Ann IM 2006;145:434; Nejm 2005;352:804

Cause:Genetic mutations

Pathophys: B-cell leukemia. Platelets decreased due both to autoimmune and splenomegaly mechanisms

Adults; M > F; 90% age 50+ yr, median age at onset = 65 yr; very rare in Asians; 10 000-15 000/yr US incidence

Sx:Onset insidious, asx for years; rash and/or ulcer

Si:

Stage 0: lymphocytosis >15 000

Stage I: above + adenopathy

Stage II: above + hepato- and/or splenomegaly

Stage III: above + anemia

Stage IV: above + depressed platelets (purpura)

Correlates with abnormal karyotypes (Nejm 2000;343:1910). 75% are stage 0 and 12% are stage I at presentation and have a 10-yr prognosis, though about half have aggressive disease and die w/i 8 yr and other half live twice as long (Nejm 1998;338:1506)

Table 8.1 Rai Staging (Nejm 1998;338:1506)

2nd malignancy; sepsis, esp with encapsulated organisms like H. flu and pneumococcus; ichthyosis; cardiac involvement (25%) rarely diagnosed premortem

r/o: other rare B-cell as well as T-cell types; often associated with retrovirus infections (Nejm 1995;332:1744, 1749) or SÉZARY SYNDROME from chromosome 14 inversion (Nejm 1986;314:865), the only type that involves the skin (Ann IM 1974;80:685)

Lab:

Chem:Elevated uric acid

Hem:NCNC anemia in 2/3; Coomb's-positive, steroid-responsive anemia in 1/3 (C. Finch, 1969); thrombocytopenia; wbc's >15 000, by definition, usually >100 000 with 75-90% lymphs, prolymphocytic variant may have up to 54% prolymphocytes but if more than that is prolymphocytic CLL w a bad prognosis; marrow shows monotonous lymphocytic infiltration. Flow cytometry to id monoclonal surface markers. CD5 markers on cells identify B-cell CLL and r/o reactive lymphocytosis

Rx:Only if sx or progression beyond stage I or II; in future will base rx on cell markers/mutations

Prophylactic pneumovax; rapid antibiotic rx of infections

Chemotherapy (www.nccn.org) for stage II+-III+ only, no help for stages 0, I and II unless progressive (Nejm 2000;343:1799; 1998;338:1506); usually with fludarabine (Nejm 2000;343:1750), rituximab, cyclophosphamide, pentostatin, and/or chlorambucil