Delayed Onset of Autoimmune Hemolytic Anemia Complicating Cladribine Therapy for Waldenström Macroglobulinemia

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Abstract
Therapeutic options for patients with Waldenström macroglobulinemia (WM) now include the purine nucleoside analogues, fludarabine and cladribine. Both these agents have been associated with the onset of severe life-threatening autoimmune hemolytic anemia (AIHA) in patients with chronic lymphocytic leukemia (CLL). In these reports, AIHA developed within 6 weeks of drug administration and was generally resistant to conventional therapy. AIHA following purine analogues has not been reported in other hematologic malignancies. We report here on 4 patients with WM who developed AIHA following cladribine therapy. Cladribine was administered as a 2-hour infusion at a dose of 0.12 mg/kg per day for 5 consecutive days, at 28-day intervals. The median number of cycles was four (range, 4 to 6). AIHA occurred at a median of 40 months (range, 24 to 60) from cladribine administration. Only 1 patient responded to oral steroids while the other 3 were resistant to multiple therapeutic interventions. Two patients, 1 in complete remission and 1 requiring transfusional support, remain alive, and 2 have died. In contrast to published reports of the early onset of AIHA occurring after purine analogues in CLL patients, we observed AIHA in WM patients as a delayed event.