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INTRODUCTION

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Epidemiology

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Epidemiology
Incidence:

18,860 (male: 11,530; female: 7,330. Estimated new cases for 2014 in the United States)

3.7 per 100,000 male and female per year (4.5 per 100,000 male, 3.1 per 100,000 female)

Deaths: Estimated 10,460 in 2014 (male: 6,010; female: 4,450)
Median age: 67 years (median age for acute promyelocytic leukemia: 40 years)
Male to female ratio: 1.48

Dores GM. Blood 2012;119:34–43

Siegel R et al. CA Cancer J Clin 2014;64:9–29

Surveillance, Epidemiology and End Results (SEER) Program, available from http://seer.cancer.gov (accessed in 2013)

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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)

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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

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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

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Risk Stratification

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Risk Stratification
Risk Status Cytogenetics Molecular Abnormalities
Better-risk

inv(16) or t(16;16)

t(8;21)

t(15;17)

normal cytogenetics

with NPM1 mutation or isolated CEBPA mutation in the absence of FLT3-ITD

Intermediate risk

normal cytogenetics

+8

t(9;11)

other nondefined

t(8;21), inv (16), t(16;16)

...

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