What is refractory cytopenia with blast cells?

Refractory Cytopenia with Blast Cells: Definition and Classification

Refractory cytopenia with blast cells is a subtype of myelodysplastic syndrome (MDS) characterized by persistent cytopenia(s) with dysplastic changes in bone marrow cells and an increased percentage of blast cells, indicating a higher risk of progression to acute myeloid leukemia (AML). 1

Classification Based on Blast Percentage

According to the World Health Organization (WHO) classification, refractory cytopenia with blast cells falls into specific categories based on blast percentage:

RAEB-1 (Refractory Anemia with Excess Blasts-1):

• 2-4% blasts in peripheral blood OR
• 5-9% blasts in bone marrow
• Represents an intermediate-risk MDS 1

RAEB-2 (Refractory Anemia with Excess Blasts-2):

• 5-19% blasts in peripheral blood OR
• 10-19% blasts in bone marrow OR
• Presence of Auer rods (regardless of blast percentage) 1, 2
• Higher risk of progression to AML 1

Diagnostic Criteria

The diagnosis of MDS with excess blasts requires:

• Persistent cytopenia(s) for at least 4-6 months 1
• Exclusion of other potential causes of cytopenia and dysplasia 1
• At least one of the following MDS-related criteria:
  • Dysplasia (≥10% in at least one major bone marrow lineage)
  • Blast cell count of 5-19%
  • MDS-associated karyotype (e.g., del(5q), del(20q), +8, or -7/del(7q)) 1

Clinical Significance

The presence of increased blast cells in MDS has significant prognostic implications:

• Disease Progression Risk: Higher blast percentages correlate with increased risk of progression to AML 1, 3
• Survival Impact: RAEB-2 has a median survival of approximately 18 months compared to 24 months for intermediate forms and much longer for low-risk MDS 4
• Treatment Decisions: Patients with increased blasts typically require more aggressive treatment approaches than those with lower-risk MDS 1

Special Considerations

Auer Rods

• The presence of Auer rods automatically classifies a case as RAEB-2, regardless of blast percentage 1, 2
• This reflects the aggressive biology and high likelihood of progression to AML 2

Multilineage Dysplasia

• Refractory cytopenia with multilineage dysplasia (RCMD) with increased blasts has worse outcomes than unilineage dysplasia 4
• Patients with multilineage dysplasia show more severe cytopenias and higher frequency of cytogenetic abnormalities 4

Pediatric Cases

• In children, refractory cytopenia of childhood (RCC) is a provisional entity with different diagnostic criteria and generally better prognosis than adult MDS 1, 5
• Children with increased blasts are classified using the same criteria as adults 1

Monitoring and Prognosis

• Regular monitoring of blast percentage is essential as increases may indicate disease progression 6
• Flow cytometry analysis of bone marrow blast region composition may help predict progression risk 6
• Cytogenetic abnormalities, particularly involving chromosomes 5 and 7 or complex karyotypes, are associated with worse outcomes 4

Pitfalls in Diagnosis

• Hypocellular or fibrotic bone marrow can make blast enumeration difficult; immunohistochemistry for CD34 on bone marrow biopsy may be helpful 1
• Distinction from other myeloid neoplasms with fibrosis can be challenging 1
• Flow cytometric abnormalities alone are not diagnostic of MDS and must be correlated with morphologic findings 1

The accurate classification of refractory cytopenia with blast cells is crucial for determining prognosis and guiding treatment decisions, with higher blast percentages indicating more aggressive disease requiring more intensive therapeutic approaches.