Overview
Acute Myeloid Leukemia (AML) is a malignancy of the myeloid line of blood cells, characterized by the rapid growth of abnormal cells that build up in the bone marrow and blood, interfering with normal blood cell production.
Etiology & Causes
AML arises from somatic mutations in hematopoietic stem cells. While most cases are sporadic, genetic predispositions (e.g., Down syndrome), exposure to ionizing radiation, chemotherapy (t-AML), and benzene exposure are documented triggers.
Pathophysiology
The disease involves the clonal expansion of undifferentiated myeloid blasts that fail to undergo terminal differentiation. This results in bone marrow failure, causing anemia, neutropenia, and thrombocytopenia.
Epidemiology & Prevalence
Median age at diagnosis is 68 years. It accounts for approximately 1% of all cancer deaths. Males are slightly more affected than females.
Risk Factors
- Prior chemotherapy or radiation therapy
- Exposure to benzene/pesticides
- Smoking
- Genetic disorders (Fanconi anemia, Bloom syndrome)
- Myelodysplastic syndromes (MDS)
Symptoms & Warning Signs
A. Early Symptoms: Fatigue, unexplained weight loss, night sweats.
B. Common Symptoms: Pallor, bruising, petechiae, epistaxis.
C. Advanced Symptoms: Bone pain, hepatosplenomegaly, lymphadenopathy.
D. Emergency Symptoms: Hyperleukocytosis causing respiratory distress or CNS confusion (leukostasis), febrile neutropenia, disseminated intravascular coagulation (DIC).
Physical Examination Findings
Pallor (anemia), tachycardia, ecchymosis/petechiae (thrombocytopenia), gum hypertrophy (specifically in M4/M5 subtypes), and splenomegaly.
Diagnostic Evaluation
A. Clinical Assessment: Symptom history and physical exam.
B. Laboratory Testing: CBC with differential, peripheral blood smear.
C. Imaging Studies: Chest X-ray to rule out mediastinal mass.
D. Functional Tests: Cardiac ECHO (baseline for anthracyclines).
E. Biopsy Findings: Bone marrow aspirate showing >20% blasts.
F. Genetic Testing: Cytogenetics (karyotyping) and NGS for mutations (FLT3, NPM1, IDH1/2).
G. Differential Diagnosis: ALL, CML in blast crisis, myelodysplastic syndromes.
Laboratory Tests & Diagnostics
Complete Blood Count (CBC)
Type: Blood Test
Purpose: Identify cytopenias or leukocytosis.
Expected Findings: Anemia, thrombocytopenia, abnormal WBC.
Interpretation: Suggestive of marrow failure.