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Incidence: 15,720 (male: 9,100; female: 6,620. Estimated new cases for 2014 in the United States) 4.3 per 100,000 male and female per year (5.9 per 100,000 male, 3.1 per 100,000 female) Stage at Presentation (Rai):
Stage 0: 31%
Stage I/II: 59%
Deaths: Estimated 4,600 in 2014 (male: 2,800; female: 1,800) Stages III/IV: 10%
Median age: 70 years
Male to female ratio: 1.3:1

Siegel R et al. CA Cancer J Clin 2014;64:9–29

Surveillance, Epidemiology and End Results (SEER) Program, available from (accessed in 2013)




  1. Medical history and PE: attention to node-bearing areas, including the Waldeyer ring, and to size of liver and spleen

  2. Performance status

  3. B-symptoms

  4. Laboratory work-up: CBC with differential, LDH, comprehensive metabolic panel

  5. Hepatitis B testing if CD20 monoclonal antibody contemplated

  6. MUGA scan/echocardiogram if anthracycline-based regimen is indicated

  7. Pregnancy testing in women of child-bearing age (if chemotherapy planned)

  8. Unilateral bone marrow biopsy + aspirate


Useful in certain circumstances

  1. Quantitative immunoglobulins

  2. β2-Microglobulin

  3. Reticulocyte count, haptoglobin, direct Coombs test

  4. Uric acid

  5. Chest, abdomen, and pelvis CT scans prior to initiation of therapy


Informative for prognostic and/or therapy determination

  1. Cytogenetics/FISH analysis to detect: t(11q;v), +12, del(11q), del(13q), del(17p)

  2. Determination of CD38 and Zap 70 expression

  3. Immunoglobulin heavy-chain variable gene (IGHV) mutation status



NCI-working group diagnostic criteria

  1. Absolute lymphocytosis in the peripheral blood with a count of ≥5 × 109 B lymphocytes and cells morphologically mature in appearance

  2. The clonality of the B cells must be confirmed by flow cytometry

  3. The monoclonal B-cell lymphocytes express low levels of surface immunoglobulins, simultaneously with CD5, CD23, CD19, and CD20


Hallek M et al. Blood 2008;111:5446–5456



Poor risk factors

  1. Advanced clinical stage

  2. Rapid lymphocyte doubling time (<6 months)

  3. Diffuse bone marrow involvement

  4. High LDH, β2-microglobulin

  5. 17p and 11q deletions (normal karyotype and trisomy 12 have an intermediate prognosis, while 13q deletion has a good prognosis)

  6. Expression of CD38 (>30%)

  7. Unmutated IGHV genes

  8. Zap-70 expression (>30%)


Staging and Survival

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Staging and Survival

Kay NE et al. Hematology Am Soc Hematol Educ Program 2002:193–213

Rai Lymphocytosis Lymph Node Enlargement Spleen/Liver Enlargement Hemoglobin <11 g/dL Platelets <100,000/mm3 Survival Years
0 Yes No No No No >13
I Yes Yes No No No 8
II Yes ± Yes No No 6
III Yes ± ± Yes No 4
IV Yes ± ± ± Yes 2

Not immune-related


Expert Opinion


Chronic lymphocytic leukemia (CLL) is one of the most common leukemias in the Western world, characterized by the monoclonal proliferation of mature B lymphocytes in the blood, lymph nodes, and marrow. The diagnosis requires a count of over 5000 circulating CLL type cells per cubic millimeter. The median overall survival in patients with CLL is about 10 ...

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