Signs & Symptoms

Many patients with chronic lymphocytic leukaemia (CLL) are symptomatic. In up to 90% of cases CLL is diagnosed as an incidental finding during a routine blood test when elevated white blood cell and/or lymphocyte counts are seen. This section briefly summarises the signs and symptoms of CLL and outlines differential diagnosis.

Symptoms

Symptoms tend to worsen over time as the disease progresses and may include lymphadenopathy, tiredness, B symptoms (fever, night sweats and >10% weight loss in 6 months) or symptoms of anaemia or recurrent/persistent infections (CRUK, 2015; NICE, 2016; Nabhan & Rosen, 2014; Oscier et al., 2012). More rarely, patients may have bleeding or bruising or in the case of transformed CLL, bone pain and night sweats (CRUK, 2015).

Evaluation of a patient with possible symptoms of CLL should therefore be carried out to determine whether B symptoms (i.e. fever, weight loss, night sweats) and profound lethargy are CLL-related or have an alternative cause (Oscier et al., 2012).

Signs

In addition to the symptoms described, hepatosplenomegaly may be seen in 20–50% of patients at presentation (Nabhan & Rosen, 2014).

Laboratory abnormalities associated with chronic lymphocytic leukaemia (CLL) include (Nabhan & Rosen, 2014):

  • Absolute clonal B lymphocytosis, defined as greater than 5000 cells/μL.
  • Autoimmune haemolytic anaemia (AIHA) which may be seen in 1–11% of patients at diagnosis.
  • Autoimmune thrombocytopenia which may also be present at diagnosis but is seen in less than 2% of cases.
  • Elevated levels of low-density lipoprotein cholesterol and β2 microglobulin.
  • Hypogammaglobulinaemia which is present in 8–10% of patients at diagnosis.

Differential Diagnosis

Chronic lymphocytic leukaemia (CLL), small lymphocytic leukaemia (SLL) and monoclonal B cell lymphocytosis (MBL) share a common immunophenotype, lymphocyte morphology/histology, biological features, signs and symptoms. Key differences are outlined in Table 1. For further information please see the section on Diagnosis and Staging.

Table 1: Distinguishing between CLL, MBL and SLL (Oscier et al., 2012).
Criteria CLL MBL SLL

Clonal B lymphocytes > 5 x 109/L

Y

N

N

Disease-related cytopenias

Y/N

N

Y/N

B symptoms

Y/N

N

Y/N

Lymphadenopathy and/or splenomegaly

Y/N

N

Y

CLL, chronic lymphocytic leukaemia; MBL, monoclonal B cell lymphocytosis; SLL, small lymphocytic leukaemia; Y, yes; N, no.