .001) in the past 10 years.

Conclusions and Relevance  Chemoimmunotherapy is the standard first-line option approach for CLL, the most common leukemia observed in adults. Treatment is initiated when the disease becomes symptomatic, and survival is high following treatment.

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Figure.
Characteristic Histologic Features and Immunophenotype of Chronic Lymphocytic Leukemia

A, Peripheral blood smear from a patient with chronic lymphocytic leukemia (CLL) that shows scattered smudge cells and small lymphoid cells with clumped chromatin typical of CLL (Wright-Giemsa, original magnification ×200). B, Histology of lymph node biopsy tissue from the same patient showing diffuse proliferation of small lymphoid cells with occasional pale areas corresponding to proliferation centers (hematoxylin-eosin, original magnification ×100). Inset shows a paraimmunoblast (large cell with prominent nucleoli) within 1 proliferation center (arrowhead) (hematoxylin-eosin, original magnification ×400). Flow cytometry plot (from a different patient with CLL) depicting CLL population in red expressing (C) CD19 (B-cell marker) and CD5, in addition to (D) CD23 with (E) lambda light chain restriction; nearly all CLL cells shown in red express uniform lambda light chain as depicted on the x-axis. All antigens are tagged with the depicted fluorochromes. The axis scales represent fluorescence intensity. FITC indicates fluorescein isothiocyanate; PE, phycoerythrin; ECD, electron coupled dye; PC5, phycoerythrin-cyanine 5. Figure courtesy of Girish Venkataraman, MD, Department of Pathology, University of Chicago.

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