Diagnosis of chronic lymphocytic leukaemia generally involves full blood counts, differential counts, a blood smear and immunophenotyping. Investigations of patients at diagnosis should include Eichhorst et al., 2015; Hallek et al., 2008; Hallek, 2017; Oscier et al., 2012):

  • Full blood count and differential count to determine: white blood cell count, haemoglobin and haematocrit, platelet count, percent and absolute number of lymphocytes and reticulocytes. If prolymphocytes are present, assessing the proportion of these is also preferable.
  • Serum biochemistry including LDH, direct antiglobulin test (DAT) and serum immunoglobulins: it may also be useful to measure serum markers such as CD23, thymidine kinase and β2-microglobulin which may be associated with  survival or progression free survival.
  • Immunophenotype to distinguish CLL from other lymphoproliferative disorders as described in differential diagnosis.

Additional pre-treatment tests include (Eichhorst et al., 2015; Hallek, 2017; Oscier et al., 2012):

  • Detection of genetic abnormalities (especially deletions 17p and 11q or TP53 mutations) by fluorescent in situ hybridisation (FISH) as such mutations have therapeutic implications. UK guidelines do not currently recommend screening for such markers in patients with early stage CLL who do not have a clinical indication for treatment.
  • Infection status (e.g. hepatitis B & C, human immunodeficiency virus [HIV], cytomegalovirus [CMV]) especially prior to chemoimmunotherapy, alemtuzumab or allogeneic stem cell transplant.
  • Bone marrow biopsy is not required for the diagnosis of CLL, but is mandatory to define complete response. Bone marrow biopsy is strongly recommended prior to starting myelosuppressive therapy and for diagnostic evaluation of cytopenias both pre- and post-treatment.
  • Lymph node biopsy is indicated when there is diagnostic uncertainty or clinical suspicion of lymphomatous transformation. In the case of transformation which may be localised, CT/PET scanning may be useful in determining the most relevant site to biopsy.
  • CT scanning is often mandatory in patients entered into clinical trials.
  • CT scanning is indicated if there is clinical concern regarding possible thoracic, abdominal or pelvic nodal disease, or disease transformation.
  • Pre- and post-treatment CT scanning should be considered for patients treated with more intensive therapies.