What is the treatment for lymphocytosis (high lymphocytes)?

Management of Lymphocytosis

The management of lymphocytosis should follow a "watch and wait" approach unless specific criteria for active disease are met, as treatment is not indicated for asymptomatic elevated lymphocyte counts alone. 1

Diagnostic Evaluation

• Persistent lymphocytosis ≥5 × 10^9/L (5,000/μL) not explained by other disorders should prompt evaluation for Chronic Lymphocytic Leukemia (CLL) 2
• Initial evaluation should include:
  • Complete blood count with differential 1
  • Peripheral blood smear to identify characteristic lymphocyte morphology 2
  • Flow cytometry to determine immunophenotype (CD5+, CD19+, CD20+ low, CD23+) 2
  • Serum chemistry including LDH and immunoglobulin levels 1
  • Cytogenetic analysis (FISH) for del(17p) if CLL is suspected 1

Treatment Indications

Treatment is only indicated when there is evidence of active disease. The following criteria warrant intervention:

• Progressive marrow failure with anemia (Hb <100 g/L) or thrombocytopenia (platelets <100 × 10^9/L) 1
• Massive (>6 cm below costal margin) or symptomatic splenomegaly 1
• Massive (>10 cm diameter) or symptomatic lymphadenopathy 1
• Progressive lymphocytosis with >50% increase over 2 months or lymphocyte doubling time <6 months 1
• Autoimmune complications poorly responsive to corticosteroids 1
• Symptomatic extranodal involvement (skin, kidney, lung, spine) 1
• Disease-related symptoms (fatigue, night sweats, weight loss, fever) 1

Management Algorithm

1. Asymptomatic lymphocytosis without active disease:

   • Implement watch-and-wait strategy with monitoring every 3-12 months 1
   • Monitor blood counts and clinical examination for disease progression 1

2. For CLL with active disease requiring treatment:

   • Treatment selection based on:
     • TP53/del(17p) status 1
     • Patient age and comorbidities 1
     • Prior treatments (if relapsed disease) 1

3. First-line treatment options for CLL:

   • For fit patients: Bruton tyrosine kinase inhibitors (BTKi) like ibrutinib or chemoimmunotherapy with FCR (fludarabine, cyclophosphamide, rituximab) 1
   • For elderly/comorbid patients: Venetoclax plus obinutuzumab, chlorambucil plus obinutuzumab, or BTKi 1
   • For patients with del(17p)/TP53 mutations: Ibrutinib is preferred 1

4. For Adult T-cell Leukemia/Lymphoma (ATL) with lymphocytosis:

   • Chronic/smoldering ATL: AZT (1 g/day) and IFN-α (6-10 million units/day) 1
   • Acute ATL: AZT/IFN-α or chemotherapy (CHOP regimen) 1

5. For secondary Hemophagocytic Lymphohistiocytosis (HLH):

   • Combination of intravenous immunoglobulin and corticosteroids 3, 4
   • Identify and treat underlying infections or malignancies 4, 5

Special Considerations

• Lymphocytosis during BTKi therapy is expected and does not indicate treatment failure - continue treatment despite transient increase in lymphocyte count 1
• Autoimmune cytopenias in CLL patients typically respond to corticosteroids; consider splenectomy or monoclonal antibodies for refractory cases 1
• Prophylactic intravenous immunoglobulin is not routinely recommended as it does not impact overall survival 1
• Monitor for Richter's transformation (transformation to aggressive lymphoma) in CLL patients with sudden clinical deterioration 1

Treatment Response Evaluation

• Response evaluation should include physical examination and blood counts 1
• Complete remission defined by normalization of lymphocytosis and disappearance of all clinical manifestations 1
• Bone marrow biopsy recommended for confirmation of complete remission, particularly in clinical trials 1

Pitfalls to Avoid

• Do not initiate treatment based solely on lymphocytosis without other criteria for active disease 1
• Do not mistake transient lymphocytosis due to infections for hematologic malignancy 1
• Avoid premature discontinuation of BTKi therapy due to early lymphocytosis, which is an expected effect 1
• Do not overlook evaluation for underlying infections in patients with lymphocytosis, particularly in cases with HLH 3, 4