Snapshot A 62-year-old Caucasian man complains of months of fatigue. He notices that his skin seems abnormally yellow. On physical exam, he has notable tender lymphadenopathy. Peripheral smear reveals some spherocytes and lymphocytosis. His leukocyte count is 35,000/μL with 95% lymphocytes and a Hb of 7 g/dL. His direct Coombs test is positive with anti-IgG. He is started on fludarabine. Introduction Clonal proliferation of incompetent B-cells small lymphocytic lymphoma (SLL) disease is mainly in lymph nodes chronic lymphocytic lymphoma (CLL) disease in blood and bone marrow Many are diagnosed incidentally with markedly elevated WBC Insidious onset of symptoms Epidemiology > 60 years of age Most common form of leukemia in adults in Western countries More common in Caucasian males ETIOLOGY Associated conditions warm autoimmune hemolytic anemia (IgG) Presentation Symptoms many are asymptomatic at presentation most common symptom is fatigue recurring infections from incompetent lymphocytes pneumonia zoster early satiety mucocutaneous bleeding from thrombocytopenia Physical exam painful lymphadenopathy hepatosplenomegaly STUDIES Labs – CBC ↑ WBC (> 20,000/μL) with > 80% lymphocytes ↓ RBCs (attacked by CLL cells) ↓ PLTs (attacked by CLL cells) ↓ IgG in half of patients Most accurate test flow cytometry – CD5, CD19, CD20, and CD23+ B-cells Peripheral blood smear smudge cells = hallmark artifact of lab, from cover slip crushing the nucleus Differential Diagnosis AIHA Mantle cell lymphoma ALL Hairy cell lymphoma Treatment Treatment only for symptomatic or rapid progression fludarabine – first-line fludarabine plus rituximab for symptomatic patients Curative therapy allogeneic stem cell transplant Complications Richter syndrome/transformation transformation of CLL into aggressive large B-cell lymphoma 3-10% of cases weight loss, fevers, night sweats, cachexia, and lymphadenopathy poor prognosis Infections secondary to hypogammaglobulinemia Prognosis Most live 5-10 years after diagnosis Some die rapidly, within 2-3 years