Overview

Chronic lymphocytic leukaemia (CLL) is a cancer of the bone marrow leading to the production of lymphocytes accumulating in the blood, bone marrow, spleen, liver, and lymph nodes. These cells appear normal but are immature and non-reactive (they do not function) and crowd out normal blood cells. CLL typically worsens gradually over the years.

The cells in CLL are nearly always B-cells.

Epidemiology

  • The median age of diagnosis is 72 years
  • Usually seen in adults >55 years

Risk Factors

  • >55 years of age
  • Family history

Example History

A 75-year-old man has had lethargy for the past 4 weeks. He denies fevers, chills, weight loss, or night sweats.

Investigations:

Haemoglobin:125 g/L(130 – 180 g/L)
Platelets:153 x 109/L(150 – 450 x 109/L)
Mean cell volume (MCV):80.0 fL(76.0 – 98.0 fL)
White blood cells (WBC):20.0 x 109/L(3.0 – 10.0 x 109/L)
Neutrophils:3.5 x 109/L(2.00 – 7.00 x 109/L)
Lymphocytes:15.3 x 109/L(1.00 – 4.00 x 109/L)
Monocytes:0.30 x 109/L(0.20 – 0.80 x 109/L)
Eosinophils:0.00 x 109/L(0.00 – 0.40 x 109/L)
Basophils:0.00 x 109/L(0.00 – 0.20 x 109/L)
Blood film:Smudge cells seen

Presentation

Patients are often asymptomatic and CLL may be picked up incidentally with routine tests showing increased numbers of lymphocytes. Other features are:

  • Features of anaemia:
  • Lymphadenopathy:
    • If CLL cells infiltrate the lymph nodes
  • Splenomegaly:
    • Due to increased sequestration of abnormal cells
  • Constitutional symptoms – fevers, chills, night sweats, weight loss, fatigue
  • Recurrent and severe infections – due to dysfunctional lymphocytes
  • Petechiae – due to thrombocytopenia which may develop due to bone marrow crowding

Differential Diagnoses

Acute lymphoblastic leukaemia (ALL)

  • Usually seen in children <5 years
  • Patients typically have anaemia, neutropenia, and thrombocytopenia
  • Blood film shows blast cells but not cells at different stages of maturation

Chronic myeloid leukaemia (CML)

  • In CLL patients are usually asymptomatic, but in CML they may have anaemia, weight loss, and night sweats
  • CML generally causes profound splenomegaly that may be large enough to cause abdominal discomfort
  • Blood film shows myeloid cells (e.g. granulocytes) at different stages of maturation and thrombocytosis unlike in CLL which shows smudge/smear cells

Investigations

Overview

  • FBC and white cell differential:
    • Haemoglobin: may be normal/low
    • White blood cells: elevated
    • Lymphocytes: elevated
    • Platelets: may be low/normal
  • Blood film:
    • Shows smudge/smear cells – these are lymphocytes that are damaged during slide preparation
    • Spherocytes may be seen if there is haemolysis
  • Flow cytometry – most important for confirming CLL:
    • Analyses cells using flow cytometry looking for antigens specific for CLL
    • May be positive for CD5, CD19, CD20, CD23

Management

Overview

Treatment is performed on a case-by-case basis and guided by an oncology multidisciplinary team. Chemotherapy, radiotherapy, surgery, and stem cell transplantation are often used.

Complications

  • Increased susceptibility to infection
  • More severe infection
  • Warm-type autoimmune haemolytic anaemia
  • Richter’s syndrome – transformation of CLL to a high-grade lymphoma 
    • Patients become suddenly very unwell with lymphadenopathy and constitutional symptoms

Prognosis

  • Median survival from diagnosis is between 18 months to >10 years depending on what stage of CLL the patient has
  • Patients with a mutation of the p53 gene or 17p deletion have the poorest prognosis

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