AML


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  • Diagnostic

    • favorable prognosis
      • t(8;21) RUNX1
      • inv16
      • NPM1
      • CEBPA
    • worse prognosis
      • c-KIT with t(8;21) and inv(16)
      • t(6;9)
      • FLT3
      • MDS cytogenetics
    • diagnostic regardless of blast count
      • t(8;21)(q22;q22); RUNX1-RUNX1T1
      • inv16
      • APML
    • morphology
      • blasts > 20%
      • Auer rods

  • Therapy & monitoring

    • During therapy
      • lack of blast reduction at day 6 of induction results in change or augmentation
      • residual blasts at the end of induction = poor prognosis
      • APML response to therapy can be maturation of promyelocytes rather than marrow ablation
    • Residual disease
      • blast >= 5%, compare with prior morphology
      • blasts without maturation, and increases on repeat biopsy
      • stains: CD34+ clusters
      • flow: aberrant (CD2, 5, 7), asynchronous, and overexpression (CD33, 34)
      • molecular, chimerism
    • Remission criteria
      • neutrophil > 1E9
      • platelet >= 100
      • blast < 5% without Auer rod
    • Shortened remission if hypercellularity, anemia, or borderline blast count(1% marrow, 3% blood)

  • Recurrent abnormalities

    • RUNX1
      • t(8;21); RUNX1-RUNXT1
      • large blasts with hof, can have large pink granules
      • neutrophil lineage
      • positive: CD34, HLADR, MPO, CD13
      • weak: CD33
    • inv16
      • eosinophils with purple granules and aberrant CAE+
      • monocytic and granulocytic differentiation
      • CD34, CD117
    • APML
      • t(15;17); PML-RARA
      • clinical: DIC, treat with ATRA
      • promyelocytes with dense Auer rods
      • types: hypergranular, microgranular (paucity of granules, bilobed nuclei, marked leukocytosis)
      • positive: CD33
      • heterogeneous: CD13
      • low/negative: HLADR, CD34, CD11a
    • MLL
      • t(9;11); MLLT3-MLL
      • can have DIC
      • monocytic (monoblasts, promonocytes)
      • positive: CD33, CD65, CD4, HLADRNSE
      • weak: CD34, CD13, CD14
      • negative: MPO
    • DEK-NUP
      • t(6;9); DEK-NUP214
      • anemia, thrombocytopenia
      • basophilia (>2%), multilineage dysplasia
    • inv3
      • can arise from prior MDS
      • giant platelets
      • monolobated/bilobated megakaryocytes, multilineage dysplasia
      • positive: CD34, HLADR, CD13, CD33, CD38
    • megakaryoblastic
      • t(1;22); RBM15-MKL1
      • megakaryoblasts
      • rare, infants and age < 3, organomegaly
      • positive: CD41, CD61
      • negative: CD34, CD45, HLADR, MPO, SBB
    • NPM1
      • myelomonocytic or monocytic features
      • female predominance, lack MDS or MPN history
      • positive: myeloid (CD13, CD33, MPO), monocytic (CD14, CD11b), CD68, NPM (cytoplasmic), C23 (nuclear)
      • negative: CD34
    • CEBPA
      • positive: CD34, HLADR, myeloid (CD13, CD33)
      • negative: monocytic (CD14, CD64)

  • AML with MDS

  • therapy related myeloid neoplasm

  • AML NOS

    • AML with minimal differentiation
      • positive: CD34, CD38, HLADR
      • negative differentiation markers: MPO, SBB, CAE, Auer rods
      • negative maturation markers: CD11b, CD15, CD14, CD64, CD65
    • AML without maturation
      • positive differentiation: myeloid (CD13, CD33, CD117), at least 3% MPO or SBB, has Auer rods
      • positive: CD34, HLADR
      • negative maturation markers: CD15, CD65, CD14, CD64
    • AML with maturation
      • positive maturation: CD13, CD33, CD65, CD11b, CD15
    • Acute myelomonocytic leukemia
      • acute = 20% blasts
      • myelo = has neutrophil lineage proliferation
      • monocytic = 20% monocytic lineage
        • monoblasts, promonocytes, monocytes
        • coexpression CD64, CD15
        • positive: NSE, CD14, CD4, CD11b, CD11c, CD64, CD36
    • Acute monoblastic and monocytic leukemia
      • 80% monocytic lineage
      • minor neutrophil component
      • monoblastic = monoblasts
      • monocytic = mostly promonocytes
    • Acute erythroid leukemia
      • erythroleukemia (erythroid and myeloid)
        • 50% erythroid, 20% of non-erythroids are myeloblasts
        • erythroid: all stages, left shifted, dysplasia (megaloblastoid, multinucleated)
        • myeloid: Auer rods, dysplasia (neutrophils, megakaryocytes)
        • hypercellular marrow
      • pure erythroid leukemia (erythroid only)
        • 80% erythroids, few myeloblasts
      • erythroblasts: MPO-, glycophorin+, hemoglobin+
      • Ddx
        • MDS: less than 20% blasts (including nonerythroids)
        • AML with MDS: 20% blast with multilineage dysplasia in 50% of cells
        • AML with increased erythroid
    • Acute megakaryoblastic leukemia
      • 20% blast, of which 50% megakaryocytic
      • megakaryoblasts: CD41+, CD61+
      • marrow replaced by megakaryocytes and blasts
    • Acute basophilic leukemia
      • blasts and immature basophils
    • Acute panmyelosis with myelofibrosis
      • panmyeloid proliferation with increased blasts
      • myelofibrosis
      • rule out AML with MDS

  • myeloid sarcoma

  • Down syndrome

  • blastic plasmacytoid dendritic cell neoplasm

  • Signout

    • Acute myeloid leukemia (*** blasts by ***)
    • Routine cytogenetic studies pending
    • Myeloid mutation panel pending
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