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

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.