Chronic lymphocytic Leukemia

 

• Background

  

  
  

  Pathophysiology

  • Proliferation of mature B-cells.
  • Differs from lymphoma in that the accumulation is mainly in blood and bone marrow, though lymph nodes can be affected.

  Epidemiology

  • Commonest adult leukaemia. 1/5000 annual incidence >65 years, and 1/3000 >80 years.
  • Commoner in males.

• Presentation

  90% are asymptomatic at presentation, with an incidentally detected ↑WBC. On examination, findings include lymphadenopathy (50%), splenomegaly (30%), and hepatomegaly (15%).

  Symptomatic disease includes:

  • Cytopaenia from bone marrow infiltration or autoimmunity: anaemia (SOB, fatigue), thrombocytopaenia (petechiae).
  • Systemic symptoms: weight loss, sweats, anorexia.
  • Recurrent infection due to dysfunctional lymphocytes causing ↓immunoglobulins: pneumonia, VZV.

• Investigations

  FBC:

  • ↑WBC, with lymphocytes >5000/μl and sometimes much higher. Must persist for >3 months to make diagnosis.
  • ↓Platelets (15%)
  • Anaemia: due to bone marrow failure or DAT +ve haemolytic anaemia.

  Other bloods:

  • DAT test if anaemic.
  • Blood film: lymphocytosis, smudge cells (lymphocytes damaged in slide preparation).
  • Immunophenotyping with peripheral flow cytometry: CD5, CD19, CD20, CD23.
  • Immunoglobulins if recurrent infection.

  Biopsy:

  • Lymph node biopsy if enlarged.
  • Bone marrow biopsy and aspirate are optional.

  Staging:

  • Binet system (A-C) is based on bloods (WBC, Hb) and clinical findings (lymphadenopathy).
  • CT not usually needed.

• Management

  Watchful waiting:

  • For asymptomatic disease (Binet A-B).
  • 3-monthly FBC, flow cytometry, and examination.

  Chemotherapy:

  • For active, symptomatic disease (Binet C).
  • Common regimens include FCR (Fludaribine, Cyclophosphamide, Rituximab) or newer agents such as the Bruton tyrosine kinase inhibitor ibrutinib.
  • Up to 50% remission, but most relapse.

  Stem cell transplantation:

  • For refractory disease.

• Complications and prognosis

  Complications:

  • Recurrent infection from treatment or disease.
  • Richter transformation to high-grade Non-Hodgkin's lymphoma.
  • Hyperviscosity syndrome.

  Prognosis:

  • Binet A: median survival of over 10 years, and is unlikely to markedly limit life expectancy.
  • Binet C: median survival 2-3 years.