title: Chronic lymphocytic leukemia: 2015 Update on diagnosis, risk stratification, and treatment.
abstract: BACKGROUND
  Chronic lymphocytic leukemia (CLL) is the commonest leukemia in western countries. 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.
  
  
  METHODS
  The diagnosis is established by blood counts, blood smears, and immunophenotyping of circulating B-lymphocytes, which identify a clonal B-cell population carrying the CD5 antigen as well as B-cell markers.
  
  
  CONCLUSIONS
  Two prognostic staging systems exist, the Rai and Binet staging systems, which are established by physical examination and blood counts. Various biological and genetic markers also have prognostic value. Deletions of the short arm of chromosome 17 (del(17p)) predict resistance to available chemotherapies. Comprehensive prognostic scores are currently being developed.
  
  
  METHODS
  Patients with active or symptomatic disease or with advanced Binet or Rai stages require therapy. For physical fit patients, chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab remains the current standard therapy. For unfit patients, treatment with an anti-CD20 antibody (obinutuzumab or rituximab or ofatumumab) plus a milder chemotherapy (Chlorambucil) may be applied. At relapse, the initial treatment may be repeated, if the treatment-free interval exceeds two to three years. If the disease relapses earlier, therapy should be changed using alternative agents such as bendamustine (plus rituximab), alemtuzumab, lenalidomide, ofatumumab, ibrutinib, or idelalisib. Patients with a del(17p) or TP53 mutation can be treated with ibrutinib or a combination of idelalisib and rituximab. An allogeneic SCT may be considered in relapsing patients with TP53 mutations or del(17p) or patients that are refractory to repeated chemoimmunotherapies. Future challenges: Several new agents (e.g., ibrutinib, idelalisib, obinutuzumab) hold the potential to improve the outcome of patients with CLL. However, their optimal use (in terms of combination, sequence, and duration) is unknown. Therefore, CLL patients should be treated in clinical trials whenever possible.
authors.affiliation: Department I of Internal Medicine, Center for Integrated Oncology Köln Bonn, Center of Excellence on "Cellular Stress Responses in Aging-Associated Diseases", University of Cologne, Cologne, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Hallek
mesh_terms: D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage; D018951:Antigens, CD20 / Q000235:genetics / Q000378:metabolism; D000971:Antineoplastic Combined Chemotherapy Protocols; D001402:B-Lymphocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D015415:Biomarkers / Q000378:metabolism; D018956:CD5 Antigens / Q000235:genetics / Q000378:metabolism; D002872:Chromosome Deletion; D002886:Chromosomes, Human, Pair 17; D002986:Clinical Trials as Topic; D003520:Cyclophosphamide / Q000008:administration & dosage; D015870:Gene Expression; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis* / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D000069283:Rituximab; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20; D015415:Biomarkers; D018956:CD5 Antigens; D000069283:Rituximab; D003520:Cyclophosphamide; D014740:Vidarabine; C024352:fludarabine