Acute Myeloblastic Leukemia

• Most common acute leukemia in adults
• Median age at diagnosis 65
• M > F

• Can arise from an underlying hematologic disorder (MDS, ET/PV)
• Consequency of prior therapy
  • Topoisomerase agents
  • Radiation
• Chemical: smoking, dry cleaning, paint
• Family/hereditary: Trisomy 21, Fanconi, ataxia telangectasia

• Marrow failure: fatigue, dyspnea, easy bleeding/bruising, infection
• Extramedullary spread
  • Lekemia cutis
  • Gingival involvement (M5 or ?myeloblastic)
  • Myeloid sarcoma
• WBC variable
• DIC in APL

• Blasts 20% in bone marrow or peripheral blood
• Cytogenic t(8, 21), inv 10, t(15,17) often with less than 20%
• Also sometimes less than 20% with myeloid sarcoma
• Auer rods not always present, but nearly pathognomonic

• FAB: M1 through M5
• AML with MDS
• AML NOS

• FLIP3
• TP53
• IDH1/IDH2

* Usually allogeneic transplant

• H&P
• ECOG
• CBC with diff, CMP, uric acid, LDH
• Coags
• BM with cytogenetics and molecular studies
• +/- CNS imaging if neuro symptoms
• +/- LP (FLIP3, TP53, M5, etc.)
• TTE/MUGA (anthrocyclines)
• MUGA
• Antimicrobials

• Induction: age, ECOG, cytogenics
  • Usually 7+3
  • Hypomethylating agent + venetoclax
    • older
    • unable to tolerate
    • complex cytogentics (TP53)
  • recheck BM in 28 days
    • Remission: less than 5% blasts
    • Consider reinduction if more than 5% blasts
      • 5+3
      • higher intensity (cytarabine, FLAG-IDA, CLAG-M)
• Consolidation
  • HIDAC 3-4 cycles
  • Liposomal cytarabine/daunorubicin 1-2 cycles
  • Hypomethylating agent + venetoclax
• Other FDA approved drugs
  • Glasdegib
  • Ivosidenib
  • Enasidenib
  • ?

• Transfusions
  • Leukodepleted
  • irradiated
• PPx
• Prompt treatment of neutropenic fever
• G-CSF/GM-CSF for septic shock: usually not given due to theoretical risk of inducing more blasts

• Highly curable
• Frequently associated with DIC with previous regimen of cytarabine and daunorubicine
• Tretinoin/Antimicrobials
  • side effect: differentiation syndrdome, treat with steroids
• Arsenic Trioxide: monitor QT
• Idarubicin? Mylotarg? For high-risk (WBC > 10)