NOTE: * Anemia and thrombocytopenia are not immune-mediated.

    A frequent cause of morbidity and mortality are infections related to hypogammaglobulinemia. The most common bacterial pathogens are Streptococcus pneumoniae, Staphylococcus aureus, and Haemophilus influenzae; however, particularly after chemotherapy there is an increased risk of candidiasis, listeriosis, Pneumocystis jiroveci, and herpes virus infections such as CMV and HSV. All fevers must be taken seriously with appropriate diagnostic testing. Patients receiving highly immunosuppressive regimens should be monitored for CMV reactivation, but prophylactic intravenous immunoglobulins are reserved for patients with recurrent bacterial infections.

    Coombs’ positive hemolytic anemia and/or immune thrombocytopenia occur in about 20% of patients. These sometimes develop after the initiation of therapy and reflect immunologic dysregulation, since the clone does not produce the antibodies. Failure of immune surveillance results in an increased risk of solid tumors such as skin and colon cancers. Moreover, transformation to large-cell lymphoma (so-called Richter transformation) occurs in 15% of patients. It is heralded by increasing lymphadenopathy, hepatosplenomegaly, fever, abdominal pain, weight loss, anemia, and thrombocytopenia with a rapid rise in lactate dehydrogenase (LDH), and it has a poor prognosis.

RELATED B-CELL LEUKEMIAS

Two additional B-cell leukemias—prolymphocytic leukemia and hairy cell leukemia—although rare, should be considered in the differential diagnosis of CLL. Prolymphocytic leukemia may be of either B-cell or T-cell lineage. It occurs in somewhat older patients than CLL and tends to be more advanced at presentation. Symptoms include weight loss, fevers, and abdominal pain from splenomegaly. The white count tends to be quite high, and the smear is characteristically different from CLL—the cells are larger with a more prominent nucleolus. The immunophenotype distinguishes it from CLL by virtue of stronger expression of surface immunoglobulins, and they are less likely to express CD5. This disease responds poorly to therapy with a median survival of 1–3 years.

    Hairy cell leukemia is rarer than CLL and has a strong male predominance. Patients often have symptoms related to marrow depression with little in the way of leukocytosis, although characteristic hairy cells are usually seen in the blood. Like CLL, the cells express the B-cell antigens CD19 and CD20, but also the monocyte antigen CD11c and, characteristically, CD103. Treatment is indicated in the setting of massive or progressive splenomegaly, serious cytopenias, recurrent infections, or bulky lymphadenopathy. The purine analogues cladribine (Leukostatin) and pentostatin (Nipent) are extremely effective, resulting in long-term remissions in 70–80% of patients with little disease-related mortality.

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