Heterogeneous CD52 expression among hematologic neoplasms: Implications for the use of alemtuzumab (CAMPATH-1H)

Purpose: CD52 is a GPI-linked glycoprotein expressed by B cells, T cells, monocytes, and macrophages. The humanized monoclonal antibody alemtuzumab (CAMPATH-1H) is specific for CD52 and is Food and Drug Administration - approved for the treatment of relapsed or refractory chronic lymphocytic leukemia (CLL). The utility of CAMPATH in the treatment of other hematologic neoplasms has been explored; however, a comprehensive survey of CD52 expression among a broad spectrum of WHO-defined tumor types has not been completed. Experimental Design: We evaluated 294 hematologic neoplasms for the presence of CD52 using standard immunohistochemical techniques on paraffin-embedded biopsy specimens fixed with formalin, B-Plus, Zenker's acetic acid, or B5-formalin. Results: The vast majority of low-grade B cell lymphoproliferative disorders (CLL/small lymphocytic leukemia, follicular lymphoma, lymphoplasmacytic lymphoma, hairy cell leukemia, and mucosa-associated lymphoid tissue lymphomas) express CD52. In addition, we found that the majority of precursor B cell acute lymphoblastic leukemia/lymphomas express this antigen. In contrast, there is surprising heterogeneity in CD52 expression among more aggressive B cell lymphomas, with 25% of cases of diffuse large B cell lymphoma and Burkitt lymphoma demonstrating no detectable CD52. In addition, the majority of neoplasms of the T cell lineage are negative for the antigen, including most cases of precursor T cell acute lymphoblastic leukemia/ lymphoma, anaplastic large cell lymphoma, and peripheral T cell lymphoma, not otherwise specified. Finally, the vast majority of cases of acute myeloid leukemia, Hodgkin lymphoma, and multiple myeloma are negative for CD52 expression. Conclusion: In contrast with CLL, the variable expression of CD52 among other hematologic malignancies suggests that target validation on a case-by-case basis will likely be necessary to guide the rational analysis of CAMPATH therapy.