What is the best course of action for a patient with a decreased lymphocyte count, elevated white blood cell (WBC) count, and potential symptoms of a myeloproliferative disorder, who is being treated with hydroxyurea and aspirin, but not for polycythemia vera (PV)?

Management of Myeloproliferative Disorder with Elevated WBC and Decreased Lymphocytes on Hydroxyurea

If this patient has a myeloproliferative neoplasm other than polycythemia vera (such as essential thrombocythemia or primary myelofibrosis), continue hydroxyurea and aspirin while closely monitoring blood counts, as this represents standard first-line cytoreductive therapy for high-risk disease. 1

Diagnostic Clarification Required

The clinical scenario requires immediate clarification of which specific myeloproliferative neoplasm is present:

• Essential Thrombocythemia (ET): Hydroxyurea plus aspirin is appropriate first-line therapy for high-risk patients (age >60 years or thrombosis history) 1
• Primary Myelofibrosis (PMF): Hydroxyurea is used for cytoreduction in symptomatic disease with elevated WBC counts 1
• Chronic Myeloid Leukemia (CML): Hydroxyurea is indicated for resistant disease 2

The statement "not being treated for PV" suggests the patient has a different MPN diagnosis where hydroxyurea remains appropriate therapy.

Current Treatment Assessment

The combination of hydroxyurea and aspirin is guideline-concordant for high-risk myeloproliferative neoplasms other than PV. 1

Monitoring for Hydroxyurea Toxicity

The decreased lymphocyte count warrants evaluation for hydroxyurea-induced myelosuppression. Immediately check complete blood counts including absolute neutrophil count, platelet count, and hemoglobin to assess for intolerance criteria: 1, 3

• Absolute neutrophil count <1.0 × 10⁹/L = mandatory discontinuation 1, 3, 2
• Platelet count <100 × 10⁹/L (for PV/ET) or <50 × 10⁹/L (for PMF) = intolerance criterion 1, 3
• Hemoglobin <10 g/dL = mandatory discontinuation 1, 3, 2

Evaluating Hydroxyurea Resistance

After 3 months of adequate hydroxyurea dosing (at least 2 g/day, or 2.5 g/day if body weight >80 kg), assess for resistance criteria: 1, 3

For Essential Thrombocythemia:

• Platelet count >600 × 10⁹/L despite adequate dosing 1, 3
• Platelet count >400 × 10⁹/L with hemoglobin <10 g/dL 1

For Primary Myelofibrosis or other MPNs:

• Uncontrolled myeloproliferation: platelet count >400 × 10⁹/L AND WBC count >10 × 10⁹/L 1, 3
• Progressive splenomegaly or uncontrolled symptoms 1

Management Algorithm

Step 1: Assess Current Blood Counts

• If ANC <1.0 × 10⁹/L, platelets <100 × 10⁹/L, or Hgb <10 g/dL → Hold hydroxyurea immediately 3, 2
• If counts are above these thresholds → Continue current therapy with weekly monitoring 2

Step 2: Evaluate Disease Control

• If WBC >10 × 10⁹/L and platelets >400 × 10⁹/L after 3 months of adequate hydroxyurea dosing → Consider resistance and second-line therapy 1, 3
• If disease is controlled → Continue current regimen 1

Step 3: Second-Line Options if Resistance/Intolerance Confirmed

The European LeukemiaNet and ESMO guidelines recommend the following second-line agents: 1

1. Interferon-alpha (pegylated preferred): First choice for younger patients, those with reproductive concerns, or hydroxyurea intolerance 1
2. Ruxolitinib: For patients with severe symptoms, splenomegaly, or intolerance to both hydroxyurea and interferon 1
3. Busulfan: Reserved for elderly patients (>70 years) with short life expectancy 1

Critical Monitoring Parameters

Weekly complete blood counts are mandatory during hydroxyurea therapy, particularly when evaluating for toxicity: 2

• Absolute neutrophil count
• Platelet count
• Hemoglobin/hematocrit
• White blood cell count with differential

Additional monitoring for hydroxyurea toxicity includes: 2

• Skin examination for leg ulcers or mucocutaneous manifestations (discontinuation criterion) 1, 3, 2
• Hepatic and renal function 2
• Signs of hemolytic anemia (jaundice, hematuria, elevated LDH, low haptoglobin) 2

Aspirin Continuation

Continue low-dose aspirin (81-100 mg daily) unless contraindications develop: 1

• Major bleeding events warrant aspirin discontinuation 1
• Extreme thrombocytosis (>1500 × 10⁹/L) may require caution due to acquired von Willebrand disease risk 1, 4

Common Pitfalls to Avoid

Do not escalate hydroxyurea beyond 2 g/day (2.5 g/day if >80 kg) when assessing for resistance - this is the threshold dose for defining treatment failure, not a target to exceed 1, 3

Do not attribute isolated lymphopenia to disease progression without ruling out hydroxyurea toxicity first - check all cell lines and assess for other cytopenias 2

Do not delay switching to second-line therapy if clear resistance or intolerance criteria are met - prolonged exposure to failing hydroxyurea therapy increases leukemic transformation risk without benefit 1