Acute leukaemia

Classification

Based upon the WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues (2008), classification incorporates morphologic, immunophenotypic, genetic and clinical features in an attempt to define entities that are biologically homogeneous and that have clinical relevance.

The acute leukaemias are classified as myeloid or lymphoid based on the lineage of the blast cells.Tests performed on the Bone marrow biopsy used for classification and risk stratification include:

1.     Flow cytometry

2.     Cytochemistry

3.     Cytogenetics - oncology

4.     Molecular genetics – FLT3, NPM1, CEPBalpha.

The testing of other oncogenes is becoming more common in some institutions, though their utility in risk stratification is yet to be fully defined.

Acute leukaemias are classified into three main groups:

1.     Acute myeloid leukaemia (AML) and related precursors neoplasms, which in turn comprise

a.     AML with recurrent genetic abnormalities, including AML with gene mutations (FLT3-ITD, NPM1, CEPBA)
b.     AML with myelodysplasia-related changes
c.     Therapy-related myeloid neoplasms
d.     AML, not otherwise specified
e.     Myeloid sarcoma
f.      Myeloid proliferations related to Down syndrome
g.     Blastic plasmacytoid dendritic cell neoplasm

2.     Precursor lymphoid neoplasms, which in turn cocmprise:

a.     B lymphoblastic leukaemia/lymphoma
b.     T lymphoblastic leukaemia/lymphoma

3.     Acute leukaemias of ambiguous lineage

Information of further subclassification can be found in the reference below^a

Presentation

Presenting features can include:

• Bone marrow failure (with one or more of anaemia, neutropenia and thrombocytopenia) +/- circulating blasts or leucocytosis with circulating blasts
• Bacterial / fungal infection
• Fever
• Oral ulcers
• Bruising
• DIC
• Urate nephropathy, especially in acute promyelocytic leukaemia
• Occasionally myeloid sarcoma – extramedullary collections of blasts which may present as a mass in other tissues (eg, skin etc).

All acute leukaemia cases should be treated as urgent, and discussed with and/or referred immediately to a haematology treating unit with experience in  management of these conditions.

Full blood count, Blood film. See Table 4.

Bone marrow biopsy, aspiration and trephine, for diagnosis and classification

Coagulation profile (including DIC screen in some cases) and blood chemistry (including renal and liver function) should be assessed as soon as possible.

Blood group and antibody screen and request to the hospital transfusion laboratory for modified blood products (irradiated and also CMV negative in some situations, the latter depending on local policy).

Biopsy of involved tissue for flow cytometry, immunohistochemistry, and cytogenetics if required.

HLA typing to allow identification of potential allogeneic donors may also be indicated.

^aListed in WHO classification under precursor B-cell and T-cell neoplasms.

^bListed in WHO classification under mature B-cell neoplasms.

Modified from the WHO Classification of Tumours, Pathology and Genetics: Tumours of Haematopoietic and Lymphoid Tissues 2008.