Monoclonal antibodies in combination with chemotherapy and other agents have shown promise in the treatment of chronic lymphocytic leukemia (CLL). Alemtuzumab (Campath®), a humanized monoclonal antibody that targets the CD52 antigen, can effectively increase response rates in pretreated patients by inducing minimal residual disease (MRD) negative remission (

Moreton P, et al. J Clin Oncol. 2005;23:2971–2979
). Alemtuzumab has been shown to be an effective treatment for patients with fludarabine-refractory CLL (
Keating MJ, et al. Blood. 2002;99:3554–3561
). In this case study, alemtuzumab was used to treat a 41-year old male patient with CLL refractory to chlorambucil and fludarabine. The patient presented with generalized lymphadenomegaly (a left supraclavicular lymph node 4 cm), splenomegaly, and lymphocytosis. He had elevated beta 2-microglobulin and normal lactate dehydrogenase. Bone marrow aspirates showed marked lymphocytosis about 70%, and 30% of normal residual hematopoiesis. Flow cytometry revealed that 65% of the patient’s bone marrow cells coexpressed CD5 and CD23. He was diagnosed with Rai stage II and Binet stage B CLL. He was randomized to an EORTC trial and treated with high dose chlorambucil (HDCLB) for 24 weeks, which resulted in a partial response (PR). The disease progressed within the next 25 months, and the patient was retreated with HDCLB (September 2001 to March 2002), which resulted in a PR and CTC grade 4 thrombocytopenia. Within 6 months the patient relapsed, and was treated in September 2002 with fludarabine (40 mg/m2) administered orally on Days 1-5 every 28 days. After 4 cycles, the patient was determined to be resistant to fludarabine, based on unchanged absolute lymphocyte count (ALC) and size of lymph nodes and spleen, and was recommended for alemtuzumab therapy. In March 2003, alemtuzumab 30 mg/day tiw was administered for 12 weeks, which resulted in a complete response (CR) according to NCI criteria (ALC became zero, platelet counts normalized, the size of lymph nodes and spleen normalized, and the spleen was no longer palpable). The patient maintained a CR for 11 months before relapse. The patient was retreated with alemtuzumab for 4 weeks and achieved a PR (ALC became zero, platelet count normalized, the lymph nodes and the spleen remained palpable), but relapsed 3 months later. Peripheral blood cytogenetics (conventional and fluorescence in situ hybridization) revealed an 11q deletion, and 22% and 38% of cells expressed ZAP 70 and CD38, respectively. In March 2005, the patient received alemtuzumab for 12 weeks, which resulted in the patient achieving a CR with an ALC of zero, elevated platelet count, normalization of lymph node and spleen size, and CD5 and CD23 coexpression by 0.4% of cells in bone marrow. Based on this case, we recommend alemtuzumab retreatment for patients with fludarabine-resistant CLL. Further study is warranted to assess the long-term effect of using alemtuzumab in this type of modality.

Topics:
alemtuzumab, chemotherapy regimen, fludarabine, cd23 antigen, chlorambucil, lymphocytosis, monoclonal antibodies, beta 2-microglobulin, bone marrow aspiration, cd52 antigen

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2005, The American Society of Hematology
2005
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