Leukaemia Flashcards
1
Q
What is leukaemia?
A
A cancer in the white blood cell producing cells of the bone marrow
2
Q
What are the types of leukaemia?
A
- Acute lymphoblastic leukaemia
- Acute lymphocytic leukaemia
- Acute myeloid leukaemia
- Chronic myeloid leukaemia
3
Q
What is lymphoblastic/lymphocytic mean?
A
That the abnormal cancerous cells arise from a lymphoid stem cell
4
Q
What does myeloid mean?
A
That the abnormal cancerous cell originated from a myeloid stem cell
5
Q
When should you refer a patient for immediate specialist assessment for suspicion of leukaemia?
A
If a child or young person has unexplained petechiae or hepatosplenomegaly
6
Q
In what period of time should a very urgent blood test for leukaemia be performed?
A
Within 48 hours
7
Q
When should you offer a very urgent FBC for suspicion of leukaemia in children and young people?
A
In children and young people with any of following signs and symptoms of leukaemia;
- Pallor
- Persistent fatigue
- Fever
- Persistent infection
- Generalised lymphadenopathy
- Persistent or unexplained bone pain
- Bruising
- Bleeding
8
Q
When should you offer a very urgent FBC for suspicion of leukaemia in adults?
A
As with children and young people, and also hepatosplenomegaly
9
Q
How many adults does acute lymphoblastic leukaemia affect in the UK?
A
About 800/year
10
Q
How does the incidence of ALL compare to other cancers?
A
It is the most common cancer in children and young people under the age of 35, and in older adults over 75
11
Q
How does the incidence of ALL compare between the genders?
A
It is slightly more common in males than females
12
Q
What is ALL a cancer of?
A
WBCs
13
Q
What is the mechanism of disease in ALL?
A
The process by which cells divide in an orderly and controlled way becomes out of control, and signals to stop the production of white blood cells are ignored
14
Q
Do the dividing cells in ALL mature into normal lymphocytes?
A
Many do not
15
Q
What is the result of many of the dividing cells not maturing into normal lymphocytes?
A
Too many immature blood cells (lymphoblasts) are produced
16
Q
What is the problem with the lymphoblasts in ALL?
A
They are unable to fight infection, and fill up the bone marrow so there is insufficient space to make other blood cells
17
Q
What are the types of ALL?
A
- B-lymphoblastic leukaemia
- T-lymphoblastic leukaemia
18
Q
What is the most common type of ALL?
A
B-lymphoblastic leukaemia
19
Q
Where is the typing of ALL important?
A
In determining treatment
20
Q
What is the typing of ALL based on?
A
What type of blood cell has become cancerous
21
Q
What are the risk factors for ALL?
A
- Radiation exposure
- Genetic conditions
- Exposure to chemicals
- Infection
22
Q
When can radiation exposure increase the risk of ALL?
A
When the person has been exposed to very high radiation levels, e.g. following a nuclear accident
23
Q
Why is radiation exposure not much of a concern in the UK?
A
Because very few people in the UK will have been exposed to sufficient levels of radiation to increase their risk
24
Q
Does living near a power plant increase the risk of ALL?
A
There is very little evidence for this
25
Give 2 examples of genetic conditions that increase the risk of ALL?
- Down's syndrome
| - Fanconis anaemia
26
What chemicals can increase the risk of ALL?
Industrial chemicals, e.g. benzene and other solvents
27
How is infection linked to the development of ALL?
ALL develops because of changes to certain types of immature blood cells. What causes these changes is unknown, but infection may be involved
28
Are there any specific infections that have been found to cause leukaemia?
No
29
What are the symptoms of ALL?
- Fatigue, dizziness, and palpitations
- Severe and usual bone and joint pain
- Recurrent and severe infections
- Fever without obvious infection
- LUQ fullness and early satiety
- Dyspnoea
- Headache, irritability, or altered mental status
- Haemorrhagic or thrombotic complications
30
What are the most common sites of recurrent and severe infection in ALL?
- Oral
- Throat
- Skin
- Perianal
31
What causes LUQ fullness and splenomegaly in ALL?
Splenomegaly
32
What causes dyspnoea in ALL?
Anaemia, or large mediastinal mass
33
In which kind of ALL might dyspnoea due to a large mediastinal mass present?
T-cell leukaemia
34
What causes headache, irritability, or altered mental status in ALL?
CNS involvement
35
What causes haemorrhagic or thrombotic complications in ALL?
Thrombocytopenia or DIC
36
Give 3 examples of haemorrhagic or thrombotic complications of ALL
- Menorrhagia
- Frequent nosebleeds
- Spontaneous bruising
37
What are the signs of ALL?
- Pallor
- Tachycardia and a flow murmur
- Non-specific signs of infection
- Petechiae
- Abdominal distention
- Lymphadenopathy
- Testicular enlargement
- Gum hypertrophy
- Leukaemia cutis
- Cranial nerve palsy
38
What causes petechiae in ALL?
Thrombocytopenia
39
What might petechiae progress to in ALL?
- Purpura
| - Ecchymoses
40
What causes abdominal distention in ALL?
- Hepatomegaly
| - Splenomegaly
41
What is leukaemia cutis?
google it (im on a train)
42
What are the differential diagnoses of ALL?
- Infection
- Myeloproliferative or lymphoproliferative disorders
- Myelodysplasia
- Aplastic anaemia
- Idiopathic thrombocytopenia
- Lymphoma
- Metastatic cancer
43
Give 2 examples of infections that may be differentials for ALL?
- EBV
| - Parvovirus 19
44
What investigations should be done in ALL?
- Blood tests
- Bone marrow biopsy
- Immunophenotyping
- Lumbar puncture
- General health checks
45
What blood tests should be done in ALL?
- FBC
- Blood film
- Clotting
- LDH
- Liver and renal function
46
What may be found on FBC in ALL?
- Anaemia, Hb may be below 5g/L
- Thrombocytopenia, to varying degrees
- WBC may be high, normal, or low, but there is usually neutropenia
47
What may be found on blood film in ALL?
Likely to show blast cells, but can be normal if blast cells are confined to bone marrow
48
What may be found on clotting in ALL?
DIC
49
What indicates DIC on a clotting screen?
- Elevated prothrombin time
- Reduced fibrinogen level
- Presence of fibrin degradation produces
50
What happens to LDH in ALL?
Usually raised
51
Why do you need to do liver and renal function in ALL?
Should be checked before initiating chemotherapy
52
What does the WHO classification require for a diagnosis of ALL, regarding bone marrow and/or peripheral blood?
20% or greater amount of blasts in bone marrow and/or peripheral blood
53
What is the standard procedure for obtaining a bone marrow sample in ALL?
Aspiration
54
When may core biopsy be done in ALL?
If aspiration does not yield sufficient cells
55
What is the purpose of immunophenotyping in ALL?
Helps reveal subtype
56
How can a positive confirmation of lymphoid rather than myeloid origin be achieved in ALL?
By flow cytometric demonstration of lymphoid antigens
57
Why is immunophenotyping important in ALL?
Therapeutically, it is important to differentiate between T-cell, mature B-cell, and B-cell precursor phenotypes
58
What can ALL be classified into (think ive already asked this lol)?
- B-cell ALL
| - T-cell ALL
59
What can B-cell ALL be further classified into?
- Early pre-B cell ALL
- Common ALL
- Pre-B ALL
- Mature B-cell ALL
60
What can T-cell ALL be further classified into?
- Pre-T ALL
| - Mature T-cell ALL
61
What does treatment for ALL typically consist of?
- Remission induction
- Consolidation (or intensification)
- Maintenance (or continuation) therapies
- CNS prophylaxis
- Management of relapse
62
What is the exception to the typical treatment for ALL?
Mature B-cell ALL
63
How is mature B-cell ALL managed?
Short-term intensive chemotherapy
64
What is involved in the general supportive treatment of ALL?
- Replacement therapy of blood cells
| - Antibiotic and antifungal agents
65
Why is replacement therapy of blood cells important in ALL?
Pre-existing deficiency due to ALL can be profoundly aggravated by chemotherapy
66
What is the purpose of antibiotics and antifungal treatment in ALL?
Treat opportunistic infection
67
What are the goals of induction therapy in ALL?
- Eliminate more than 99% of initial burden of leukaemic cells
- Rapidly restore normal haemopoiesis
- Restore previous performance status
68
When should treatment be started for ALL?
Immediately
69
What might be given before induction therapy in ALL?
Pre-phase therapy
70
What is given in pre-phase therapy in ALL?
Corticosteroids, either alone or in combination with a chemotherapy drug, and often with allopurinol and hydration
71
How long is pre-phase therapy given for in ALL?
5-7 days
72
What are most remission induction regimes centred on in ALL?
Multiple chemotherapy agents (vincristine, corticosteroids, and anthracycline, with or without cyclophosphamide and cytarabine)
you dont have to know the specific regime just know they give loads of chemo at once
73
How good are current treatment regimes for induction in ALL?
Achieve complete remission rates of 80-90%
74
When is maintenance therapy initiated in ALL?
Once normal haemopoiesis is achieved
75
What does maintenance therapy usually consist of in ALL?
Daily chemotherapy (6-metacaptopurine) and weekly methotrexate
76
How is 6-metacaptopurine administered?
Orally
77
What treatment duration is recommended for maintenance therapy in ALL?
2.5-3 years
78
Why is CNS prophylaxis given in ALL?
Because patients frequently have meningeal leukaemia at the time of relapse
79
What is the incidence of meningeal leukaemia in the absence of CNS prophylaxis?
50-75% in one year
80
What are the treatment modalities for CNS prophylaxis in ALL?
- CNS irradiation
- Intrathecal methotrexate
- Intrathecal triple therapy
- Systemic high-dose therapy with either methotrexate and/or cytarabine
81
What is included in intrathecal triple therapy for CNS prophylaxis in ALL?
- Methotrexate
- Steroids
- Cytarabine
82
What does stem cell transplantation allow for in ALL?
Intensification of chemotherapies and radiotherapies
83
How does stem cell transplantation allow for intensification of chemotherapies and radiotherapies?
It replaces destroyed stem cells
84
Describe the prognosis of relapse of ALL?
Very poor
85
What is the result of relapse of ALL having a very poor prognosis?
Most patients are referred for trial 'salvage' therapies
86
What are the factors predicting a good outcome after salvage therapies in ALL relapse?
- Young age
| - Short duration of first remission
87
What is the outcome of ALL related to?
The age of the patient
88
What are the cure rates of childhood ALL?
80-90%
89
What are the cure rates of ALL in elderly/frail patients?
<10%
90
What preventative strategies can be used in ALL?
There are no widely accepted preventative strategies for ALL.
Some studies suggest that breast-feeding confers protection for childhood ALL, but this remains controversial
91
What is acute myeloid leukaemia (AML)?
A malignant disease of the bone marrow
92
What happens in AML?
The precursors of blood cells are arrested in an early stage of development
93
What do most AML subtypes show, in terms of blasts?
More than 30% blasts of a myeloid lineage in blood, bone marrow, or both
94
What does the mechanism of maturation arrest in an early stage of development in AML involve?
The activation of abnormal genes through chromosomal translocations and other genetic abnormalities
95
What is the effect of the maturation arrest in an early stage of development in AML?
Reduces the normal blood cells
96
What does failure of apoptosis in AML lead to?
Accumulation in various organs, especially the liver and spleen
97
How common is AML, compared to other leukaemias?
It is the most common leukaemia in adults
98
At what age does AML occur?
It can occur at any age, but the incidence increases with age, and the median age of onset is 67
99
What are the subtypes of AML?
- AML with characteristic genetic abnormalities
- AML with multi-lineage dysplasia
- AML and MDS, therapy related
- AML not otherwise categorised
100
Who does the subtype of AML with multi-lineage dysplasia include?
Patients who have had prior myelodysplastic syndrome (MDS) or myeloproliferative disease that transforms into AML
101
What does the subtype of AML and MDS, therapy related include?
Patients who had had prior chemotherapy and/or radiation
102
What are the risk factors for AML?
- Other haematological disorders
- Radiation
- Congenital disorders
- Exposure to benzene
- Survivors of cancer chemotherapy
103
What other haematological disorders increase the risk of AML?
- Myelodysplastic syndrome
- Aplastic anaemia
- Myelofibrosis
104
What congenital disorders increase the risk of AML?
- Bloom's syndrome
- Down's syndrome
- Fanconi's anaemia
- Neurofibromatosis
105
What is the presentation of AML related to?
Bone marrow failure or organ infiltration
106
How does the presentation of AML differ between children and older people?
Children or young adults may present with acute symptoms over a few days to weeks, whereas older people may present with fatigue over weeks or months
107
What are the symptoms of AML?
- Dizziness and shortness of breath on exertion
- Fever
- Early satiety and fullness in LUQ
- Bone pain
108
What feature of the fever may be present with AML?
Failure to respond to antibiotics
is that a feature? idk
109
What causes the early satiety and fullness in LUQ in AML?
Splenomegaly
110
What are the emergency presentations of AML?
- Haemorrhage into lungs, GI tract, or CNS
| - Leukostasis
111
What cause leukostasis in AML?
Extremely high WBC
112
What are the most common sites for infiltration of AML?
- Liver
- Spleen
- Gums
113
Why is knowing the most common sites of infiltration of AML clinically important?
Should look for signs in those locations
114
What examination features may be present in AML?
- Pallor
- Signs of infection, e.g. fever, pneumonia
- Hepatomegaly and splenomegaly
- Petechiae on lower limbs
- Gingivitis, with swollen, bleeding gums
115
What does the diagnosis of AML require?
The examination of peripheral blood and bone marrow specimens
116
What tests are done on the peripheral blood and bone marrow specimens in AML?
- Morphology
- Cytochemistry
- Immunophenotyping
- Cytogenetics
- Molecular genetics
117
What investigations are done in AML?
- Blood testing
- Bone marrow aspiration
- Allotyping
- Cytochemical testing
118
What blood tests should be done in AML?
- FBC
- Clotting screen
- LDH
- Liver and renal function
119
What may be found on FBC in AML?
- Variable degree of anaemia and thrombocytopenia
- Total WBC may be normal, high, or low, and sometimes extremely high
- Neutrophils usually depleted
120
What condition is commonly found on clotting screen in AML?
DIC
121
What findings on clotting screen are suggestive of DIC?
- Prolonged thrombin time
- Low level of fibrinogen
- Fibrin degradation products
122
What happens to LDH in AML?
Usually raised
123
Why do you need to check liver and renal function in AML?
Must be checked before initiating chemotherapy
124
What is the importance of bone marrow aspiration in AML?
It is the diagnostic procedure
125
What findings on bone marrow aspiration are required for a diagnosis of AML?
More than 20% blasts in the peripheral blood
126
Who should be HLA typed at diagnosis of AML?
Patients potentially suitable for allogenic stem cell transplantation, and their first-degree family members
127
What is the purpose of cytochemical staining in AML?
It allows for classification of AML into its subtypes
128
What can cytogenetic studies provide in AML?
Important information about prognosis
129
What is the usually accepted criteria of therapeutic response in AML?
- Blast clearance in the bone marrow to <5% of all nucleated cells
- Morphologically normal haematopoiesis
- Return of peripheral blood cell counts to normal levels
130
Where is treatment for AML co-ordinated?
Specialist centres
131
On what basis is AML treatment delivered?
Two phases
132
What are the phases of AML treatment?
- Induction
| - Post-remission consolidation (intensification)
133
Is stem cell transplantation an option in AML?
Yes
134
What are the other aspects of care in AML?
- Blood product replacement
- Antibiotics for infection
- Allopurinol to reduce uric acid levels
135
What might patients with excessive leukocytosis require before commencing chemotherapy for AML?
Emergency leukophoresis
136
What is the prognosis of AML dependant on?
- Age
- Cell type
- Burden of disease
- Pre-existing medical conditions
137
What social factor affects the prognosis of AML?
Prognosis is worse with socio-economic deprivation
138
What % of people with AML develop secondary malignancies?
13%
139
What rates of complete remission can be achieved in younger patients?
80%
140
What is the 5-year survival of AML in younger patients?
40%
141
What are the remission rates of AML in over 60's?
60%
142
What is the limitation of remission in over 60's?
Remissions are usually transient
143
What is the median survival of AML in over 60's?
5-10 months
144
What pre-existing medical conditions are associated with a poorer prognosis from AML?
- Diabetes
- CHD
- COPD
145
What is chronic lymphocytic leukaemia?
A monoclonal expansion of B-lymphocytes with accumulation of abnormal lymphocytes
146
Where do abnormal lymphocytes accumulate in chronic lymphocytic leukaemia?
- Blood
- Bone marrow
- Spleen
- Lymph nodes
- Liver
147
How do the lymphocytes in CLL appear morphologically?
Normal
148
What is abnormal about the lymphocytes in CLL?
They are immature and non-reactive
149
What is the result of the lymphocytes being immature and non-reactive in CLL?
Results in immunological compromise
150
How common is CLL compared to other leukaemias?
It represents about 1/4 of all leukaemias seen in clinical practice
151
When does CLL present?
It is largely a disease of older people
152
What causes CLL?
Unknown
153
What are the known risk factors for CLL?
- Age
| - Radiation exposure
154
Are people in the UK exposed to radiation levels high enough to increase the risk of CLL?
No, it occurs after nuclear accidents etc
155
Describe the presentation of CLL?
Variable, with insidious onset
156
Are most people symptomatic at presentation of CLL?
No
157
How are people diagnosed with CLL asymptomatically?
Following routine blood tests
158
What are the symptoms of CLL?
- Susceptibility to infection
- Symmetrically enlarged lymph nodes
- Abdominal discomfort from an enlarged spleen
- Bleeding or petechiae in skin or mucous membranes
