Chapter 33

In chronic lymphocytic leukaemia:

  • FLCs are the most commonly detected monoclonal proteins, with an abnormal sFLC ratio present in 30 - 40% of patients at diagnosis.
  • Elevated polyclonal FLCs are present in a further 15% of patients at diagnosis.
  • A monoclonal or polyclonal FLC elevation is associated with a shorter time to first treatment and reduced overall survival.
  • Summated κ + λ FLCs is an important new prognostic marker that identifies patients requiring early treatment.

With an incidence of 4.2 per 100,000 per year, chronic lymphocytic leukaemia (CLL) is the most common type of leukaemia in the Western world [726] The median age at presentation is 72 years and the incidence is higher in men than women [726]. CLL is a clinically heterogeneous disease. Approximately two-thirds of patients are asymptomatic at diagnosis, and CLL is frequently diagnosed incidentally, following a routine full blood count. Other patients present with lymphadenopathy, systemic symptoms (such as tiredness, night sweats and weight loss), or infection. The clinical outcome of CLL is variable. Some patients survive for decades without requiring treatment, whilst others experience an aggressive form of the disease and may die shortly after diagnosis, either of disease- or therapy-related complications [726].

The diagnosis of CLL is based on the presence of an absolute monoclonal B-cell count of >5 x 109/L in the peripheral blood (persisting for >3 months) with a characteristic immunophenotype and morphology [727]. Two related disorders—monoclonal B-cell lymphocytosis (MBL) and small lymphocytic lymphoma (SLL) —share many clinical and diagnostic features in common with CLL. A diagnosis of MBL requires a monoclonal B-cell count of <5 x 109/L, in the absence of lymphadenopathy or organomegaly, cytopenias or disease-related symptoms [727]. SLL is also characterised by a B-cell count of <5 x 109/L, with the addition of lymph node or other tissue infiltration by cells characteristic of CLL [727].

Two well-established CLL clinical staging systems (Rai and Binet) are in routine use. These are particularly useful for predicting outcome in patients presenting with lymphadenopathy, hepatosplenomegaly or bone marrow failure [726]. However, significant clinical heterogeneity exists within patients classified as early CLL (Binet stage A or Rai stage 0/1). Therefore, additional prognostic markers are required to identify patients at risk of clinical progression. A number of prognostic biomarkers have been shown to predict progression and survival in CLL. These include immunoglobulin heavy chain variable region gene (IGHV) mutation status, serum β2-microglobulin, CD38/ZAP-70 expression, and cytogenetic abnormalities [728]. However, these techniques have several limitations. For example, assessment of IGHV mutation status is complex, expensive and is not widely available. Other techniques (e.g. ZAP-70 expression) are poorly standardised and suffer from significant inter-laboratory variation [729].