Chronic lymphocytic leukemia: 2013 update on diagnosis, risk stratification and treatment

Am J Hematol. 2013 Sep;88(9):803-16. doi: 10.1002/ajh.23491.

Abstract

Disease overview: 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.

Diagnosis: 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.

Prognosis: 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 most available therapies.

Therapy: 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 represents the current standard therapy. For unfit patients, treatment with an anti-CD20 antibody plus a milder chemotherapy (chlorambucil) is currently established as standard treatment. At relapse, the initial treatment may be repeated, if the treatment-free interval exceeds two years. If the disease relapses earlier, alternative therapies such as bendamustine alone or with rituximab, alemtuzumab, lenalidomide, or ofatumumab should be used. Patients with a del(17p) or TP53 should be considered for an allogeneic SCT.

Future challenges: Several new agents (e.g., ibrutinib, obinutuzumab) hold the potential to change standard of CLL treatment in the next 6-12 months. Therefore, CLL patients should be included into current clinical trials whenever possible.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / pathology
  • Blood Cell Count
  • CD5 Antigens / genetics
  • CD5 Antigens / metabolism
  • Chromosomes, Human, Pair 17
  • Gene Expression
  • Humans
  • Leukemia, Lymphocytic, Chronic, B-Cell / classification
  • Leukemia, Lymphocytic, Chronic, B-Cell / diagnosis
  • Leukemia, Lymphocytic, Chronic, B-Cell / pathology
  • Leukemia, Lymphocytic, Chronic, B-Cell / therapy*
  • Risk Factors
  • Sequence Deletion
  • Stem Cell Transplantation*
  • Transplantation, Homologous
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • CD5 Antigens