Chronic lymphocytic leukaemia

Keywords: CLL

Diagnosis

Appropriate Tests

CLL is a chronic lymphoproliferative disorder.

It is the most common leukaemia in Western countries, and is essentially a disease of the elderly, though it is not unusual to diagnose CLL in a younger patient.

Full blood count – in early stages of the disease, there is a mature lymphocytosis with smear cells without perturbation of other cell lineages. Cytopenias may develop in later stages with progressive bone marrow infiltration.

Blood film may occasionally show cytopenias due to immune destruction (eg, haemolysis, immune thrombocytopenia), or if splenomegaly is present (from splenic sequestration).

Flow cytometry on lymphocytes shows a typical immunophenotype (CD5/19 coexpressing cells with CD23 positivity and weak light chain restriction).

Bone marrow aspiration and trephine biopsy are not always required if a definite diagnosis is available on immunophenotyping. However, may be indicated when therapy for CLL is to be commenced to assess tumour burden and for prognostic cytogenetic studies.

Immunoglobulins levels of IgG, A, M; Protein electrophoresis - serum with immunofixation to detect a paraprotein.

See Table 2.

Immunoglobin heavy chain mutation status or Zap-70 assessment have been shown to correlate with clinical outcome, however, tests such as ZAP-70 are not readily available at all laboratories, and are not standardised across laboratories..

Beta-2-microglobulin and Lactate dehydrogenase in serum.

Lymph node biopsy is rarely indicated.

See Table 1.

See also Lymphoproliferative disorders and Chronic leukaemia

Complications:

 
  • Infections – due to dysfunctional immune system (hypogammaglobulinaemia, cell-mediated immunity, complement defects and innate immunity), and current/prior therapy (eg, chlorambucil, fludarabine, rituximab and alemtuzumab)

See Humoral immune deficiency under Infection (increased susceptibility).

See Cell mediated (T cell) immune dysfunction under Infection (increased susceptibility).

  • Anaemia

Full blood count and film, Reticulocyte count, haemolytic screen (Lactate dehydrogenase, Bilirubin, Haptoglobin, Direct antiglobulin test) for assessment of haemolysis and regenerative capacity of erythroid precursors.

  • Autoimmune haemolytic anaemia
 
  • Marrow infiltration (advanced disease)

Bone marrow biopsy may be required to assess tumour burden and degree of marrow infiltration.

  • Pure red cell aplasia (PRCA)
 
  • Thrombocytopenia
 
  • Immune thrombocytopenia
 
  • Hyperspl​enism
 
  • Marrow infiltration
 
  • Secondary cancers
 
  • Haematological (eg, transformation of CLL to large cell lymphoma, ie, Richter’s transformation, or prolymphocytic leukaemia; therapy related myelodysplastic syndrome or AML)

Richter’s transformation may require biopsy (Lymph node biopsy, Bone marrow biopsy) and correlation with other biochemical markers of tumour burden, eg, LDH, beta-2-microglobulin.

  • Solid organ malignancies
 
  • Leucostasis (rare unless lymphocyte counts > 400 x 109/L)
 
  • Tumour lysis syndrome with therapy (hyperphosphataemia, hypocalcaemia, hyperuricaemia, renal dysfunction)

Urea, Electrolytes, Calcium, Magnesium, Phosphate, Uric acid levels.

ECG for assessment of cardiac rhythm with electrolyte imbalance.