What is the treatment for chronic lymphocytosis (Chronic Lymphocytosis)?

Treatment of Chronic Lymphocytosis

The standard treatment for chronic lymphocytosis (CLL) without symptoms is a "watch and wait" strategy with regular monitoring every 3 months, rather than immediate therapeutic intervention. 1

Diagnostic Clarification

Before discussing treatment, it's important to clarify that chronic lymphocytosis may refer to:

• Chronic Lymphocytic Leukemia (CLL): Defined by ≥5 × 10^9/L monoclonal B cells with characteristic immunophenotype
• Monoclonal B-cell Lymphocytosis (MBL): Similar phenotype to CLL but with <5 × 10^9/L B cells

Treatment Algorithm Based on Disease Stage and Symptoms

Asymptomatic Early-Stage Disease (Binet A/B, Rai 0-II without symptoms)

• First-line approach: Watch and wait with monitoring every 3 months 1
• Monitor: Complete blood count, physical examination of lymph nodes, liver, and spleen
• No survival benefit has been demonstrated with early intervention 1

Criteria for Initiating Treatment

Treatment is indicated when ANY of the following are present 1:

1. Progressive marrow failure (anemia, thrombocytopenia)
2. Massive/progressive/symptomatic splenomegaly (>6 cm below costal margin)
3. Massive/progressive/symptomatic lymphadenopathy (>10 cm diameter)
4. Progressive lymphocytosis with ≥50% increase over 2 months or lymphocyte doubling time <6 months
5. Autoimmune complications poorly responsive to corticosteroids
6. Symptomatic extranodal involvement
7. Disease-related symptoms (fatigue, night sweats, weight loss, fever)

Treatment Options for Symptomatic/Advanced Disease

For Physically Fit Patients (no major comorbidities)

• First-line options:
  • Bruton tyrosine kinase (BTK) inhibitors (ibrutinib, acalabrutinib, zanubrutinib) until progression 1
  • Venetoclax plus obinutuzumab (time-limited 12-month therapy) 1
  • FCR (fludarabine, cyclophosphamide, rituximab) for IGHV-mutated disease 1

For Patients with Significant Comorbidities

• First-line options:
  • Venetoclax plus obinutuzumab (preferred, time-limited therapy) 1
  • Chlorambucil plus obinutuzumab 1
  • Dose-reduced purine analog-based therapies 1
  • Bendamustine 1

For Patients with TP53 Mutation/del(17p)

• BTK inhibitors or venetoclax-based regimens (these patients respond poorly to conventional chemotherapy) 1

Treatment of Relapsed/Refractory Disease

• If relapse occurs >12-24 months after initial therapy: Consider repeating first-line treatment 1
• If relapse occurs <12-24 months or disease is refractory:
  • Switch to alternative therapy class (BTK inhibitor if previously on venetoclax or vice versa)
  • Consider alemtuzumab-containing regimens 1
  • For very high-risk disease: Consider allogeneic stem cell transplantation 1

Management of CLL Complications

• Autoimmune cytopenias: Corticosteroids as first-line; consider rituximab if steroid-resistant 1
• Infections: Consider antibiotic prophylaxis in high-risk patients; systemic immunoglobulin only for severe hypogammaglobulinemia with recurrent infections 1
• Vaccination: Recommend pneumococcal and seasonal influenza vaccines 1

Monitoring During Watch and Wait

• Complete blood count every 3 months
• Physical examination including lymph nodes, liver, and spleen
• Special attention to development of autoimmune cytopenias
• Monitor for secondary malignancies (2-7 fold increased risk) 1

Important Considerations

• B-cell count >11 × 10^9/L is a better predictor of treatment need than absolute lymphocyte count 2
• The diagnosis "leukemia" may cause unnecessary distress in patients who will never develop symptomatic disease 3
• Only about 1.1% of patients with MBL and lymphocytosis per year will progress to CLL requiring treatment 4
• Quality of life should be prioritized when making treatment decisions, particularly in elderly patients

Remember that CLL is generally an incurable disease, and the goal of therapy is to improve survival and quality of life while minimizing treatment-related toxicity.