Canterbury DHB

Laboratory Diagnosis

The diagnosis is established by the laboratory investigations outlined below:

• Morphology of blood and marrow.
• Immunophenotyping.
• Cytogenetics.
• Molecular analysis.

Integration of the above findings leads to the precise diagnosis being established. We are currently using the WHO 2016 Classification. When all the laboratory tests have been completed, the laboratory sends out a Summary of Laboratory Findings report.

Morphology of Blood and Bone Marrow

The blood changes are quite variable but usually show a normocytic anaemia, neutropenia, and thrombocytopenia. The proportion of blast cells in the blood ranges from barely detectable to 300–400 x10⁹/L. A bone marrow is usually performed in order to establish the diagnosis and to carry out the further tests listed below. If the blast count is very high a bone marrow may not be required. In AML the blast cells are myeloblasts, and in general more than 20% need to be present in the bone marrow to establish a diagnosis of acute leukaemia.

Immunophenotyping

The primitive leukaemic cells carry antigens on their surface/cytoplasm that indicate a myeloid origin in patients with AML. These may be stem cell antigens (CD34), myeloid antigens (CDs 117,13,33), monocytic antigens (CD14). Rarely, erythroid (Glycophorin A) or megakaryocyte (CDs 42b or 61) markers may be present. On occasion, markers ordinarily found on lymphoid cells may be detected (e.g., CD2) and this aberrant phenotype may be useful in residual disease monitoring. Biphenotypic (lymphoid and myeloid) acute leukaemias do occur, but are rare.

For a full account of immunophenotyping in AML, refer to the WHO Classification of Tumours - Pathology and Genetics of Tumours of Haemopoietic and Lymphoid Tissues, 2016.

Minimal residual disease monitoring by flow is offered by LabPlus in Auckland.

Cytogenetics

Cytogenetic changes in AML leukaemic cells are common and many of these may have therapeutic or prognostic significance. 2017 ELN risk stratification categorise AML into favourable, intermediate and adverse groups based on the presence of cytogenetic and other genetic changes (see table below).

DNA Analysis

DNA analysis is essential for any patient who will receive intensive treatment and will define what DNA change may underlie the cytogenetic abnormalities observed on karyotype. Local assays that are offered include FLT3-ITD and NPM1 as well as a myeloid NGS panel covering many of the most commonly encountered genetic changes.

Table sourced from "Acute myeloid leukemia: 2019 update on risk-stratification and management" American Journal of Hematology. 2018;93: 1267-1291 with permission of Wiley and Sons.

The Decision to Treat

• The decision with regard to both initial and subsequent treatments may be quite complex. The patient and family need to be fully informed. The factors to be considered before initial intensive treatment is given include the patient’s age, co-morbidities, performance status, and the patient’s wishes.
• Patients who are older but still fit enough to receive intravenous therapy that is inevitably associated with the long period of cytopenias and significant complications are usually offered a DA 3+8 or 3+10 regimen.
• These patients require the investigations below. Non-intensively treated patients require less extensive initial investigations.
• If initial intensive treatment is not deemed appropriate then it may be appropriate to offer them low dose cytarabine, or hydroxyurea along with full supportive care. The Palliative Care Team should be involved at an early stage for these patients.

Topic Code: 4274