Allergic reaction to chlorambucil in chronic lymphocytic leukemia presenting with fever and lymphadenopathy

Chronic lymphocytic leukemia (CLL) is commonly treated with the alkylating agent chlorambucil. Allergic reactions to this chemotherapy are rare. Previous reports include urticaria, angioedema, rashes, toxic epidermal necrolysis, drug fever and one case of immune hemolytic anemia. We report 2 cases that had the identical symptoms of acute onset of high fever and progressive lymphadenopathy. These symptoms disappeared with conservative management. Neither of the patients were treated for infection or disease progression. When the patients were rechallenged with chlorambucil, identical reactions recurred. There was no cross-reactivity with the alkylating agent cyclophosphamide or other types of chemotherapy. This type of reaction to chlorambucil has not been described previously. It is important to recognize this as an allergic reaction. These reactions could be confused with the onset of infection, progression of disease or even a Richter's transformation.