What is the treatment approach for lymphocytosis?

Treatment Approach for Lymphocytosis

The treatment of lymphocytosis should not be initiated based solely on an elevated lymphocyte count but requires evidence of active disease progression according to established criteria from international guidelines. 1, 2

Diagnostic Evaluation

Before considering treatment, a thorough diagnostic workup is essential:

• Confirm the diagnosis with:
  • Peripheral blood immunophenotyping (CD5+, CD23+, CD20 dim+, sIg dim+) 2
  • Bone marrow evaluation if clinically indicated
  • FISH analysis for cytogenetic abnormalities (del(17p), del(11q), del(13q), trisomy 12) 2, 1
  • IGHV mutation status assessment 1

Treatment Indications

Treatment should only be initiated when at least one of these criteria is met:

• Progressive marrow failure (worsening anemia with Hb <100 g/L or thrombocytopenia <100×10⁹/L) 2
• Massive (≥6 cm below left costal margin) or symptomatic splenomegaly 2
• Massive (≥10 cm diameter) or symptomatic lymphadenopathy 2
• Progressive lymphocytosis with ≥50% increase over 2 months or lymphocyte doubling time <6 months 2, 1
• Autoimmune complications poorly responsive to corticosteroids 2
• Symptomatic extranodal involvement 2
• Constitutional symptoms (weight loss >10% in 6 months, significant fatigue, fever >38°C for ≥2 weeks without infection, night sweats) 2

Treatment Algorithm

Step 1: Risk Stratification

• Determine genetic profile (del(17p), TP53 mutations, IGHV status) 1
• Assess patient fitness and comorbidities 1

Step 2: Treatment Selection Based on Risk Profile

For patients with del(17p) or TP53 mutations:

• BTK inhibitors (ibrutinib, acalabrutinib, or zanubrutinib) as first-line therapy 1

For patients without del(17p) or TP53 mutations:

• Young/fit patients with mutated IGHV: FCR (fludarabine, cyclophosphamide, rituximab) as time-limited therapy 2, 1
• Young/fit patients with unmutated IGHV: BTK inhibitor therapy or venetoclax + obinutuzumab 2, 1
• Older/less fit patients: Chlorambucil + obinutuzumab, BTK inhibitor, or venetoclax + obinutuzumab 2

Early Disease Management

For patients with early-stage disease (Binet stage A/B without symptoms or Rai 0-II without symptoms):

• Implement a "watch and wait" strategy with blood count monitoring every 3 months 2
• Monitor for disease progression indicators 2

Common Pitfalls to Avoid

• Do not treat based solely on absolute lymphocyte count - this can lead to unnecessary treatment 1
• Do not overlook autoimmune cytopenias - these may require specific interventions different from CLL treatment 1
• Do not fail to distinguish between stable and progressive lymphocytosis - stable disease may not require intervention 1
• Do not neglect assessment for Richter's transformation - particularly in patients with rapid clinical deterioration 1

Monitoring During Treatment

• Regular clinical examinations and blood counts 2
• Evaluation of treatment response using standardized criteria 2
• Assessment for minimal residual disease when appropriate 2
• Vigilance for infectious complications, which are common in CLL patients 3

By following this structured approach to lymphocytosis management, clinicians can ensure appropriate treatment timing and selection, ultimately improving patient outcomes in terms of morbidity, mortality, and quality of life.