Acute Myelogenous Leukemia (AML)

Internist's overview of AML

• Pathophysiology: clonal proliferation of myeloid precursors with impaired differentiation
• Most common acute leukemia in aduts
• Diagnosis: greater than 20% blasts in periphery and bone marrow, with myeloid lineage confirmed
• Treatment options:
  • For patients younger than 60, induction with anthracycline and cytarabine is the standard of care
  • Patients older than 60 (such as our patient) are at greater risk of treatment-related complications
  • At Stanford, standard is to enroll these patients on protocol or to treat with alternative agents such as decitabine, which induces differentiation

Complications of AML

• Cytopenias
• Infection: in hematologic malignancies, pts with normal number of neutrophils may still be predisposed to infection, given infiltration of marrow with blasts
  • Febrile neutropenia
    • Definition: fever to 38.3 or to 38 sustained for one hour, with PMN count <500 or <1000 with predicted nadir of <500
    • Pathogenesis: enteric translocation, from chemotherapy-induced mucositis
      • Primarily GNRs, though specific pathogen is identified in only 30% of cases
      • Rarely anaerobes, though GPCs becoming more common with indwelling lines and instrumentation
    • Empiric therapy: should be directed at GNRs, including pseudomonas (e.g. cefepime, pip/tazo)
    • Indications for gram positive coverage (e.g. vancomycin)
      • Mucositis (for PCN-resistant oral anaerobes)
      • Hypotension
      • Skin or catheter infection
      • Hx MRSA colonization
      • Presence of GPC on gram stain
      • Hx quinolone prophylaxis
• Tumor lysis syndrome
  • Pathophysiology: results from massive tumor cell lysis with release of potassium, phosphate, nucleic acids
    • Metabolism of nucleic acids --> uric acid, which is poorly water soluble
  • Due to high metabolic demands, phosphorus concentration in malignant cells is 4x that of normal cells
  • Precipitation of uric acid and calcium phosphate in renal tubules leads to kidney injury
  • Signs and symptoms: arrhythmia, renal failure, heart failure, tetany/cramping (from hypocalcemia), seizure
  • Treatment:
    • Frequent electrolyte monitoring
    • Hydration with goal of robust urine output (100 cc/hr) to prevent crystallization
    • Allopurinol: blocks xanthine oxidase, thus reducing uric acid production
      • Does not reduce preexisting hyperuricemia
    • Rasburicase: recombinant urate oxidase to metabolize uric acid to allantoin, which is water soluble
    • Phosphate binders, kayexalate
    • Renal replacement therapy if necessary
• Leukostasis: elevated blast count with symptoms of compromised tissue perfusion
  • Pathophysiology: WBCs plug microvasculture, typically occurs with blast crisis
    • Increased viscosity (blasts less deformable)
    • Local hypoxemia from increased metabolic demands of blasts
    • Cytokine release and endothelial damage
  • Signs and symptoms: dyspnea, neuro changes, fever, tissue ischemia, DIC
  • Treatment:
    • Cytoreduction: induction chemotherapy, hydroxurea, leukapheresis, total brain irradiation
    • Supportive care: hold pRBC transfusions, as they can increase viscosity, correct thrombocytopenia to prevent reperfusion hemorrhage

(Christopher Woo MD, 12/14/10)