Chronic lymphocytic leukaemia

Mabcampath (EU) or Campath (USA) alemtuzumab a humanized monoclonal antibody directed against CD52 surface antigen of B-lymphocytes) Millennium ILEX (EU) Berlex, ILEX Oncology Millennium Pharmaceuticals (USA) Chronic lymphocytic leukaemia... 

Pastor-Anglada, M., Molina-Arcas, M., Casado, F.J., Bellosillo, B., Colomer, D. and Gil, J. (2004) Nucleoside transporters in chronic lymphocytic leukaemia. Leukemia, 18, 385-393. 

Alemtuzumab Chronic lymphocytic leukaemia, multiple sclerosis... 

Plosker GL. Rituximab. A review of its use in non-Hodgkin s lymphoma and chronic lymphocytic leukaemia. Drugs 2003 63 803 3. 

Ghia P, Chiorazzi N, Stamatopoulos K (2008) Microenvironmental influences in chronic lymphocytic leukaemia the role of antigen stimulation. I Intern Med 264 549-562... 

Buggins AG, Pepper Cl (2010) The role of Bcl-2 family proteins in chronic lymphocytic leukaemia. Leuk Res 34 837-842... 

Willimott S, Baou M, Naresh K et al (2007) CD154 induces a switch in pro-survival Bcl-2 family members in chronic lymphocytic leukaemia. Br J Haematol 138 721-732... 

Pepper C, Mahdi JG, Buggins AG et al (2011) Two novel aspirin analogues show selective cytotoxicity in primary chronic lymphocytic leukaemia cells that is associated with dual inhibition of Rel A and COX-2. Cell Prolif 44 380-390... 

McCaig AM, Cosimo E, Leach MT et al (2011) Dasatinib inhibits B cell receptor signalling in chronic lymphocytic leukaemia but novel combination approaches are required to overcome additional pro-survival microenvironmental signals. Br J Haematol 153(2) 199-211... 

This outline is not exhaustive. For example there is an increasing awareness of the role played by infection with the human immunodeficiency virus while infiltration of the marrow with fibrous tissue or tumour cells will decrease production. In much the same way massive splenomegaly, so common in tropical Africa, sequesters significant volumes of red cells while malarial infection results in their accelerated breakdown. In some cases defects are multifactorial as in chronic lymphocytic leukaemia where infiltration decreases production, splenomegaly traps large amounts of blood while immune mechanisms lead to shortened survival or haemolysis. 

Physiologically, these plasma changes are included here since they reflect impaired numbers or function of B-lymphocytes. Two broad categories are recognizable. First, such immunodeficiency states may exist on congenital basis and often do so with concurrent defects in the T cells (Fig. 1). Alternatively, severe reductions in immunoglobulin levels often develop in the course of chronic lymphocytic leukaemia and myeloma. Not dissimilar impairment of immune competence is found with nephrotic syndrome, protein-losing enteropathy or even malnutrition, and in these instances is equally profound. 

Management may on occasions have to be splenectomy but in these situations there are generally other factors. For example, in chronic lymphocytic leukaemia contributions to the thrombocytopenia that occurs from reduced production of the one hand and rapid clearance due to immune mechanisms on the other. 

Fludarabine (Fludara ) is a 2-fluorocytarabine (Figure 8.5) that inhibits DNA biosynthesis via inhibition of DNA polymerase a and of RNDR. It is used clinically for the treatment of leukemia (chronic lymphocytic leukaemia—CLL). 

It is indicated in chronic lymphocytic leukaemia (drug of choice), primary... 

It is indicated in acute myelocytic leukaemia, acute lymphocytic leukaemia, chronic myeloid leukaemia (blast phase), non-Hodgkin s lymphoma in children, treatment and maintenance of meningeal neoplasms, erythroleukaemia. 

Four population-based case-control studies have examined associations of carbon tetrachloride with chronic lymphocytic leukaemia, brain cancer, female breast cancer and intraocular melanoma. Findings were generally unremarkable. In a fifth case-control study, which examined several cancers, no association was found with non-Hodgkin lymphoma, although the power to detect an increased risk was low. 

D27. Durig, J., Naschar, M., Schmucker, U., Renzing-Kohler, K., Holter, T., Huttmann, A., and Duhrsen, U., CD38 expression is an important prognostic marker in chronic lymphocytic leukaemia. Leukemia 16, 30-35 (2002). 

Osterborg, A., Fassas, A. S., Anagnostopoulos, A., Dyer, M. J., Catovsky, D., and Mellstedt, H. (1996). Humanized CD52 monoclonal antibody Campath-IH as first-line treatment in chronic lymphocytic leukaemia. Br. J. Haematol. 93, 151-153. 

Alvocidib (flavopiridol, HMR 1275) 66 (Sanofi-Aventis) is being evaluated in Phase II/III trials for the treatment of chronic lymphocytic leukaemia in collaboration with Ohio State University and the US National Cancer Institute (NCI).124 Alvocidib 66 is also being evaluated in Phase I and II trials against... 

Chronic lymphocytic leukaemia (CLL) Chronic myelogenous leukaemia (CML) Chlorambucil i prednisolone Fludarabinc... 

Otton SH, Turner DL, Frewin R, Davies SV, Johnson SA. Autoimmune thrombocytopenia after treatment with Campath IH in a patient with chronic lymphocytic leukaemia. Br J Haematol 1999 106(l) 261-2. 

Alendronate therapy of a patient with chronic lymphocytic leukaemia has been associated with the onset of acufe granulomatous interstitial nephritis, a relatively rare renal pathology primarily caused by adverse drug reactions [27]. In this case, treatment with oral alendronate was initiated 2 weeks before... 

NSC 312887 Fludara ) is a nucleotide antimetabolite ANTICANCER AGENT, used to treat leukaemia (chronic B-cell lymphocytic leukaemia, CLL). 

Torres-Garcia, S. J., Cousineau, L., Caplan, S., andPanasci, L. (1989) Correlation of resistance to nitrogen mustards in chronic lymphocytic leukaemia with enhanced removal of melphalan-induced DNA crosslinks. Biochem. Pharmacol. 38,3122-3123. 

Damle RN, Calissano C, Chiorazzi N (2010) Chronic lymphocytic leukaemia a disease of activated monoclonal B cells. Best Pract Res Clin Haematol 23 33-45... 

Silvennoinen R et al. Pharmacokinetics of chlorambucil in patients with chronic lymphocytic leukaemia comparison of different days, cycles and doses. Pharmacology Toxicology, 2000, 87 223-228. 

P3. Pitney, W. R., Joske, R. A., and Mackinnon, N. L., Folic acid and other absorption tests in lymphosarcoma, chronic lymphocytic leukaemia and some related conditions. J. Clin. Pathol. 13, 440-447 (1960). 

Co-operative Group for the Study of Immunoglobulin in Chronic Lymphocytic Leukaemia (1988). Intravenous immunoglobulin for the prevention of infection in chronic lymphocytic leukaemia. N Eng J Med, 6, 902-907. 

Fong D, Kaiser A, Spizzo G, et al. Hodgkin s disease variant of Richter s syndrome in chronic lymphocytic leukaemia patients previously treated with fludarabine. Br J Haematol. 2005 129 199-205. 

Aguilar-Santelises M, Magnusson KP, Wiman KG, et al. Progressive B-cell chronic lymphocytic leukaemia frequently exhibits aberrant p53 expression. Int J Cancer. 1994 58(4) 474-479. 

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