Treatment

Indications for anticancer therapy: based on disease risk (Rai staging) and disease activity

• Low-risk disease (Rai stage 0)

  • Expectant management

• Intermediate risk disease (Rai stage I or II)

  • Consider expectant management if stable and asymptomatic.

  • Medical therapy: indicated for progressive or symptomatic disease (i.e., active disease)

• High-risk disease (Rai stage III or IV): medical therapy

Anticancer therapy may include:

• Targeted therapy, e.g., ibrutinib, rituximab, alemtuzumab

• Chemoimmunotherapy, e.g., FCR: fludarabine, cyclophosphamide, rituximab

• Allogeneic HSCT: currently the only curative treatment option (not routinely performed)

Immunosuppression with subsequent infections (most common cause of death)

Secondary malignancies

Hyperviscosity syndrome

Autoimmune hemolytic anemia (of both the warm and cold agglutinin type)

Richter transformation or Richter syndrome: transformation into a high-grade NHL (usually diffuse large B cell lymphoma)

• Occurrence: ∼ 5% of cases

• Diagnostic indicators:

  • Rapidly progressive lymphadenopathy → lymph node biopsy required

  • New onset of B symptoms

  • ↑ LDH

• Treatment: similar to symptomatic CLL and advanced stages

Older age is associated with a poor overall survival rate.

Rai staging

Adverse prognostic markers in CLL, e.g.:

• Del(17p13)

• Elevated β2-microglobulin level

Blood lymphocyte doubling time: Rapid doubling is associated with a high risk of disease progression.