3.1 Specialist diagnostic work-up

3.1 Specialist diagnostic work-up

The treatment team, after taking a thorough medical history and making a thorough medical examination of the patient, should undertake the following investigations under the guidance of a specialist.

Diagnostic evaluation is required for two complementary purposes – first, to establish a precise diagnosis according to the most recent classification system, and second, to assess the presence and management of comorbidities and the patient’s fitness because these affect both response to treatment and toxicity from treatment.

To achieve this, the treatment team should:

  • perform a thorough physical examination, including assessing for the presence of extramedullary disease (e.g. leukaemia cutis, gum infiltration and/or central nervous system symptoms)
  • undertake the following investigations under the guidance of a specialist:
  • peripheral blood tests
  • bone marrow aspirate (BMA)
  • trephine biopsy +/- lumbar puncture, imaging or tissue biopsy when extramedullary disease is suspected.

Note: Details of specific tests appear below in section 3.2.

Pathology specimens should be collected and reviewed by a pathologist with expertise in diagnosing AML, before a treatment plan is instituted.

Where safe and timely to do so, it is preferable that the diagnostic blood tests and bone marrow biopsy are performed at the specialist treatment centre. This will facilitate review of blood and bone marrow results by the specialist management team and ensure all necessary tests are conducted.

Morphological assessment to identify APL should be conducted immediately and the result conveyed to the treating physician as soon as possible.

For all patients with AML, other results necessary for immediate management decisions should be available within 72 hours of the patient presenting.

Specialised testing is performed to:

  • ensure accurate diagnoses
  • accurately sub-classify AML
  • inform prognosis
  • inform treatment decisions that are evidence-based.

Classification is the principle process by which key information is collated to inform prognosis and management of patients with AML.

Classification and risk stratification for AML involves these tests:

  • morphological assessment
  • cytogenetics
  • flow cytometry
  • molecular pathology (genetic testing).

AML is classified according to the World Health Organization’s classification of AML tumours (Arber et al. 2016). The European LeukemiaNet stratification system classifies patients as having favourable, intermediate and adverse risk based on karyotype, selected molecular abnormalities (currently FLT3, NPM1, TP53, ASXL1, RUNX1 and CEBPA mutation status) (Döhner et al. 2017).

The other most important prognostic features are age at diagnosis, performance status, presence of extramedullary disease, hyperleukocytosis, therapy-related AML (previous exposure to cytotoxics), presence of an antecedent bone marrow failure syndrome and response to induction chemotherapy.

Newer molecular markers with prognostic and therapeutic relevance in AML are likely to become clinically routine in the near future (Grimwade et al. 2016).

Most genetic abnormalities in AML only occur in abnormal blood cells and are not related to genetic abnormalities that affect the whole body and/or are inherited. However, heritable genetic abnormalities may be identifiable in a very small number of patients. AML with a genetic predisposition is an entity in the World Health Organization classification, and most diagnostic centres have access to identification of heritable genetic abnormalities related to leukaemia. This becomes significantly relevant if a family member is being considered as a stem cell donor.