Does Normal WBC Count Rule Out CML in This Case?
No, a normal white blood cell count does NOT rule out chronic myeloid leukemia (CML) in a 10-year-old with elevated absolute eosinophil and basophil counts, anemia, and thrombocytopenia with low mean platelet volume—this presentation requires immediate hematology/oncology referral and BCR::ABL1 fusion testing regardless of the total WBC count. 1, 2
Why Normal WBC Does Not Exclude CML
Preleukemic CML Presentation
CML can present with normal or only mildly elevated WBC counts in a preleukemic phase (pre-CML). A study of 7 patients with confirmed BCR::ABL1-positive CML demonstrated WBC counts ranging from 3.6 to 14.3 K/mm³ (normal to mildly elevated) with 0% blasts, yet all had cytogenetic evidence of t(9;22) and BCR::ABL1 fusion confirming CML diagnosis. 3
The presence of absolute basophilia (≥200/mm³) was noted in 4 of 7 pre-CML cases, making this a key diagnostic clue even when WBC is normal. 3 Your patient has elevated basophils, which is highly suspicious.
Critical Diagnostic Features Present in This Case
Red flags that mandate immediate workup regardless of WBC:
Elevated eosinophils AND basophils together strongly suggest a myeloproliferative disorder, particularly CML, as basophilia is common and eosinophils may be prominent in CML bone marrow. 4
Thrombocytopenia with LOW mean platelet volume is particularly concerning. While CML often presents with thrombocytosis, patients with CML and normal or low platelet counts demonstrate more heterogeneous and abnormal thrombopoiesis with dysmegakaryocytes. 5 Low MPV with thrombocytopenia suggests cytotoxic processes or marrow dysfunction, which can occur in myeloproliferative disorders. 6
Anemia in combination with these findings indicates involvement of multiple cell lines, which is inconsistent with a benign reactive process. 1, 2
Immediate Diagnostic Algorithm
Step 1: Urgent peripheral blood smear review 1, 2
- Look specifically for: blasts, immature granulocytes, basophilia, eosinophilia, and platelet morphology
- Must be reviewed by experienced pathologist/hematologist same-day
Step 2: Immediate hematology/oncology referral 1, 2
- Do NOT wait for additional testing
- Cytopenias in other cell lines (anemia, thrombocytopenia) mandate immediate referral 1
Step 3: Order BCR::ABL1 fusion gene testing and Philadelphia chromosome analysis 2, 7
- This is the definitive diagnostic test for CML
- Approximately 90% of CML patients present in chronic phase with <10% blasts 8
Step 4: Baseline metabolic panel for tumor lysis syndrome parameters 1, 2
- Check uric acid, LDH, potassium, phosphate, calcium, creatinine
- Even without hyperleukocytosis, assess for metabolic derangements
Key Clinical Pitfall to Avoid
The most dangerous error is assuming a normal WBC count excludes serious hematologic malignancy. 3 The combination of:
- Elevated eosinophils + basophils (dual lineage abnormality)
- Anemia (erythroid line involvement)
- Thrombocytopenia with low MPV (megakaryocyte dysfunction)
...creates a pattern highly suspicious for a clonal myeloproliferative process, regardless of total WBC. 3, 5
Bone Marrow Findings That Support Pre-CML
If bone marrow examination is performed, look for: 3
- Increased microvascular density (approximately 10 vessels/200× field vs. 5 in reactive processes)
- Tortuous microvessels with abnormal branching on CD34 staining
- Small, hypolobated megakaryocytes (approximately 40% in pre-CML vs. 13% in leukemoid reaction) highlighted by CD61
- These findings distinguish pre-CML from leukemoid reaction even with normal WBC
Constitutional Symptoms Assessment
- Fever, night sweats, weight loss
- Decreased appetite (present in many pediatric CML cases)
- Fatigue severity
- Bone or joint pain
- Splenomegaly or hepatomegaly on examination
Any constitutional symptoms with these laboratory abnormalities further elevate urgency for malignancy workup. 1, 2