Does Myelodysplastic Syndromes (MDS) cause elevated White Blood Cell (WBC) count?

Myelodysplastic Syndromes and White Blood Cell Count

Myelodysplastic Syndromes (MDS) typically do not cause elevated white blood cell counts; in fact, MDS is more commonly associated with lower WBC counts as part of the ineffective hematopoiesis characteristic of the disease. 1

Typical Hematological Findings in MDS

• Cytopenias: MDS is characterized by persistent cytopenias affecting one or more cell lines:

  • Anemia (most common presentation)
  • Neutropenia
  • Thrombocytopenia

• WBC patterns in MDS:

  • Lower WBC counts are typically observed in MDS patients with splicing factor mutations 1
  • Biologic evidence indicates that MDS patients commonly present with lower WBC counts, not elevated counts 1

MDS Subtypes and WBC Patterns

Different MDS subtypes show distinct WBC patterns:

1. Pure MDS:

   • Generally associated with normal to low WBC counts
   • Characterized by ineffective hematopoiesis where cells die in the bone marrow before maturing (apoptosis) 2

2. MDS/MPN Overlap Syndromes:

   • Some MDS/MPN overlap syndromes may present with elevated WBC counts, particularly:
     • Chronic Myelomonocytic Leukemia (CMML): Classified into proliferative-type CMML (WBC ≥13 × 10^9/L) and dysplastic-type CMML (WBC <13 × 10^9/L) 1
     • Atypical Chronic Myeloid Leukemia (aCML): May present with neutrophilia 1

Diagnostic Considerations

When evaluating a patient with elevated WBC count and suspected MDS:

• Consider MDS/MPN overlap syndromes rather than pure MDS 1

• Evaluate for specific genetic markers:

  • JAK2 mutations if thrombocytosis is present (suggests myeloproliferative component) 1
  • CSF3R mutations (associated with chronic neutrophilic leukemia rather than MDS) 1
  • SETBP1 or ETNK1 mutations (found in up to one-third of aCML cases) 1

• Perform comprehensive diagnostic workup:

  • Complete blood count with differential
  • Bone marrow aspiration and biopsy
  • Cytogenetic analysis
  • Molecular testing 3

Clinical Implications

The presence of elevated WBC count in a patient with suspected MDS has important diagnostic and prognostic implications:

• It may indicate an MDS/MPN overlap syndrome rather than pure MDS 1
• Proliferative-type CMML (with elevated WBC) was specifically excluded from the International Prognostic Scoring System (IPSS) for MDS due to its distinct clinical behavior 1
• The WBC count is an important factor in risk stratification and treatment decisions 1

Common Pitfalls

• Misdiagnosing MDS/MPN overlap syndromes as pure MDS
• Failing to recognize that elevated WBC is atypical for pure MDS and warrants further investigation
• Not considering other causes of cytopenia with elevated WBC (infections, inflammatory conditions)
• Overlooking the need for cytogenetic and molecular testing to properly classify the disease

In summary, pure MDS typically presents with normal to low WBC counts, and an elevated WBC count should prompt consideration of MDS/MPN overlap syndromes or other diagnoses.