0326 - Acute Leukaemia Flashcards
What is leukaemia?
A disease of the blood, not the tissues.
A spectrum of diseases resulting from a malignant neoplastic proliferation of heamopoietic or lymphoid cells. It results from an acquired mutation in a single stem cell, the progeny of which form a clone of leukaemic cells. Most often, a series of genetic alterations, rather than a single event, is required to give rise to a clinical disease.
What is acute leukaemia?
A RAPID neoplastic proliferation of relatively primitive (undifferentiated) haemopoietic or lymphoid cells. The leukaemic cells lack functional characteristics and the clinical disease resulting is aggressive and rapidly progressive. Weeks-months if untreated.
What are the three types of acute leukaemia.
Acute myeloid leukaemia
Acute lymphoid leukaemia
Undifferentiated, biphenotypic leukaemia (rare)
What is the epidemiology of AML?
Most common leukaemia in adults, 3-5 cases per 100,000.
Median age at diagnosis = 65yrs
M:F 5:3
What is the epidemiology of ALL?
Highest incidence in childhood - children, teenagers, and young adults. 1 in 100,000.
M:F similar
What are the two most important clinical features of acute leukaemia? How do they manifest?
Bone Marrow Failure - Accelerated haemopoiesis and maturational arrest, with the leukaemic clone proliferating at the expense of normal haemopoiesis.
Extramedullary infiltration - Eventually, bone medulla runs out of space, with the cell clone moving to spleen and liver.
What are three clinical features of bone marrow failure? How do they manifest?
- Leukopenia - Fever and infection (including opportunistic), mouth ulcers.
- Thrombocytopenia - Bleeding (epistaxis, gums, haemoptysis, cerebral), ecchymoses (>1cm subcutaneous bleed), petechiae (
What are some clinical features of extramedullary infiltration?
Hepatosplenomegaly and lymphadenopathy Gingival Hyperplasia (rare) Spinal cord compression/paraparesis Headache and seizures (CNS) Nerve palsies Skin rashes/infiltration Bone pain.
What is a sanctuary site? What is its relevance in leukaemia?
An area of the body that is protected by homeostasis/different blood flow (testes, eyes, CNS).
Relatively protected from the effects of systemic chemotherapy so may require particular targeting.
Testicular involvement in ALL is not uncommon.
How is Leukaemia classified (name) what are two benefits of this system?
WHO Classification of Neoplasms in the Haemopoietic System (2008)
Reflects the greater understanding of the molecular basis of leukaemia
Incorporates both disease behaviour and treatment response.
What factors does Leukaemia classification take into account?
Morphology of cells Immunophenotyping pattern Cytogenetics Molecular testing Disease behaviour and treatment response.
Why is molecular and cytogenetics important in leukaemia?
Many mutations can give a similar leukaemia.
Knowing the mutation allows tailored prognosis and treatment, increasing the likelihood of a positive response.
Good to know it at diagnosis.
What is the single most important blood result for diagnosing acute leukaemia?
Presence of blasts in the blood. Even in severe infection you should only have 0-1 blast in the sample - should make you very suspicious.
What changes would you see on bone marrow biopsy in leukaemia?
Complete loss of normal architecture and fat cells - Deep blue instead of light pink due to leukaemic nuclei.
How can immunophenotyping help diagnose leukaemia?
Used to distinguish between ALL/AML/Mixed
Uses labelled monoclonal antibodies to detect (CD) antigens on cells. These are fed through a flow cytometer/cell sorter.
Patterns of CD antigen expression are used to classify the leukaemia.
