Indications for Treatment

Patients with asymptomatic, early stage CLL (Binet stage A, Rai stage 0) should be monitored every 3–12 months (blood cell counts and clinical examination) without treatment, i.e. employing a 'watch and wait' strategy, unless there is evidence of progressive disease (Eichhorst et al., 2015; Hallek, 2017; Stilgenbauer et al., 2015).

Treatment should only be given to patients with active, symptomatic disease (as follows) (Hallek et al., 2017, Eichhorst et al., 2017; Oscier et al., 2012; Stilgenbauer et al., 2015):

  • Evidence of progressive marrow failure (anaemia and/or thrombocytopenia)
  • Massive (i.e. ≥6 cm below the left costal margin) or progressive or symptomatic splenomegaly
  • Massive nodes (i.e. ≥10 cm in longest diameter) or progressive or symptomatic lymphadenopathy
  • Progressive lymphocytosis with an increase of >50% over a 2-month period
  • Lymphocyte doubling time (LDT) of <6 months
  • Autoimmune anaemia and/or thrombocytopenia that is poorly responsive to corticosteroids or other standard therapy
  • Disease-related symptoms such as unintentional weight loss ≥10% within the previous 6 months, significant fatigue, fevers of greater than 38.0 oC for 2 or more weeks without other evidence of infection; or night sweats for more than 1 month without evidence of infection.

Active symptomatic disease, as defined in guidelines published by the International Workshop on Chronic Lymphocytic Leukaemia (IWCLL), relates to patients with intermediate risk Rai stage I and II, and high risk Rai stage III and IV disease, or Binet stage B or C disease. However, some patients with Rai intermediate risk/Binet stage B disease can be monitored without therapy until they have progressive, symptomatic or active disease (Hallek, 2017; Hallek et al., 2008).

The timing of treatment, especially in asymptomatic patients, depends partly on the rate of disease progression. Treatment should not be delayed to the point at which it may be less effective and/or more difficult to administer (e.g. due to cytopenias) especially in patients with high risk CLL (Oscier et al., 2012).