What are the next steps in managing a 10-year-old patient with anemia, elevated absolute eosinophil and basophil counts, and a normal platelet count, considering the possibility of chronic myeloid leukemia (CML)?

Management of Suspected CML in a 10-Year-Old with Anemia, Eosinophilia, Basophilia, and Normal Platelet Count

Immediately refer this patient to pediatric hematology/oncology for same-day evaluation and initiate urgent diagnostic testing for chronic myeloid leukemia, as the combination of anemia with elevated eosinophils and basophils creates a pattern highly suspicious for a clonal myeloproliferative process regardless of normal platelet count. 1

Urgent Diagnostic Workup

Obtain these tests immediately without delay:

• Peripheral blood smear review by an experienced pathologist/hematologist same-day to identify blasts, immature granulocytes, basophilia, eosinophilia, and platelet morphology 1, 2
• BCR::ABL1 fusion gene testing via quantitative RT-PCR and Philadelphia chromosome analysis via cytogenetic analysis—these are the definitive diagnostic tests for CML 1, 3
• Complete metabolic panel including uric acid, LDH, potassium, and phosphate to assess for tumor lysis syndrome parameters 2, 4
• Bone marrow aspirate and biopsy with cytogenetic analysis to detect Ph chromosome and any additional chromosomal abnormalities 3

The presence of elevated eosinophils and basophils together strongly suggests a myeloproliferative disorder, particularly CML, as basophilia is a hallmark feature and eosinophils may be prominent in CML bone marrow 1. Anemia in combination with these findings indicates involvement of multiple cell lines, which is inconsistent with a benign reactive process 1.

Critical Clinical Assessment

Evaluate immediately for these features:

• Constitutional symptoms: fever, night sweats, weight loss, decreased appetite, fatigue severity 1, 2
• Physical examination: splenomegaly, hepatomegaly, lymphadenopathy 1
• Bleeding manifestations: petechiae, ecchymoses, or active bleeding—20% of children with CML present with bleeding despite normal or elevated platelet counts 3, 2
• Signs of leukostasis: respiratory distress, altered mental status, visual changes (though uncommon in children, occurring in only 16.5% of pediatric CML cases) 3
• In boys: assess for priapism, which occurs in 2.5-3.3% of boys at CML diagnosis and requires emergency management 3

Initial Management Based on White Blood Cell Count

If WBC >100 × 10⁹/L or Signs of Leukostasis:

Start immediately:

• Intravenous hyperhydration at 2.5-3 liters/m²/day, titrated according to fluid balance and clinical status 3, 4
• Hydroxyurea 25-50 mg/kg/day in 2-3 divided doses for rapid cytoreduction 3, 4
• Monitor for tumor lysis syndrome with serial electrolytes, uric acid, LDH, phosphate, and calcium 3, 4
• Allopurinol only if TLS parameters are deranged or uric acid rises after starting therapy—routine use is not required as TLS is rare in pediatric CML-CP 3

If organ-threatening leukostasis develops (cerebral, pulmonary, or priapism), leukapheresis or exchange transfusion provides 30-80% WBC reduction within hours and is required as emergency cytoreduction 3.

If WBC <100 × 10⁹/L Without Leukostasis:

• Oral hydration is sufficient 3
• Hydroxyurea may still be initiated if WBC is elevated and symptomatic 3

Definitive Treatment Upon BCR::ABL1 Confirmation

Once BCR::ABL1 fusion is confirmed, immediately initiate tyrosine kinase inhibitor (TKI) therapy—every day without TKI represents lost opportunity for achieving optimal molecular responses that predict long-term survival. 4

TKI Selection Based on ELTS Risk Score:

Calculate ELTS (EUTOS Long-Term Survival) score using age, spleen size, platelet count, and blast percentage to stratify risk 3. In the pediatric cohort, 3-year progression-free survival was 97.1% for low-risk, 91.7% for intermediate-risk, and 72.0% for high-risk patients on imatinib 3.

• Low-to-intermediate ELTS risk: Start imatinib 300 mg/m² daily (maximum 400 mg/m²) 3
• High ELTS risk: Start second-generation TKI (dasatinib or nilotinib) as first-line therapy 3
• Consider bosutinib for all newly diagnosed pediatric patients if growth impairment is a concern, as it has limited impact on growth during the first year compared to other TKIs 3

Taper hydroxyurea over 3-5 days once TKI therapy is initiated 4. Hydroxyurea should never be used as definitive treatment—its role is strictly limited to temporary cytoreduction before TKI initiation 4.

Monitoring Response to TKI Therapy

Complete hematologic response (CHR) should be achieved within 3 months, defined as: 3

• WBC <10 × 10⁹/L
• Normal differential count
• Normal platelet count
• Non-palpable spleen
• Disappearance of symptoms

Monitor blood counts every 2 weeks until CHR is achieved 3, 4.

Molecular response milestones: 3

• Month 3: BCR::ABL1 <10% (optimal response)
• Month 6: BCR::ABL1 <1% (optimal response)
• Month 12: BCR::ABL1 <0.1% (optimal response)

If BCR::ABL1 >10% at 3 months or >10% at 6 months, consider dose escalation of imatinib (if plasma level <1000 ng/mL) or switch to second/third-generation TKI 3.

Critical Pitfalls to Avoid

• Do not delay hematology referral waiting for BCR::ABL1 results—refer immediately based on clinical suspicion 1, 2
• Do not dismiss bleeding risk because platelet count is normal—20% of pediatric CML patients present with bleeding despite normal/elevated platelets due to acquired von Willebrand syndrome 3
• Do not use low-dose aspirin for thrombocytosis in children due to risk of Reye syndrome and platelet dysfunction 3
• Do not continue hydroxyurea beyond brief cytoreduction period—TKI therapy must be started immediately upon BCR::ABL1 confirmation 4
• Do not assume absence of leukostasis based on WBC alone—it can occur at lower counts, though it typically requires much higher WBC in pediatric CML 3

Special Considerations for Bleeding Management

If bleeding occurs despite normal platelet count, consider acquired von Willebrand syndrome, which occurs in children with CML-CP presenting with high platelet counts 3. Treatment options include: 3

• Desmopressin
• Fresh frozen plasma (for severe bleeding)
• Von Willebrand factor concentrates
• Intravenous immunoglobulin
• Recombinant factor VIIa

Emergency imaging is required if CNS symptoms develop to rule out intracerebral hemorrhage 3.

TKI treatment results in remission of acquired von Willebrand syndrome within 2-4 weeks 3.