Hematology Oncology · Year 2 · from Hematology Oncology

Case 1: Acute Myeloid Leukemia (AML)

Patient Presentation

Demographics: 62-year-old male

Chief Complaint: Progressive fatigue, easy bruising, and fever for 2 weeks

History of Present Illness: The patient reports gradually worsening fatigue limiting his daily activities over the past month. He noticed easy bruising on his arms and legs, and bleeding from his gums when brushing teeth. He has had low-grade fevers for 2 weeks without clear source. He also reports mild bone pain in his legs and back. He has no significant past medical history and takes no medications.

Physical Examination:

  • Vital signs: BP 110/68, HR 102, RR 18, Temp 38.2C
  • General: Pale, fatigued-appearing man
  • HEENT: Gingival hyperplasia with bleeding, pallor
  • Lymph nodes: No lymphadenopathy
  • Cardiac: Tachycardic, flow murmur
  • Lungs: Clear
  • Abdomen: Mild hepatomegaly, no splenomegaly
  • Skin: Multiple ecchymoses, petechiae on lower extremities
  • Neurologic: Normal

Workup and Results

Complete Blood Count:

  • WBC: 68,000/uL
  • Differential: 78% blasts
  • Hemoglobin: 7.2 g/dL (severe anemia)
  • Platelets: 18,000/uL (severe thrombocytopenia)

Peripheral Blood Smear:

  • Numerous large blasts with high N:C ratio
  • Fine chromatin, prominent nucleoli
  • Some blasts contain Auer rods
  • Occasional blasts with cytoplasmic granules

Bone Marrow Biopsy:

  • 82% blasts
  • Auer rods identified
  • Flow cytometry: CD34+, CD13+, CD33+, CD117+, MPO+, HLA-DR+

Cytogenetics and Molecular:

  • Normal karyotype
  • NPM1 mutation: Positive
  • FLT3-ITD: Negative
  • IDH1/2: Negative

Chemistry:

  • LDH: 850 U/L (elevated)
  • Uric acid: 9.2 mg/dL (elevated)
  • Creatinine: 1.3 mg/dL

Clinical Image

Peripheral blood smear demonstrating myeloblasts with Auer rods, pathognomonic crystallized azurophilic granules confirming myeloid lineage in acute myeloid leukemia.

Diagnosis

Acute Myeloid Leukemia, NPM1-Mutated (Favorable Risk)

Diagnostic criteria:

  • ≥20% blasts in bone marrow
  • Myeloid lineage confirmed by Auer rods and immunophenotype (CD13+, CD33+, MPO+)
  • NPM1 mutation without FLT3-ITD = favorable risk category

Treatment Plan

  1. Pre-treatment management:
  • TLS prophylaxis: IV fluids, allopurinol
  • Transfusion support: PRBCs for anemia, platelets to maintain >10,000/uL
  • Infection workup and empiric antibiotics for fever
  1. Induction chemotherapy:
  • 7+3 regimen: Cytarabine 100-200 mg/m2 continuous infusion x 7 days + Daunorubicin 60-90 mg/m2 x 3 days
  • Add midostaurin if FLT3 mutated
  1. Post-induction:
  • Day 14 bone marrow to assess response
  • Day 28 bone marrow for CR assessment
  • Anticipate 3-4 weeks of pancytopenia
  1. Consolidation (if CR achieved):
  • High-dose cytarabine (HiDAC) x 3-4 cycles
  • Given favorable risk (NPM1+ without FLT3-ITD), transplant not required in CR1
  1. Supportive care:
  • G-CSF may be used post-chemotherapy
  • Antimicrobial prophylaxis during neutropenia

Teaching Points

  1. AML is defined by ≥20% myeloid blasts in bone marrow or blood
  2. Auer rods are pathognomonic for myeloid lineage and confirm AML over ALL
  3. Risk stratification by cytogenetics/molecular profile is critical for treatment decisions
  4. NPM1 mutation without FLT3-ITD is favorable risk with ~60-70% cure rate with chemotherapy alone
  5. The 7+3 regimen has been standard induction for decades
  6. Gingival hyperplasia suggests monocytic differentiation (M4/M5 subtypes)
  7. Tumor lysis syndrome prevention is essential given high blast count

All cases for this lecture as Markdown