Chronic Lymphocytic Leukaemia

Abstract

Chronic lymphocytic leukaemia (CLL) results from the expansion of a clone of CD5+ B lymphocytes with distinct morphology and membrane antigens. The clinical course is variable and is determined by the stage of the disease. A number of serum, immunological and genetic markers are important determinants of prognosis. Treatment is only indicated in symptomatic patients with active disease. Initial therapy for fit patients is usually with combination chemoimmunotherapy, whereas single alkylating agents continue to be used for those unable to tolerate more intensive treatments. The presence of TP53 deletion, detected by fluorescence in situ hybridisation (FISH) analysis, predicts for poor response to conventional treatments and should be assessed in all patients before initiating therapy so that an alternative regimen can be selected. A number of new agents have shown activity in CLL.

Key Concepts:

  • CLL results from an expansion of clonal CD5+ CD19+ Blymphocytes with a unique diagnostic immunophenotype.

  • The clinical course of CLL is highly variable with some patients surviving decades without treatment, whereas others may die within 3–5 years of diagnosis.

  • Clinical stage and new laboratory markers give prognostic information. Patients whose CLL cells harbour TP53 deletions or mutations have a particularly poor outcome.

  • Patients with early stage asymptomatic disease do not require treatment.

  • Combination chemoimmunotherapy is recommended for fit patients with no TP53 abnormality.

  • Single agent alkylator therapy (chlorambucil or bendamustine) is suitable for less fit patients.

  • A number of newer agents are now available for management of relapsed/refractory patients.

  • Where possible patients should be treated within a clinical trial.

  • Allogeneic transplantation should be considered for younger fit patients with high‐risk disease.

  • Care in the prevention and management of infections is crucial.

Keywords: B lymphocytes; lymphocytic leukaemia; lymphocytosis; lymphoma; prolymphocytes; splenectomy; clinical stage; doubling time; FISH

Figure 1.

Blood film from a patient with chronic lymphocytic leukaemia, showing typical small lymphocytes.

Figure 2.

Blood film from a patient with chronic lymphocytic leukaemia with more than 10% prolymphocytes (CLL‐PL), showing the coexistence of four small lymphocytes and four prolymphocytes (larger and nucleolated).

Figure 3.

FISH analysis with a centromeric probe for chromosome 12 showing three green dots (trisomy 12) in all the cells, and with a probe for 13q14 (two red dots) showing deletion (one red dot) in most cells with trisomy 12.

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Further Reading

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Swerdlow SH, Campo E and Harris NL et al. (eds) (2008) WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues, vol. 2, 127 pp. Lyon: IARC.

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Dearden, Claire(Jan 2013) Chronic Lymphocytic Leukaemia. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0002173.pub3]