Chapter 18: Leukemia, Acute Myeloid

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, immunophenotyping, and molecular studies (including c-KIT, FLT3-ITD, NPM, CEBPA)

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

• Cardiac scan 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)

   • APL with t(15;17)(q22;q12); PML-RARA

   • AML with t(9;11)(p22;q23); MLLT3-MLL

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

   • AML with inv(3)(q21q26.2) or t(3;3)(q21;q26.2); RPN1-EVI1

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

   • AML with mutated NPM1

   • AML with mutated CEBPA

2. AML with MDS-related features

3. Therapy-related AML

4. AML not otherwise specified

   • AML minimal with differentiation

   • AML without maturation

   • AML with maturation

   • Acute myelomonocytic leukemia

   • Acute monoblastic and monocytic leukemia

   • Acute erythroid leukemia

   • Acute megakaryoblastic leukemia

   • Acute basophilic leukemia

   • Acute panmyelosis with myelofibrosis

5. Myeloid proliferation related to Down syndrome

   • Transient abnormal myelopoiesis

   • Myeloid leukemia associated with Down syndrome

Swerdlow SH et al., eds. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues, 4th ed. Lyon, France: International Agency for Research on Cancer Press; 2008

Response Criteria for Acute Myeloid Leukemia

Morphologic leukemia-free state

Bone marrow <5% blasts in an aspirate with spicules

No blasts or Auer rods or persistence of extramedullary disease

Complete remission

Patient achieves a morphologic leukemia-free state, and

Absolute neutrophil count >1000/mm³

Platelets ≥100,000/mm³

No residual evidence of extramedullary disease

Morphologic CR–patient independent of transfusions

Cytogenetic CR–cytogenetics normal (in those with previously abnormal cytogenetics)

Molecular CR–negative molecular studies in patients with APL or Ph+ leukemia

Patients who fail to achieve a complete response are considered treatment failures

Relapse following a complete response is defined as reappearance of leukemic blasts in the peripheral blood or the finding of more than 5% blasts in the bone marrow, not attributable to another cause

Cheson BD et al. J Clin Oncol 2003;21:4642–4649

Risk Stratification