Leukemia chronic lymphocytic, treatment

This is a humanized anti-CD52 monoclonal antibody. At present it is in clinical use after bone marrow transplantation and for the treatment of refractory chronic lymphocytic leukemia. 

Alemtuzumab is the antibody to the CD52 receptor present on B and T lymphocytes. The pharmacokinetics of alemtuzumab demonstrate a terminal half-life of 7 days. Alemtuzumab has shown clinical activity in the treatment of chronic lymphocytic leukemia. Severe and prolonged (6 months) immunosuppression may result, which necessitates prophylaxis with cotrimox-azole and antivirals to prevent opportunistic infections. 

Describe patients who may be observed without treatment and those who receive aggressive treatment for chronic lymphocytic leukemia (CLL). 

Ferrajoli A, O Brien SM. Treatment of chronic lymphocytic leukemia. Semin Oncol 2004 31 60-65. 

Intravenous Immune Globulin (IGIV) IGIV is a product derived from blood plasma from a donor pool similar to the immune globulin (IG) pool, but prepared so it is suitable for intravenous use. IGIV does not transmit infectious diseases. It is primarily used for replacement therapy in primary antibody-deficiency disorders, for the treatment of Kawasaki disease, immune thrombocytopenic purpura, hypogammaglobulinemia in chronic lymphocytic leukemia, and in some cases of HIV infection. 

Hainsworth, J.D., Litchy, S., Barton, J.H., Houston, G.A., Hermann, R.C., Bradof, J.E., and Greco, RA., Single-agent rituximab as first-line and maintenance treatment for patients with chronic lymphocytic leukemia or small lymphocytic lymphoma a phase II trial of the Minnie Pearl Gancer Research Network, /. Clin. Oncol., 21,1746-2751, 2003. 

Hayden RE, Pratt G, Roberts C et al (2011) Treatment of chronic lymphocytic leukemia requires targeting of the protective lymph node environment with novel therapeutic approaches. Leuk Lymphoma 53(4) 537-549... 

Alemtuzumab is a recombinant DNA-derived humanized monoclonal antibody used in the treatment of chronic lymphocytic leukemia and T-cell lymphoma. It targets CD52, a protein present on the surface of mature lymphocytes. Alemtuzumab has been associated with infusion-related events including hypotension, rigors, fever, shortness of breath, bron-chospasm, chills, and/or rash. Also reported were syncope, pulmonary infiltrates, cardiac arrhythmias, myocardial infarction and cardiac arrest. 

The drug is highly active in the treatment of chronic lymphocytic leukemia, with approximately 40% of patients achieving remissions after previous therapy with alkylating agents has failed. Activity is also seen in the low-grade lymphomas. 

Indications Treatment of patients with B-cell chronic lymphocytic leukemia who... 

B. Indications and nse Campath is indicated for the treatment of B-cell chronic lymphocytic leukemia (B-CLL) in patients who have been treated with alkylating agents and who have failed fludarabine therapy. Determination of the effectiveness of Campath is based on overall response rates. Comparative randomized trials demonstrating increased survival or clinical benefits such as improvement in disease-related symptoms have not yet been conducted. 

Treatment of patients with B-cell chronic lymphocytic leukemia who have been treated with alkylating agents and who have failed fludarabine therapy... 

This chapter reviews our current understanding of the mechanism of action of monoclonal antibody (especially rituximab), as well as the role of Fey receptor and Fey receptor gene polymorphisms, and their impact on treatment outcomes in hematologic malignancies including follicular lymphoma (FL), diffuse large B-cell lymphoma (DL-BCL), Waldenstrom s macroglobulinemia (WM), and chronic lymphocytic leukemia (CLL). 

NK cells, monocytes, macrophages, and a small population of granulocytes. Currently, alemtuzumab is approved for the treatment of -cell chronic lymphocytic leukemia in patients who have been treated with alkylating agents and have failed fludarabine therapy. Alemtuzumab appears to deplete leukemic and normal cells by direct antibody-dependent lysis. Patients receiving this antibody become lymphopenic and may also become neutropenic, anemic, and thrombocytopenic. As a result patients should be closely monitored for opportunistic infections and hematologic toxicity. 

Chlorambucil (Leukeran) is the least toxic nitrogen mustard, and is used as the drug of choice in the treatment of chronic lymphocytic leukemia. It is absorbed orally, is slow in its onset of action, and may cause bone marrow depression. 

Fludarabine phosphate (2-fluoro-arabinofuranosyladenine monophosphate) is rapidly dephosphorylated to 2-fluoro-arabinofuranosyladenine and then phosphorylated intracellularly by deoxycytidine kinase to the triphosphate. This metabolite interferes with DNA synthesis through inhibition of DNA polymerase- and ribonucleotide reductase, and it also induces apoptosis. Fludarabine phosphate is used chiefly in the treatment of low-grade non-Hodgkin s lymphoma and chronic lymphocytic leukemia (CLL). Fludarabine phosphate is given parentally and is excreted primarily in the urine its dose-limiting toxicity is myelosuppression. 

Patients with early-stage chronic lymphocytic leukemia (CLL) have a relatively good prognosis, and therapy has not changed the course of the disease. However, in the setting of high-risk disease or in the presence of disease-related symptoms, treatment is indicated. 

Melphalan is an antineoplastic drug, listed also as a Class I immunosuppressive agent (effective only when given prior to the immune stimulus) [1]. It is used for the treatment of multiple myeloma, ovarian carcinoma, tumors of the testes, chronic granulocytic leukemia, chronic lymphocytic leukemia, seminoma, Ewing s sarcoma, reticulum cell sarcoma, and thymoma [1,2]. Its use as an adjuvant to surgery in the management of primary breast cancer was one of the first illustrations of the therapeutic potential of combined modalities of treatment [3]. 

Osterborg, A., Dyer, M. J., Bunjes, D., Pangalis, G. A., Bastion, Y., Catovsky, D., and Mellstedt, H. (1997). Phase II multicenter study of human CD52 antibody in previously treated chronic lymphocytic leukemia. European Study Group of CAMPATH-IH Treatment in Chronic Lymphocytic Leukemia./. Clin. Oncol. 15, 1567-1574. 

Winkler U, Jensen M, Manzke O, Schulz H, Diehl V, Engert A. Cytokine-release syndrome in patients with B-cell chronic lymphocytic leukemia and high lymphocyte counts after treatment with an anti-CD20 monoclonal antibody (rituximab, IDEC-C2B8). Blood 1999 94(7) 2217-24. 

Alemtuzumab (campath-lH) is a humanized monoclonal antibody specific for the CDw52 antigen, present on cell membranes of lymphocytes and monocytes. It has been used for treatment of patients with rheumatoid arthritis and vasculitis, is being investigated for the treatment of chronic lymphocytic leukemia, and has been used to deplete circulating lymphocytes in patients with multiple sclerosis (1). In 2001, alemtuzumab was approved in Europe for the treatment of chronic B cell lymphocytic leukemia that had been treated previously with alkylating agents and was refractory to fludarabine (2). It has also been used for induction of immunosuppression/tolerance in liver transplant recipients (3,4) and kidney/pancreas transplant recipients (5). 

Reactivation of cytomegalovirus is a frequent complication during treatment with alemtuzumab in patients with chronic lymphocytic leukemia (10), and other organisms are occasionally described. 

Among 18 patients with chronic lymphocytic leukemia, one with a long-lasting lymphocytopenia died 3 months after treatment, owing to progressive multifocal leuko-encephalopathy papovavirus was isolated from the cerebrospinal fluid (12). 

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