What is the significance of leukocytosis (elevated white blood cell count) with neutrophilia (elevated neutrophil count) in a patient with myelodysplastic syndrome (MDS)?

Significance of Elevated Neutrophil Count in Myelodysplastic Syndrome

Extremely elevated neutrophil count (neutrophilia) in a patient with myelodysplastic syndrome (MDS) should raise immediate concern for disease progression, transformation to acute myeloid leukemia (AML), or development of a concurrent myeloproliferative component. This finding requires urgent evaluation as it may significantly impact prognosis and treatment decisions.

Clinical Significance and Differential Diagnosis

Neutrophilia in MDS is unusual and concerning for several reasons:

1. Disease Progression Marker

   • MDS typically presents with cytopenias (low blood counts), including neutropenia
   • Sudden neutrophilia may represent disease evolution or progression 1
   • May indicate transformation to a more aggressive MDS subtype

2. Potential Transformation to AML

   • High neutrophil counts may signal impending transformation to AML
   • Risk of transformation varies by MDS subtype: 5-15% in low-risk MDS vs. 40-50% in high-risk MDS 1
   • Transformation to AML is defined as ≥30% blasts in bone marrow 1

3. Overlap MDS/MPN Syndrome

   • May represent evolution to a mixed MDS/myeloproliferative neoplasm (MPN) such as:
     • Chronic myelomonocytic leukemia (CMML)
     • Atypical chronic myeloid leukemia (aCML)
   • These overlap syndromes have distinct prognostic implications 1

4. Infection or Inflammation

   • Always rule out concurrent infection or inflammatory process
   • Unlike reactive neutrophilia, clonal neutrophilia in MDS often includes dysplastic features

Diagnostic Approach

When neutrophilia is detected in an MDS patient:

1. Urgent Bone Marrow Evaluation

   • Complete bone marrow aspiration and biopsy
   • Assess blast percentage (critical for determining progression)
   • Evaluate for dysplastic features in neutrophil lineage
   • Cytogenetic analysis to detect new chromosomal abnormalities 1

2. Peripheral Blood Assessment

   • Evaluate for circulating blasts
   • Assess for dysplastic features in neutrophils (hypogranulation, Pelger-Huët anomaly) 2, 3
   • Functional neutrophil studies may reveal impaired activity despite high numbers 3

3. Molecular Testing

   • Test for mutations associated with disease progression
   • Evaluate for MPN-associated mutations (JAK2, CALR, MPL) 1
   • Consider testing for CSF3R mutations (associated with CNL but rare in aCML) 1

Prognostic Implications

The finding of neutrophilia in MDS significantly impacts prognosis:

1. Risk Stratification

   • Requires reassessment using the International Prognostic Scoring System (IPSS) 1
   • May result in reclassification to a higher risk category

2. Survival Impact

   • High-risk MDS patients have median survival of less than 3 years 4
   • Transformation to AML further reduces survival to months 1
   • Patients with MDS/MPN overlap syndromes have distinct prognostic profiles

3. Treatment Implications

   • May necessitate shift from supportive care to disease-modifying therapy
   • Higher-risk disease may warrant consideration of hypomethylating agents 1
   • Allogeneic stem cell transplantation may need to be considered sooner 1, 4

Management Considerations

Based on the finding of neutrophilia in MDS:

1. Treatment Intensification

   • If progression to higher-risk MDS is confirmed, consider:
     • Hypomethylating agents (azacitidine, decitabine) 1, 4
     • Evaluation for stem cell transplantation eligibility 1

2. Monitoring

   • Increase frequency of blood count monitoring
   • Regular bone marrow assessments to track disease evolution
   • Monitor for signs of infection despite neutrophilia (neutrophil function may be impaired) 3

Common Pitfalls

1. Misinterpreting Reactive Neutrophilia

   • Always rule out infection, inflammation, or medication effect
   • Clonal neutrophilia typically persists despite treating potential triggers

2. Overlooking Functional Neutrophil Defects

   • High neutrophil counts may not provide normal immune protection
   • Neutrophils in MDS often have impaired function despite normal or elevated counts 3

3. Delaying Bone Marrow Assessment

   • Prompt bone marrow evaluation is essential when neutrophilia develops
   • Delay may miss early disease transformation

4. Failing to Reassess Risk Classification

   • Neutrophilia may change the patient's risk category
   • Treatment should be adjusted based on updated risk assessment

In summary, neutrophilia in MDS represents a significant clinical finding that warrants immediate evaluation to determine its cause and implications for disease progression, treatment approach, and overall prognosis.