**2.2. Alemtuzumab**

of different therapies and 4) major clinical trials evaluating the effectiveness of specific regimens. New emerging strategies and therapeutic agents that are being investigated will

The goal of induction therapy is to suppress both cellular and humoral responses to prevent episodes of acute rejection. Rabbit anti-thymocyte globulin (rATG), IL-2 receptor blockers, and Alemtuzumab (Campath), are the primary antilymphocyte antibody preparations that are currently used for induction. More than 80% of the transplant centers in the United States use induction agents immediately post transplantation.[3] The specific agent utilized is often based on multiple factors which include recipient risk for rejection, recipient race, presence of chronic infections such as Hepatitis B or C, HIV, and center preference. See Table 1. for common

Thymoglobulin (rATG) is the most commonly used induction agent in United States. (rATG), is an antilymphocyte polyclonal antibody that is derived by injecting rabbits with human thymocytes. rATG contains polyclonal cytotoxic antibodies mainly targeted against various epitopes on human T lymphocytes and works primarily by complement mediated depletion of T lymphocytes. However, the multiple specificities of rATG against a broad range of T-cell antigens can affect multiple pathways involved in T-cell trafficking, adhesion, activation and promotion of certain T-cell subsets that may be more favorable for transplantation such as Tregulatory cells. [4-6] Although primarily a T-cell directed agent, the development of humoral responses which are dependent on T-cell help are likely compromised by rATG as well.

Secondary to potential infusion reactions and other toxicities, administration of rATG requires patient monitoring and is administered in an inpatient setting or in an established infusion center. The typical dose is 1.5mg/kg/dose and involves 3-5 doses of rATG, depending on center

The antibodies in rATG can bind to proteins on the surface of granulocytes as well as platelets and hence leucopenia and thrombocytopenia are commonly encountered after rATG admin‐ istration. Cytopenias are handled either by dose reduction or holding the dose. Despite premedication, infusion reactions do occur including fevers, chills and arthralgias. Serious reactions such as anaphylaxis, acute respiratory distress syndrome (noncardiogenic pulmo‐ nary edema) occur rarely. Typically these reactions are a result of intense cytokine release from lysis of T lymphocytes. Since rATG is obtained from rabbit sera, serum sickness can occur which presents with fever, malaise, diffuse arthralgias and rash. rATG results in prolonged T cell depletion, up to 6 months post administration and recipients are at increased risk for

also be discussed.

induction agents.

*2.1.1. Side effects*

protocols.

**2.1. Thymoglobulin**

**2. Induction agents**

206 Current Issues and Future Direction in Kidney Transplantation

Alemtuzumab or Campath is a recombinant humanized monoclonal antibody directed against CD52. It binds to CD52 receptor on the surface of T and B lymphocytes leading to antibody mediated cell lysis. CD52 is present on virtually all B and T cells as well as macrophages, NK cells and some granulocytes. It was initially approved for use in B-cell lymphocytic leukemia and is now used in transplantation. Alemtuzumab induces a rapid and profound depletion of peripheral and central lymphoid cells. It is typically administered as a single 30 mg dose either subcutaneously or intravenously. Just like rATG patients receive premedication to prevent infusion reactions. When used as an induction agent it is given intraoperatively. Single dose administration makes Campath a more convenient option to administer compared to rATG which is typically administered daily for 3-5 days.
