Chapter 2: Acute Myeloid Leukemia

Epidemiology

Work-up

• H&P

• CBC and leukocyte differential counts, platelets, electrolytes, liver function tests, PT, PTT, INR, fibrinogen, LDH, uric acid

• Bone marrow biopsy with cytogenetics (karyotype and FISH), immunophenotyping, and molecular studies (including c-KIT, FLT3 [ITD and TDK], NPM1, CEBPA [biallelic], IDH1, IDH2, TP53)

• HLA typing for patients who are candidates for allogeneic hematopoietic stem cell transplantation

• Chest x-ray and CT/MRI scans if clinically indicated to rule out infection or myeloid sarcoma

• Echocardiogram if therapy with anthracycline is planned, especially if prior cardiac history or prior anthracycline use

• Lumbar puncture if neurologic symptoms (LP should be performed if a mass/lesion is not detected on imaging studies)

Pathology

WHO Classification of Acute Myeloid Leukemia

1. AML with recurrent genetic abnormalities

   • AML with t(8;21)(q22;q22) (RUNX1-RUNX1T1)

   • AML with inv(16)(p13.1q22) or t(16;16)(p13.1;q22) (CBFB-MYH11)

   • Acute promyelocytic leukemia with PML-RARA

   • AML with t(9;11)(p21.3;q23.3); MLLT3-KMT2A

   • AML with t(6;9)(p23;q34.1); DEK-NUP214

   • AML with inv(3)(q21q26.2) or t(3;3)(q21.3;q26.2); GATA2, MECOM (EVI1)

   • AML (megakaryoblastic) with t(1;22)(p13.3;q13.3); RBM15-MKL1

   • Provisional entity: AML with BCR-ABL1

   • AML with mutated NPM1

   • AML with biallelic mutations of CEBPA

   • Provision entity: AML with mutated RUNX1

2. AML with MDS-related changes

3. Therapy-related myeloid neoplasms

4. AML not otherwise specified

   • AML minimal with differentiation

   • AML without maturation

   • AML with maturation

   • Acute myelomonocytic leukemia

   • Acute monoblastic/monocytic leukemia

   • Pure erythroid leukemia

   • Acute megakaryoblastic leukemia

   • Acute basophilic leukemia

   • Acute panmyelosis with myelofibrosis

5. Myeloid sarcoma

6. Myeloid proliferation related to Down syndrome

   • Transient abnormal myelopoiesis (TAM)

   • Myeloid leukemia associated with Down syndrome

Blastic plasmacytoid dendritic cell neoplasms

Acute leukemias of ambiguous lineage

• Acute undifferentiated leukemia

• Mixed phenotype acute leukemia with t(9;22)(q34.1;q11.2); BCR-ABL1

• Mixed phenotype acute leukemia with t(v;11q23.3); KMT2A rearranged

• Mixed phenotype acute leukemia, B/myeloid, not otherwise specified

• Mixed phenotype acute leukemia, T/myeloid, not otherwise specified

Myeloid neoplasms with germ-line predisposition without a pre-existing disorder or organ dysfunction

• AML with germ line CEBPA mutation

• Myeloid neoplasms with germ line DDX41 mutation

Myeloid neoplasms with germ line predisposition and pre-existing platelet disorders

• Myeloid neoplasms with germ line RUNX1 mutation

• Myeloid neoplasms with germ line ANKRD26 mutation

• Myeloid neoplasms with germ line ETV6 mutation

Myeloid neoplasms with germ line predisposition and other organ dysfunction

• Myeloid neoplasms with germ line GATA2 mutation

• Myeloid neoplasms associated with bone marrow failure syndromes

• Juvenile myelomonocytic leukemia associated with neurofibromatosis, Noonan syndrome, or Noonan syndrome–like disorders

• Myeloid neoplasms associated with Noonan syndrome

• Myeloid neoplasms associated with Down syndrome

Arber DA et al. Acute myeloid leukaemia with recurrent genetic abnormalities. In: Swerdlow S et al. editors. ...