What is the management approach for patients with leukocytosis and thrombocytosis?

Management of Leukocytosis and Thrombocytosis

For patients with symptomatic leukocytosis and thrombocytosis, hydroxyurea is the first-line treatment option, with alternative options including apheresis, tyrosine kinase inhibitors (for CML), or clinical trials depending on the underlying cause. 1

Diagnostic Approach

• Determine whether the condition is reactive or clonal (myeloproliferative neoplasm) 2, 3
• For suspected chronic myeloid leukemia (CML), confirm diagnosis with fluorescence in situ hybridization (FISH) on peripheral blood using dual probes for BCR and ABL genes 1
• For suspected essential thrombocythemia (ET), evaluate for JAK2, CALR, and MPL mutations 4
• Consider bone marrow examination to distinguish between different myeloproliferative neoplasms 4

Risk Assessment

• Evaluate risk factors for thromboembolic disease including:
  • Age >60 years 1
  • Prior history of thrombosis 1
  • Cardiovascular risk factors 1
  • Degree of thrombocytosis (platelet count >1,000 x 10^9/L increases bleeding risk) 1
  • Presence of JAK2 mutation (increases thrombosis risk) 4

Management Algorithm for Symptomatic Leukocytosis

1. For significant leukocytosis (WBC >30,000/μL) with symptoms:

   • Initiate hydroxyurea (2-4g per day) as first-line therapy 5
   • Consider apheresis for severe symptoms of leukostasis 1
   • For CML, tyrosine kinase inhibitors like imatinib are preferred 1

2. For asymptomatic leukocytosis:

   • Monitor without cytoreductive therapy if no other indications exist 5
   • Consider treatment if progressive increase in counts or development of symptoms 1

Management Algorithm for Symptomatic Thrombocytosis

1. For symptomatic thrombocytosis:

   • Hydroxyurea is first-line therapy 1
   • Additional options include antiaggregants (aspirin 81-100 mg daily) 1
   • Consider anagrelide as second-line therapy for ET 1
   • Apheresis for extreme thrombocytosis with acute symptoms 1

2. For asymptomatic thrombocytosis:

   • Low-dose aspirin for all patients with ET, twice daily for low-risk disease 4
   • Cytoreductive therapy for high-risk patients (age >60 years and/or prior thrombosis) 1, 4
   • Optional cytoreductive therapy for intermediate-risk patients 4

Special Considerations

• In CML patients: Monitor BCR-ABL transcript levels every 3 months during treatment 1
• In ET patients: Consider twice-daily low-dose aspirin for low-risk disease 4
• For pregnant patients: Interferons (alfa-2b, peginterferon alfa-2a, or peginterferon alfa-2b) are preferred over hydroxyurea 1
• For extreme thrombocytosis (>1,500 x 10^9/L): Cytoreductive therapy should be considered even in otherwise low-risk patients due to increased bleeding risk 1

Monitoring Response to Treatment

• Complete hematologic response criteria include:
  • Leukocyte count <10 x 10^9/L 1
  • Platelet count <450 x 10^9/L 1
  • No immature cells in peripheral blood 1
  • No signs/symptoms of disease with disappearance of palpable splenomegaly 1

Dose Adjustments and Management of Side Effects

• For Grade 3-4 neutropenia (ANC <1000/mm^3): Hold drug until ANC ≥1500/mm^3, then resume at reduced dose 1
• For Grade 3-4 thrombocytopenia (platelets <50,000/mm^3): Hold drug until platelets ≥75,000/mm^3, then resume at reduced dose 1
• Growth factors can be used in combination with therapy for resistant cytopenias 1
• For fluid retention: Manage with diuretics and supportive care 1

Common Pitfalls to Avoid

• Do not automatically discontinue therapy due to mild-moderate leukocytosis without symptoms 5
• Avoid misinterpreting treatment-related leukocytosis as disease progression 5
• Do not initiate aggressive cytoreductive therapy for asymptomatic mild-moderate leukocytosis 5
• Remember that thrombocytosis (platelet count >1,000 x 10^9/L) has been associated with immediate risk of major hemorrhage rather than thrombosis in ET patients 1