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Flashcards in Leukaemia Deck (20):
1

What is leukaemia?

A group of blood cancers where there is clonal proliferation of immature haematopoietic cells this is initiated in the bone marrow and can potentially replace normal haematopoietic events

2

What are the different types of leukaemia’s?

Acute leukaemias such as acute myeloid leukaemia and acute lymphoblastic leukaemia
And chronic leukaemias

3

How can acute myeloid leukaemia be differentiated?

There are several subtypes based on molecular changes, morphology and phenotype
It can occur at all ages but is more common in adults

4

What is acute lymphoblastic leukaemia?

This has subtypes based on morphology, lineage and molecular changes
This condition is more common in children

5

What factors may contribute to the pathogenesis of leukaemia?

There is a rare case of congenital or inherited risk factors including down syndrome or immune deficiencies
The may be a viral cause of onset such as in HTLV1 with a T-ALL subtype
Radiation exposure plays a factor
Chemical exposure to compounds such as Benzene and some chemotherapeutics may play a role

6

What are the pathological features of leukaemia?

In most cases an environmental or congenital risk factor for the disease will not be able to be observed however characteristic cytogenetic and molecular changes can be found in most cases allowing determination of leukaemogenesis, prognostic significance and therapeutic potential

7

What are the different risk groups for AML based on chromosomal translocations?

The low risk groups are t(15;17), t(8:21) and inv(16)
The intermediate risk group includes a normal karyotype and t(9;11)
High risk groups include inv (3) and a complex karyotype

8

What are the different types of molecular changes which can occur in leukaemia?

Mutations which give a proliferative advantage such as tyrosine kinase activation like bcr-abl
Mutations which block normal cell differentiation like changes to transcriptional regulators such as PML-RAR

9

What are the clinical features of acute leukaemia?

This is a condition which can occur at all ages with ALL being predominately in childhood while AML is predominately in adulthood
There are 2-3 cases per 100,000 per year

10

What are the signs and symptoms of acute leukaemia?

These are due to bone marrow failure and include anaemia (which leads to fatigue and dyspnoea), Neutropenia which can cause infection and wounds to be slow to heal, thrombocytopenia which can cause bruising and bleeding
There may be other signs which are due to organ infiltration these include
Bone pain as a result of bone marrow infiltration
An enlarged liver, spleen and/or lymph nodes
Other sites may also be enlarged including meningeal, testicular and the gums

11

How is the diagnosis of acute leukaemia made?

This is when the bone marrow biopsy is over 20% blasts
The phenotype of the cells can be used to distinguish AML from ALL
Chromosomal and molecular studies may also be useful in grouping the cancer into a subtype to provided clinically useful information

12

How effective is the current treatment for acute myeloid leukaemia?

Conventional chemotherapy treatment allows 80% of patients aged over 60 to achieve remission with 45% of these remaining remission at 5 years

13

How do each of the different risk groups in acute myeloid leukaemia respond to treatment?

The low risk group has 75% of the population remaining in remission for 5 years
The standard risk group have 45-50% of its population remaining in remission at 5 years
The poor risk group has only 25% in remission for 5 years

14

What are the features of the chronic myeloid leukaemia as a model of leukaemia biology?

This is clonal haematopoietic stem cell disorder
Median age of onset is 45-55
There are 1-2 cases per 100000 per year

15

What are the clinical features of chronic myeloid leukaemia?

This condition is mainly asymptomatic but there may be presence of splenomegaly, high leucocyte count
There may also be presence of fatigue, anorexia and weight loss

16

What is the iconic cytogenetic abnormality of chronic myeloid leukaemia?

The Philadelphia chromosome, this is the result of a reciprocal translocation between chromosome 9 and 22 leading to the pridcution of the bcr-able fusion protein with tyrosine kinase activity

17

What is the clinical course of chronic myeloid leukaemia?

There is the chronic phase which has a median of 4-6 years of stabilization
This is followed by the advanced phase of the disease which is a biphasic stage further divided into the initial accelerated phase with a median of 1 year duration which is followed by a blastic phase where the median survival is 3-6 months this is the terminal phase of the disease

18

What is the conventional therapy for chronic myeloid leukaemia?

Hydroxyurea
Interferon-alpha
Haematopoietic stem cell transplantation may also be an option with molecular remissions which cures 40-70% of patients

19

How can bcr-abl function as a therapeutic target?

This is a highly unique molecule making it a highly selective drug target
This lead to the development of glivec or imatinib mesylate
This is an inhibitor of the bcr-abl enzyme preventing its function

20

What was the IRIS study?

This examined 1106 previously untreated patients with chronic myeloid leukaemia and looked at the effect of imatinib versus interferon and cytarabine
It found that it had a complete cytogenic response of 69% compared to 7.5% and had 90% progression free survival compared to 80% at 12 months with 85% overall survival over 5 years and 93% survival from CML related deaths