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Answer 2
  1. Chlorambucil or another alkylating agent. This patient has developed symptomatic WM requiring therapy. Given the severity of this patient’s symptoms, observation alone would be inappropriate. With anemia and a positive Coombs’ test in this patient, cold agglutinin syndrome2 or warm antibody-mediated autoimmune hemolytic anemia (AIHA) should be considered. Although fludarabine or other purine analogues are used to treat WM, a patient with a positive baseline Coombs’ test may be at risk for a life-threatening exacerbation of AIHA following treatment with these agents, as has been described in patients with chronic lymphocytic leukemia.3 Chlorambucil would be a reasonable alternative, as up to 60% of patients with WM respond to this therapy.2 Compared with chlorambucil monotherapy, treatment with multidrug combinations does not improve outcomes and may increase toxicity. Prednisone 1 mg/kg/day would likely be helpful for treatment of AIHA but would not adequately address the patient’s other symptoms, such as splenomegaly.

    2.  Johnson SA, Birchall J, Luckie C, et al; Haemato-Oncology Task Force of the British Committee for Standards in Haematology. Guidelines on the management of Waldenström macroglobulinaemia. Br J Haematol 2006;132:683-97.

    3. Weiss RB, Freiman J, Kweder SL, et al. Hemolytic anemia after fludarabine therapy for chronic lymphocytic leukemia. J Clin Oncol 1998;16:1885-9.

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