Chapter 11: Chronic Lymphocytic Leukemia

Epidemiology

Work-up

Essential

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

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 with contrast of diagnostic quality prior to initiation of therapy

6. Hepatitis B testing if CD20 monoclonal antibody contemplated

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

8. Unilateral bone marrow biopsy + aspirate at initiation of therapy

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

10. PET/CT scan to direct nodal biopsy, if histologic transformation is suspected

11. Discussion of sperm banking and fertility issues

Informative for prognostic and/or therapy determination

1. CpG-stimulated metaphase karyotype

2. FISH analysis to detect: +12, del(11q), del(13q), del(17p)

3. TP53 sequencing

4. Molecular analysis to detect immunoglobulin heavy-chain variable gene (IGHV) mutation status

Diagnosis

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

Prognosis

Unfavorable risk factors

1. Advanced clinical stage

2. Rapid lymphocyte doubling time (<6 months)

3. TP53 mutation by DNA sequencing, and/or del(17p)

4. Unmutated IGHV genes (≤2 % mutation)

5. Diffuse bone marrow lymphocytic involvement

6. del(11q) by interphase (FISH) cytogenetics (normal karyotype and trisomy 12 have an intermediate prognosis, while 13q deletion has a good prognosis)^✫

7. Complex karyotype (≥3 unrelated) on conventional karyotyping

8. CD38 (>30%), ZAP-70 expression (>20%), CD49d (>30%) measured via flow cytometry

^✫Döehner H et al. N Engl J Med 2000;343:1910–1916

Staging and Survival