Clinical Scorecard: Acute Myeloid Leukemia: An In-Depth Review and Update for 2016

At a Glance

Key Highlights

• AML accounts for approximately 80% of acute leukemias in adults with an incidence of 3-5 per 100,000 in the US.
• Pathogenesis involves a two-hit model: class I mutations activating proliferation and class II mutations impairing differentiation, often with additional epigenetic gene mutations.
• Diagnosis requires ≥20% blasts in bone marrow or blood, confirmed by myeloid markers, cytogenetics, or molecular abnormalities; WHO classification integrates genetic and clinical features.

Guideline-Based Recommendations

Diagnosis

• Establish AML diagnosis with ≥20% blasts in bone marrow or peripheral blood.
• Confirm myeloid origin via myeloperoxidase activity, immunophenotyping, or Auer rods presence.
• Use cytogenetic and molecular testing to identify recurrent genetic abnormalities (e.g., t(8;21), t(15;17), inv(16)) and mutations (NPM1, CEBPA, FLT3).
• Apply WHO classification incorporating morphology, immunophenotype, genetics, and clinical presentation.

Management

• Consider patient age and genetic risk factors in treatment planning.
• Recognize poor prognosis in elderly patients despite advances; tailor therapy accordingly.
• Monitor for therapy-related AML in patients with prior exposure to topoisomerase II inhibitors, alkylating agents, or radiation.

Monitoring & Follow-up

• Regularly assess blast counts and hematologic parameters to evaluate treatment response.
• Monitor for molecular markers such as FLT3-ITD and NPM1 mutations to guide prognosis and therapy.
• Observe for complications related to bone marrow failure including infection and bleeding.

Risks

• High mortality within 1 year in patients aged 65 years or older (~70%).
• Risk of therapy-related AML following prior cytotoxic treatments.
• Poor prognosis associated with STAT3 phosphorylation and certain mutations (e.g., FLT3-ITD).

Patient & Prescribing Data

Adult AML patients, with special consideration for elderly patients and those with therapy-related AML

Genetic and molecular profiling informs prognosis and therapeutic decisions; elderly patients have poorer outcomes despite current treatments.

Clinical Best Practices

• Incorporate comprehensive genetic and molecular testing at diagnosis to classify AML subtype and guide treatment.
• Use WHO 2016 classification for precise AML diagnosis integrating clinical, morphological, and genetic data.
• Recognize the heterogeneity of AML and tailor management based on patient age, genetic mutations, and disease subtype.

References

• American Cancer Society AML Facts & Figures 2015
• WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues, 2016