Alemtuzumab is a humanized monoclonal antibody that targets the CD52 antigen. CD52 is abundantly expressed on leukemic B-CLL cells (approximately 4 x 105 binding sites/B-CLL cell) and to a lesser degree on normal B and T cells, which may result in pronounced immunosuppression. Treatment with alemtuzumab has achieved an ORR of 33% in patients with fludarabine refractory B-CLL (

Keating et al. J Clin Oncol. 2002;20:205–213
) and >80% in patients with symptomatic but previously untreated B-CLL (
Lundin et al. Blood. 2002;100:768–773
). Progressive B-CLL is frequently complicated by autoimmune complications such as autoimmune hemolytic anemia (AIHA), which is estimated to occur in 10% to 20% of patients. We report here on 5 patients with advanced B-CLL and 1 with hairy cell leukemia (earlier diagnosed as B-CLL), all of whom developed severe AIHA resistant to conventional therapy (eg, corticosteroids, rituximab, chemotherapy, etc.) that received alemtuzumab as salvage treatment for AIHA. The median age of patients was 66 years (range, 59–77 years). At the start of alemtuzumab therapy, all patients had disease classified as Rai stage III or IV, were heavily pretreated with chemotherapy, and had severe transfusion dependent DAT-positive AIHA, which was resistant to conventional AIHA therapy, with a median Hb of 7.8 g/dL. The alemtuzumab dose was quickly escalated to 30 mg SC tiw (n = 3) or IV (n = 3), and continued for a median treatment period of 4 weeks (range, 3–8 weeks). Of 6 patients who received alemtuzumab, 5 responded with a >2 g/dL rise in Hb concentration, which eliminated the need for transfusion after a median of 3 weeks (range, 2–8 weeks). At the end of therapy, the median Hb concentration in the responding patients was 122 g/dL (range, 100–125 g/dL). Alemtuzumab was well tolerated with only minor “first-dose” reactions. However, 1 patient had a CMV reactivation, as indicated by a fever of unknown origin that responded rapidly to foscarnet. All patients were alive at a median follow-up time of 5 months, and none of the responding patients experienced another episode of AIHA. We conclude that alemtuzumab may be an important therapeutic option for patients with severe, refractory CLL-related AIHA, who have not previously responded to conventional treatment.

Topics:
alemtuzumab, autoimmune hemolytic anemia, monoclonal antibodies, chemotherapy regimen, transfusion, adrenal corticosteroids, cd52 antigen, cmv reactivation, fever of unknown origin, fludarabine

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2005, The American Society of Hematology
2005
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