Update on diagnosis and treatment of Chronic Lymphocytic Leukemia (CLL)

Abstract

commonest leukemia found in adults western countries, affects more than 200000 people and is associated with approximately 4410 death in the USA annually. CLL is characterized by a progressive proliferation and accumulation of mature yet functionally incompetent lymphocytes. The disease typically occurs in elderly patients and has a highly variable clinical course. Leukemic transformation is initiated by specific genomic alterations that impair apoptosis of clonal B-cells. Diagnosis: The diagnosis of chronic lymphocytic leukemia (CLL) requires the presence of more than or equal to 5 × 109/L B lymphocytes (5000/μL) in the peripheral blood for the duration of at least 3 months. Immunophenotyping of circulating B-lymphocytes, which identify a clonal B-cell population carrying the CD5 antigen, as well as typical B-cell markers are confirmatory test. Prognosis: The two similar clinical staging systems, Binet and Rai stages, create prognostic information by using results of physical examination and blood counts. Various molecular biology markers also have prognostic value. Mutations of the TP53 gene and x chromosome 17 chromosome (del [17p) predict resistance to chemoimmunotherapy and a shorter time to progression, with most targeted therapies. A comprehensive, international prognostic score (CLL-IPI) integrates genetic, biological and clinical variables to identify distinct risk groups of CLL patients. Therapy: Early-stage disease of CLL patients are followed up regularly, only patients with active or symptomatic disease or with advanced stages of Binet or Rai require treatment. When treatment is indicated, most patients with CLL have several options: a combination of obinutuzumab and venetoclax, ibrutinib monotherapy, or immunochemotherapy. In patients under 65 years of age who are physically fit (particularly if they have a mutated IGVH gene), immunochemotherapy with fludarabine, cyclophosphamide, and rituximab remains the standard of care because of its potential therapeutic potential. In case of relapse, the initial treatment can be repeated if the treatment-free period exceeds 3 years. And in case of early recurrence of the disease, treatment should be switched to an alternative regime. Patients with del(17p) or TP53 mutations are another high-risk group and should be treated with targeted drugs. Allogeneic SCT can be considered in patients with TP53 or del(17p) mutations or in patients on inhibitor therapy.