Concepts in malignant haematology Flashcards
What methods of testing can be used to identify normal mature haematopoietic cells ?
- Looking at the morphology of the cells e.g. blood film and blood indices
- Can also use immunophenotypying to look at Cell surface antigens to differentiate them e.g. glycophorin A = red cells
How can we identify normal progenitors/stem cells?
The main method used is immunophenotyping where Cell surface antigens (immunophenotyping) eg CD34 expressed on haematopoietic stem cells
What is malignant haematopoiesis usually characterised by ?
- Increased numbers of abnormal cells
- These abnormal cells are dysfunctional
What can dysfunctional cells in malignant haemopoiesis result in ?
Loss of normal activity of:
- Haemopoiesis (e.g. acute leukaemias)
- Immune function (e.g. certain lymphomas) – hence can get an increased susceptability associated with lymphomas
What are the potential underlying causes of malignancy?
- Increased proliferation
- Lack of differentiation
- Lack of maturation
- Lack of apoptosis
Describe the idea of driver mutations and the formation of malignant cells
Cell usually starts off with an aquired mutation then gets mutiple hits and aquires a driver mutation along the way
Driver mutation = a driver mutation is a mutation within a gene that confers a selective growth advantage
What are the 3 things that haematological malignancies are based on ?
- Based on lineage
- Based on developmental stage (precursor) within lineage
- Based on anatomical site involved
In referance to cell lineage what is the 2 main types of haematological malignancies ?
Myeloid and lymphoid malignancies
Based on anatomical site what are the 2 main types of haematological malignancies ?
Leukamias = meaning malignancy in the blood
Lymphoma = malignancy in the lymph nodes
Describe what is meant by clonality and what type are malignancies ?
the fact or condition of being genetically identical, as to a parent, sibling, or other biological source.
Normal haemopoiesis is polyclonal; malignant haemopoiesis is usually monoclonal
Polyclonal = consisting of or derived from many clones.
What are the 2 ways in which haematological malignancies can be classified dependant on the developmental stage within the lineage ?
Acute or chronic
What are the features of suggestive of a malignancy being aggressive ?
- Large cells with high nuclear-cytoplasmic ratio (big nucleus),
- prominent nucleoli (high RNA synthesis hence fast proliferation)
- rapid proliferation
Define what is meant by remission of a leukaemia ?
<5% marrow blasts with recovery of normal haemopoiesis
What are the complications of chemotherapy ?
Nausea and vomiting
Hair loss
Liver, renal dysfunction
Tumour lysis syndrome (during first course of treatment)
Infection:
- Bacterial: empirical treatment with broad spectrum antibiotics (particularly covering Gram negative organisms) as soon as neutropenic fever (IMPORTANT!)
- Fungal (if prolonged neutropenia and persisting fever unresponsive to anti-bacterial agents) (IMPORTANT!)
- Protozoal e.g PJP (more relevant in ALL therapy)
Late effects (eg loss of fertility, cardiomyopathy with anthracyclines)
What is tumour lysis syndrome and what are the symptoms of it?
When cancer cells break down and die, they release substances into the blood. If cancer cells break down so quickly that the kidneys can’t remove these substances from the blood, it can lead to tumour lysis syndrome (TLS).
- nausea
- vomiting
- diarrhea
- muscle cramps or twitches
- weakness
- numbness or tingling
- fatigue
- decreased urination
- irregular heart rate
- confusion
- restlessness
- irritability
- delirium
- hallucinations
- seizures