Concepts in Malignant Haematology Flashcards
What properties do normal haematopoietic stem cells have?
- self-renew
- proliferation
- differentiation (commit to certain lineage)
- maturation
- apoptosis
How can mature myeloid (i.e. non-lymphoid) cells be identified?
- Morphology
- Cell surface antigens (glycophorin A = red cells)
- Enzyme expression (myeloperoxidase = neutrophils)
How can we tell progenitor/ stem cells apart?
Immunophenotyping
=> cell surface antigens (CD20/ CD3)
What is malignant haematopoiesis?
an increase in abnormal or dysfunctional cells
loss of normal activity
(i.e. in leukaemia, there is loss of haemopoiesis; In lymphoma, there is loss of immune function)
Which of the properties of haematopoietic stem cells are altered during malignant haematopoiesis?
- increased proliferation BUT decreased: - differentiation - maturation - apoptosis
Describe what happens in an acute leukaemia
- proliferation of progenitors
- block in differentiation/ maturation
=> lots of common myeloid precursors in the bone marrow
What happens in chronic myeloid leukaemia?
- proliferation of abnormal progenitors
- no differentiation/ maturation block so some mature cells are still formed
What are the potential causes of haematological malignancy?
- somatic mutations in oncogenes or tumour suppressors (driver or passenger mutations)
- multiple genetic “hits” needed
- recurrent cytogenetic abnormalities (deletion/abnormal chromosomes)
What is the difference between driver and passenger mutations?
DRIVER = cause of cancer PASSENGER = causes genetic instability
Cells with a driver mutation are more likely to survive and keep dividing. TRUE/FALSE?
TRUE
What screening test performed as a child can be looked at retrospectively to diagnose Acute Lymphoblastic Leukaemia?
Guthrie Heel Prick Testing a few days after birth
How are types of haematological malignancies classified?
Based on:
- lineage
- developmental stage within lineage
=> e.g. Acute Leukaemia = no mature cells produced
=> Chronic Leukaemia = mature cells still produced - anatomical site
=> Blood = leukaemia
=> Lymph Node = Lymphoma
How do acute leukaemias appear histologically and clinically?
HISTOLOGY:
- large cells
- high nuclear:cytoplasm ratio
- rapid proliferation
CLINICAL:
- rapid progression of symptoms
- pancytopenia common
What is the definition of acute leukaemia?
> 20% blasts in peripheral blood or bone marrow
Acute Lymphoblastic Leukaemia (ALL) is common in what age group?
Childhood
What symptoms usually present in ALL?
- marrow failure
=> anaemia
=> infections
=> bleeding - high blast count causes obstruction of circulation
- extra-medullary sites can be affected
- bone pain
Acute Myeloid Leukaemia (AML) is more common in what age group?
Elderly (>60s)
Why does AML usually occur?
- De novo mutation
OR secondary to having Chronic Myeloid Leukaemia (CML)
How do patients usually present with AML?
- similar to ALL
- marrow failure and consequences
- some sub-groups (e.g. Promyelocytic AML) have characteristic appearance e.g. DIC
How are both types of Acute Leukaemia investigated?
- Blood count/ film
- Coag. screen
What does a blood film show in acute leukaemia?
- decrease in normal cells
- abnormal cells present (BLASTS)
=> high nuclear:cytoplasmic ratio
=> Auer’s Rods also present in AML
What is a bone marrow aspirate used for in Acute Leukaemia?
- check morphology of cells
- immunophenotype to check lineage
=> differentiates between AML and ALL - analyse genetics for prognosis
When would a Trephine biopsy be used in acute leukaemia?
if aspirate sub-optimal
OR to assess morphology better
What is the CURATIVE treatment for acute leukaemias?
ALL - 2-3 years of multi agent chemo
AML - intensive chemotherapy (2-4 cycles)
- 5-10 days of chemo then 2-4 weeks recovery
- prolonged stay in hospital usually req’d
HOw do patients with leukaemia usually have their chemotherapy delivered?
Via a central venous catheter
e.g. Hickmann line
What problems can occur due to suppression of the bone marrow by chemotherapy?
- anaemia
- neutropenia (increased infection risk)
- thrombocytopenia (increased bleeding risk)
What are the main complications of chemotherapy?
- Nausea and vomiting
- hair loss (alopecia)
- liver/ renal dysfunction
- bacterial infection
- fungal infection if prolonged neutropenia and fever
What are the late complications of chemotherapy?
- loss of fertility
- cardiomyopathy
What is considered complete remission in leukaemia?
<5% blasts in blood
return of normal haemopoiesis
Do patients with leukaemia usually recover?
Childhood ALL - many get remission
Adult ALL - 30-40% achieve remission
Elderly AML (>60yrs) - many don’t recover
What treatments other than chemotherapy are available for patients with leukaemia?
Targeted Tx: e.g. can target Philadelphia Chromosome
Allogenic stem cell transplant
