Acute Myeloid Leukemia
An aggressive cancer of the myeloid blood cells where immature myeloblasts rapidly fill the bone marrow, causing severe anemia, infections, and bleeding.
Emergency Management: Neutropenic fever protocol: immediate blood cultures and initiation of broad-spectrum antibiotics (e.g., Cefepime or Meropenem) within 1 hour of fever spike.
Acute Myeloid Leukemia (AML) is a rapidly progressing malignant disease of the bone marrow in which hematopoietic precursors (myeloblasts) arrest in their differentiation and proliferate unchecked. This clonal expansion replaces normal marrow, leading to life-threatening bone marrow failure.
Detailed Overview
AML is the most common acute leukemia in adults. It is characterized by immense genetic and molecular heterogeneity. The leukemic myeloblasts accumulate in the marrow, leading to critical deficiencies in mature erythrocytes, granulocytes, and platelets. AML can arise de novo or secondary to antecedent hematologic disorders (like myelodysplastic syndromes) or prior leukemogenic therapies (radiation or chemotherapy). The World Health Organization (WHO) classifies AML based heavily on recurrent genetic abnormalities (e.g., t(15;17) in Acute Promyelocytic Leukemia, FLT3 mutations, NPM1 mutations), which dictate the disease's prognosis and increasingly guide targeted therapeutic strategies.
Epidemiology & Demographics
Predominantly a disease of older adults. Median age at diagnosis is 68 years. Incidence is approximately 4.3 per 100,000 adults in the US, slightly higher in men than women.
Etiological Mechanism
Most cases arise de novo with acquired somatic mutations. Known triggers include ionizing radiation, benzene exposure, prior chemotherapy (alkylators, topoisomerase II inhibitors), and progression from antecedent clonal disorders (MDS, myeloproliferative neoplasms).
Primary Causes
Acquired somatic mutations (NPM1, FLT3, IDH1/2)
Therapy-related (prior chemo/radiation)
Evolution from Myelodysplastic Syndrome (MDS)
Pathogenesis requires at least two classes of mutations. Class I mutations (e.g., FLT3-ITD, c-KIT) confer a proliferative and survival advantage to the clone. Class II mutations (e.g., RUNX1-RUNX1T1, CEBPA) impair normal myeloid differentiation. The resulting maturation block causes an accumulation of non-functional myeloblasts. These blasts expand within the bone marrow space, physically and chemically suppressing normal erythropoiesis, myelopoiesis, and megakaryopoiesis, resulting in peripheral blood cytopenias. Some blasts may invade extramedullary tissues, causing leukemic cutis or gingival hypertrophy (particularly in monocytic subtypes).
Diagnostic Criteria & Guidelines
Diagnosis requires ≥ 20% myeloblasts in the bone marrow or peripheral blood. Alternatively, the presence of specific recurrent genetic abnormalities (e.g., t(15;17), t(8;21), inv(16)) defines AML regardless of the blast percentage.
1. Standard Induction ("7+3" Regimen): Continuous IV Cytarabine 100-200 mg/m2/day for 7 days PLUS an IV Anthracycline (e.g., Daunorubicin 60-90 mg/m2/day or Idarubicin 12 mg/m2/day) for 3 days. 2. For APL (t(15;17)): All-trans retinoic acid (ATRA) 45 mg/m2/day PO divided BID plus Arsenic Trioxide 0.15 mg/kg IV daily. 3. Target additions: Midostaurin 50 mg PO BID added to 7+3 for FLT3-mutated AML.
Second-Line & Adjunctive Therapy
For older/unfit patients: Venetoclax (BCL-2 inhibitor) 400 mg PO daily + Azacitidine (hypomethylating agent) 75 mg/m2 SC/IV for 7 days every 28 days.
Surgical & Procedural Management
Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) is the definitive post-remission therapy (consolidation) for patients with intermediate or high-risk cytogenetics to provide a graft-versus-leukemia effect.
Patient Counseling & Advice
Discuss the intensive nature of the "7+3" regimen requiring a 3-4 week hospital stay. Counsel extensively on the high risk of life-threatening infections and the potential need for stem cell transplantation.
Follow-Up & Monitoring Schedule
Frequent bone marrow aspirations (typically around day 14 and day 28 post-induction) to assess for remission and measurable residual disease (MRD).
Preventive Strategies
No standard screening or prevention. Minimize occupational exposure to benzenes and unnecessary radiation.
Highly dependent on age and molecular genetics. Favorable risk (e.g., inv(16), t(8;21), isolated NPM1 mutation) has a >60% cure rate. Adverse risk (e.g., complex karyotype, TP53 mutation) has a <20% 5-year survival, heavily relying on stem cell transplant success.