Infectious toxicity using alemtuzumab Alemtuzumab is a humanized monoclonal antibody directed against CD52, a non-modulating glycosylated peptide antigen that is highly expressed on B-cell in chronic lymphocytic leukemia (CLL) and on normal lym-

Alemtuzumab is a humanized monoclonal antibody directed against CD52, a non-modulating glycosylated peptide antigen that is highly expressed on B-cell in chronic lymphocytic leukemia (CLL) and on normal lymphocytes. CD52 is expressed on virtually all lymphocytes at various stages of differentiation, as well as on monocytes, macrophages and eosinophils; it is not expressed on granulocytes (<5%) or hematopoietic CD34 stem cells. The highest levels seem to be expressed on T-prolymphocytic leukemia (PLL) cells, followed by B-cell CLL, with the lowest levels on normal B cells. After binding to target cells alemtuzumab may cause cell death through host-effector mechanisms, such as antibodydependent cellular cytotoxicity, complement-mediated cytolysis and induction of apoptosis and it may also sensitize tumor cells to chemotherapy. Alemtuzumab has been extensively used to prevent graft-versus-host disease in allogeneic stem cell transplantation. It has been employed in CLL, and promising results were obtained in refractory/relapsed patients. More recently alemtuzumab has been used as first-line therapy for CLL, obtaining results similar to those provided by fludarabine or cladribine, with a pronounced effect on bone marrow and long-lasting remissions. The profound and long-lasting lymphocytolysis caused by alemtuzumab is also responsible for severe and prolonged immunodepression which produces a major predisposition to infectious complications. Obviously, the risk and the type of infection differ according to the indications for using this antibody and its doses; its association with chemotherapy, the use as conditioning regimen, in myeloablative and non-myeloablative transplantation, the concomitant administration of immunosuppressive drugs, and the characteristics of CLL itself can greatly change the severity of immunodepression, favoring those particular opportunistic infections associated with a low CD4 cell level (<50×10/L). However, because the number of treated patients has so far been low, and above all perspective studies have not been performed, it is difficult to correctly define the profile of infectious toxicity although this complication is beginning to emerge clearly.