What is the appropriate management for a patient with leukocytosis and anemia?

Management of Leukocytosis with Anemia

The patient requires urgent evaluation for a myeloproliferative disorder or chronic myelomonocytic leukemia (CMML), with bone marrow aspiration and biopsy as the next appropriate step to establish diagnosis and guide treatment. 1

Assessment of Current Laboratory Findings

The patient presents with:

• Leukocytosis (WBC 11.8 K/mcL) with neutrophilia (absolute neutrophil count 8.93 K/mcL)
• Anemia (Hb 12.7-13.2 g/dL, below reference range)
• Relative lymphopenia (14.2%, below reference range)
• Normal platelets (345 K/mcL)
• Consistent pattern of anemia over 3 years with recent worsening

Key Diagnostic Considerations

1. Myeloproliferative disorder pattern:

   • The combination of leukocytosis with neutrophilia and persistent anemia strongly suggests a myeloproliferative process
   • The chronicity of the anemia (present for at least 3 years) with recent worsening and development of leukocytosis points to a progressive bone marrow disorder

2. Differential diagnosis:

   • Chronic myelomonocytic leukemia (CMML)
   • Other myeloproliferative neoplasms
   • Reactive leukocytosis with separate cause of anemia
   • Infection or inflammatory process

Management Algorithm

Step 1: Immediate Diagnostic Workup

• Bone marrow aspiration and biopsy with cytogenetic analysis
• Peripheral blood flow cytometry
• Serum erythropoietin level (for patients with Hb ≤ 10 g/dL) 1
• Evaluation for other causes of leukocytosis (infection, inflammation)
• Assessment for splenomegaly (physical exam and imaging)

Step 2: Disease Classification

Based on bone marrow findings, classify as:

• Myelodysplastic (MD) CMML: If primarily characterized by cytopenias
• Myeloproliferative (MP) CMML: If characterized by proliferative features with WBC >10 × 10^9/L 1
• Other myeloproliferative disorder
• Non-malignant cause

Step 3: Treatment Based on Classification

For MD-CMML with <10% blasts:

• Supportive therapy to correct cytopenias
• For anemia with Hb ≤ 10g/dL and serum erythropoietin ≤ 500 mU/dL, initiate erythropoietic stimulating agents 1

For MP-CMML with low blast count:

• Cytoreductive therapy with hydroxyurea as first-line treatment to control proliferative myelomonocytic cells 1

For either type with high blast count (≥10% in BM):

• Consider hypomethylating agents (5-azacytidine or decitabine)
• Evaluate eligibility for allogeneic stem cell transplantation, especially for patients <65 years 1

Specific Management of Anemia

1. Determine severity and cause:

   • Current Hb is mildly decreased (12.7-13.2 g/dL)
   • If anemia worsens to Hb ≤ 10 g/dL, check serum erythropoietin levels

2. Treatment options:

   • For severe symptomatic anemia (Hb < 8 g/dL), consider RBC transfusions
   • Restrict transfusions to the minimum number of units required to relieve symptoms or return to safe Hb range (7-8 g/dL) 1
   • For eligible patients, consider erythropoiesis-stimulating agents (ESAs) 2

Important Considerations and Pitfalls

1. ESA therapy cautions:

   • ESAs increase risk of thromboembolism, particularly in cancer patients
   • Target Hb should not exceed 11 g/dL due to increased cardiovascular risks 2
   • ESAs are contraindicated if malignancy is being treated with curative intent 2

2. Monitoring requirements:

   • Regular CBC with differential
   • Bone marrow reassessment if disease progresses
   • Monitor for splenomegaly development or progression

3. Common pitfalls to avoid:

   • Treating leukocytosis without establishing underlying cause
   • Attributing findings to infection without excluding malignancy
   • Delaying bone marrow evaluation in patients with persistent unexplained cytopenias
   • Overlooking the need for cytogenetic analysis which provides important prognostic information

The combination of leukocytosis with chronic anemia requires thorough evaluation to rule out myeloproliferative disorders, particularly CMML. Early diagnosis and appropriate classification are essential for optimal management and improved outcomes.