Is a 20% blast count a definitive cutoff between Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukemia (AML)?

Is 20% a Hard Cutoff Between MDS and AML?

No, the 20% blast threshold is not a hard cutoff between MDS and AML, as therapeutic decisions should be based not only on blast percentage but also on clinical features, disease progression rate, and genetic data.

Historical Context and Current Classification

• The 2001 WHO classification lowered the blast threshold for AML diagnosis from 30% (FAB classification) to 20%, reclassifying patients with 20-29% blasts from RAEB-T (under FAB) to AML with multilineage dysplasia 1
• This change was based on studies suggesting patients with 20-29% blasts often have clinical features, response to therapy, and survival times similar to patients with ≥30% blasts 1

Clinical Considerations Beyond Blast Percentage

• The NCCN panel recognizes that MDS and AML classification should consider not only blast quantitation but also the distinctive biologic features and pace of disease 1
• NCCN guidelines classify patients with 20-29% marrow blasts as "MDS-EB in transformation (MDS-EB-T)" and recommend they be considered as either MDS or AML 1
• Patients with 20-29% blasts and a stable clinical course for ≥2 months may be considered as having either MDS or AML 1

Factors to Consider in Treatment Decision-Making

• Treatment decisions for patients with 20-29% blasts should be individualized based on:
  • Age and performance status 1
  • Antecedent factors and disease history 1
  • Cytogenetic and molecular genetic data 1
  • Rate of disease progression 1
  • Comorbidities 1
  • Patient's treatment goals 1

Clinical Behavior and Outcomes

• Some patients with prior MDS and 20-29% bone marrow blasts may behave clinically more similar to MDS than to AML 1
• Recent research suggests that patients with 10-30% blasts share similar clinical and biological features, challenging the rigid 20% cutoff 2
• A Seattle study found that after accounting for risk factors, age, performance status, and treatment including transplantation, patients with WHO-defined AML had similar survival and response rates as patients with MDS-EB2 (10-19% blasts) 2

Age-Related Considerations

• In younger patients (≤60 years), intensive AML-type therapy resulted in similar outcomes regardless of blast percentage 3
• In older patients (≥70 years), those with 20-29% blasts had outcomes similar to patients with <20% blasts and better than those with ≥30% blasts 3
• For older patients, epigenetic therapy provided at least equivalent outcomes to intensive chemotherapy 3

Common Pitfalls to Avoid

• Relying solely on blast percentage without considering other clinical and biological factors may lead to suboptimal treatment decisions 1
• Excluding patients with borderline blast percentages (19% or 21%) from clinical trials limits treatment options and research progress 2
• Failing to consider the patient's age and comorbidities when deciding between MDS-directed versus AML-directed therapy 3
• Not recognizing that the method of blast counting (biopsy vs. aspirate) can affect classification and prognosis 4

Practical Approach

1. Determine blast percentage accurately using both bone marrow biopsy and aspirate 4
2. Consider genetic and molecular features that may influence prognosis and treatment response 1
3. Evaluate patient factors including age, performance status, and comorbidities 1
4. For patients with 20-29% blasts:
   • If younger with good performance status, consider AML-directed therapy 3
   • If older or with significant comorbidities, MDS-directed therapy may be appropriate 3
   • For patients with prior MDS history and stable disease, MDS-directed therapy may be reasonable 1