What are the diagnostic criteria for Acute Myeloid Leukemia (AML) in adults?

Diagnostic Criteria for Acute Myeloid Leukemia (AML) in Adults

The diagnosis of AML in adults requires examination of peripheral blood and bone marrow samples with a minimum of 20% blasts in either specimen, along with comprehensive workup including morphological examination, cytochemistry, immunophenotyping, cytogenetics, and molecular genetics. 1, 2

Core Diagnostic Requirements

• Bone marrow aspirate and/or peripheral blood examination is essential, with evaluation of at least 500 nucleated cells 1
• Presence of ≥20% myeloblasts in bone marrow or peripheral blood is required for most AML diagnoses 2, 1
• In AML with monocytic differentiation, monoblasts and promonocytes (but not abnormal monocytes) are counted as blast equivalents 3
• Some AML subtypes with specific genetic abnormalities (including NPM1 mutation) may be diagnosed with ≥10% blasts 4

Essential Diagnostic Studies

• Morphological examination:

  • Evaluation of peripheral blood smear 1
  • Bone marrow aspirate smears for morphologic assessment 1
  • Bone marrow trephine core biopsy 1

• Cytochemistry:

  • Nonspecific esterase (NSE) stains show diffuse cytoplasmic activity in approximately 80% of monoblasts 3

• Immunophenotyping:

  • Flow cytometry with a panel sufficient to distinguish AML from other acute leukemias 1
  • Markers to identify myeloid lineage and detect aberrant antigen expression 1

• Cytogenetic analysis:

  • Conventional karyotyping is mandatory for proper classification 1
  • FISH for rapid detection of specific abnormalities 1

• Molecular genetic testing:

  • FLT3-ITD testing in all patients 1
  • NPM1, CEBPA, and RUNX1 mutation analysis for non-CBF AML, non-APL cases 1
  • KIT mutation analysis for CBF AML (with t(8;21) or inv(16)/t(16;16)) 1
  • PML-RARA testing for suspected acute promyelocytic leukemia 1

Risk Assessment Parameters

• Patient's age (>60 years associated with adverse prognosis) 1, 2
• Initial leukocyte count 2, 1
• AML subtype 2
• Karyotype data (favorable: t(15;17), t(8;21), inv(16)) 2, 1
• Molecular markers:
  • Favorable: mutations in C/EBPα gene and nucleophosmin gene 2
  • Adverse: FLT3 gene alterations 2

Additional Diagnostic Considerations

• Coagulation screening should be performed, particularly if morphology suggests acute promyelocytic leukemia 2
• HLA typing of patients and family members should be conducted for potential allogeneic stem cell transplantation candidates 2
• If extramedullary disease is suspected, appropriate imaging (PET/CT) should be performed 1
• For CNS signs or symptoms, evaluate using appropriate imaging (CT or MRI) 1

Common Pitfalls to Avoid

• Starting chemotherapy before obtaining satisfactory material for all diagnostic tests 1
• Relying solely on molecular genetic or FISH testing without conventional cytogenetic analysis 1
• Failing to recognize hyperleukocytosis (WBC >100,000/μL) as a medical emergency requiring immediate intervention 5

Special Considerations

• Patients with hyperleukocytosis require emergency measures including apheresis or hydroxyurea 3, 5
• Prompt institution of definitive therapy is essential for patients with high WBC counts 3
• Excessive red blood cell transfusions in patients with hyperleukocytosis can worsen symptoms by increasing blood viscosity 5