Revision - Leukaemia Flashcards
What cells are involved in chronic vs acute leukaemias?
Acute - uncontrolled proliferation of myeloid/lymphoid progenitor cells
Chronic - uncontrolled proliferation at a later stage of differentiation
What type of leukaemia is most commonly seen in paeds?
ALL
What genetic abnormality is seen in 90% of CML cases?
Philadelphia chromosome
What is the Philadelphia chromosome?
This results from a translocation between chromosomes 9 and 22, t(9;22).
Most common type of ALL?
B cell ALL
What is the most common childhood malignancy?
ALL
What age does ALL peak?
2-3 y/o
How much more likely are patients with Down’s syndrome likely to develop ALL & AML?
ALL - 30x more likely
AML - 150x more likely
What type of leukaemia is most associated with Down’s syndrome?
AML
What 2 viruses can predispose to leukaemia?
EBV & HIV
Clinical features of ALL?
1) Organomegaly:
- hepatomegaly
- splenomegaly
2) Fever, night sweats & weight loss
3) Lymphadenopathy
4) Thrombocytopenia:
- unusual bleeding/bruising
- petechial rash
5) Anaemia:
- pallor
- persistent fatigue
- syncope
6) Bone pain
Cause of organomegaly in ALL?
Lymphoblast infiltration of other organs leads to clinical features of organomegaly.
1st line investigation in suspected ALL?
FBC with a differential
This will highlight haematological derangements due to increased circulating lymphoblasts and bone marrow suppression
Cause of pancytopenia in ALL?
Due to bone marrow suppression (due to overproduction of one cell type)
FBC in ALL?
1) Thrombocytopenia (75%)
2) Anaemia (50%)
3) WBC can either be low (50%), high (20%), or normal if bone marrow is not yet suppressed
- differential count usually reveals neutropaenia
What does a low WBC vs high WBC count in ALL indicate?
Low WBC –> indicates that although there are lymphoblasts present they have not achieved sufficient differentiation to be recognised as WBC
High WBC –> indicates they have properties similar enough to a mature WBC to be counted.
What further investigations are required in any case presenting with suspected ALL to screen for complications?
Identifying complications:
1) Infection screen
2) Coagulation profile
3) U&Es, LDH & uric acid–> identify any metabolic abnormalities or tumour lysis syndrome.
Next investigation to diagnose ALL that is required in the presence of an abnormal FBC result?
Peripheral blood smear –> to examine circulating lymphoblasts
On a bone marrow biopsy, what is the most commonly accepted threshold for diagnosis ?
When lymphoblasts occupy >20% of bone marrow.
Give 2 red flags that would warrant an urgent specialist assessment for suspected haematological malignancy in children
1) unexplained petechiae
2) unexplained hepatosplenomegaly
Give some red flags that would warrant an urgent FBC for suspected haematological malignancy in children
1) Pallor
2) Persistent fatigue
3) Unexplained fever
4) Unexplained persistent infection
5) Generalised lymphadenopathy
6) Unexplained bruising or bleeding
7) Persistent/unexplained bone pain
What is highly suspicious for leukaemia if seen on microscopy?
Blast cells (immature cells)
What may a cogulation profile show in leukaemia?
May be deranged or show disseminated intravascular coagulation (DIC).
Why is a baseline kidney & liver function important in leukaemia?
These are needed prior to starting chemotherapy.
What may LDH & uric acid levels show in leukaemia?
Raised lactate dehydrogenase and uric acid occur with increased cell turnover.
Why is G6PD level important in leukaemia?
Treatment with rasburicase in G6PD deficiency can result in haemolytic crisis.
What is rasburicase?
Drug given before and during chemo that can help prevent tumour lysis syndrome.
What drug can help prevent tumour lysis syndrome?
Rasburicase
At the end of induction chemotherapy in leukaemia, what should the blast cell count be for patients to be classed as being in remission?
≤5%
Presence of residual disease (i.e. persistent leukaemic cells) indicates the need for more intensive chemotherapy
What are the 4 stages of chemo for ALL?
1) Induction
2) Consolidation and CNS treatment
3) Delayed intensification
4) Maintenance
What is the induction phase of chemo?
What - An intensive phase lasting 4-6 weeks.
Purpose - Aims to destroy all leukaemic blast cells.
To reduce the risk of tumour lysis syndrome in chemo for leukaemia, what can be given prior to induction?
Pre-treatment with hydration & allopurinol/rasburicase
What is the aim of the consolidation and CNS treatment stage of chemo for ALL?
Maintain remission
LP with intrathecal methotrexate aims to prevent spread to CNS
What mx is used in leukaemia to prevent CNS spread?
Intrathecal methotrexate
What is the aim of the ‘delayed intensification’ stage of chemo for ALL?
To remove as many remaining blasts as possible prior to the maintenance phase.
How long does treatment for ALL continue for in boys vs girls (i.e. the maintenance phase)?
Girls - 2y
Boys - 3y
What is tumour lysis syndrome?
As lymphoblasts lyse and release their contents, this leads to deranged metabolic abnormalities.
- hyperkalaemia
- hypocalcaemia
- hyperuricaemia
- hyperphosphataemia
Mx of tumour lysis syndrome?
Rapid rehydration with IV fluids, allopurinol and close monitoring.
Which chemo agent used in leukaemia can cause cardiotoxicity?
Anthracyclines e.g. doxorubicin
What are the clinical manifestations of tumour lysis syndrome?
1) AKI
2) Cardiac arrhythmias
3) N&V
4) Seizures
When can rasburicase be used in prophylactic management of tumour lysis syndrome?
If WCC >50
Mechanism of rasburicase vs allopurinol in tumour lysis syndrome?
Allopurinol - prevents uric acid production
Rasburicase - actively breaks down uric acid
What should always be EXCLUDED before giving rasburicase?
G6PD deficiency - as it increases the risk of haemolytic crisis.
ALL can cause organomegaly (hepatomegaly (64%) or splenomegaly (61%)).
How may this present?
- anorexia
- weight loss
- abdo pain
- abdo distension
How does lymphadenopathy typically present in ALL?
A persistent or progressive, painless, firm, rubbery lymph node.
What 2 types of leukaemias are most common in children?
ALL & AML
Peak incidence age of AML?
70+ y/o
Pathophysiology of AML?
clonal expansion of myeloid progenitor cells in the bone marrow
Clincial features of AML?
1) Fever
2) Anaemia symptoms
3) Thrombocytopenia
- Ecchymoses or petechiae.
- Gingival bleeding, epistaxis, or menorrhagia.
4) Coagulopathy
- Bleeding secondary to DIC
5) Bone pain
6) Gingival hypertrophy:
7) CNS involvement:
- Headache, visual changes, and nerve palsies.
8) Organomegaly
Onset of symptoms in AML?
There is sudden onset of symptoms and it progresses rapidly
Cuase of bone pain in leukaemia?
Due to expansion of the medullary cavity by the leukemic process.
1st & 2nd line investigations in AML?
1) FBC with differential
2) Peripheral blood smear
What will be seen on FBC with differential in AML?
- Normocytic, normochromic anaemia
- Thrombocytopenia
- Leucocyte count: maybe low, normal, or raised.
What may be seen on a peripheral blood smear in AML?
1) Raised myeloblasts
2) Auer rods
What are myeloblasts?
immature cells with large nuclei
What are auer rods?
Pink/red, rod-shaped cytoplasmic granular inclusions.
These are pathognomonic of myeloblasts.
What do auer rods indicate?
AML
What % of myeloblasts in the bone marrow confirms the diagnosis of AML?
≥20%
What is acute promyelocytic leukaemia (APL)?
a distinct subtype of AML that represents a medical emergency.
Give some complications of leukaemia
1) Tumour lysis syndrome
2) Leukostasis
3) DIC
4) Severe neutropenia
5) Severe thrombocytopenia
6) Severe anaemia
7) VTE
What is leukostasis?
Excessive number of leukaemic cells causes increased blood viscosity.
It typically presents with respiratory or neurological distress.
The clinical features are:
- Chest pain
- Headache
- Altered mental status
- Priapism
What age is associated with favourable prognosis in AML?
<50
What occurs in CLL?
due to monoclonal proliferation of B-lymphocytes.
What is the most common form of leukemia found in adults in Western countries?
CLL
Peak age of CLL?
60-70 y/o
Onset of symptoms in CLL?
Slow onset
More than 50% cases are often diagnosed coincidentally following routine blood tests.
Clinical features of CLL?
1) Symmetrical lymphadenopathy in the neck, armpits or groin
2) Hepatomegaly and/or splenomeglay
- abdo discomfort
3) Anaemia
4) Thrombocytopenia
5) Infections
What are ‘B symptoms’?
A sign that CLL may be active:
1) Frequent, severe night sweats
2) Unexplained weight loss >10% of body weight in the previous 6 months
3) High fever in the absence of any infections (>38°C)
Investigations in CLL?
1) FBC –> absolute lymphocytosis
2) Peripheral blood smear –> confirm lymphocytosis
What staging system is commonly used in the UK for CLL staging?
Binet staging system
When is chemo indicated in CLL?
should only be given to patients with active, symptomatic disease
For a small number of people, CLL can sometimes transform into a different type of cancer.
What is this referred to as?
Richter transformation
What is Richter transformation?
A serious complication of CLL and if often fatal.
It is characterised by the sudden transformation of the CLL into a significantly more aggressive form of large cell lymphoma.
Symptoms of Richter transformation?
1) a sudden and dramatic increase in the size of lymph nodes characterised by usually painless areas of swelling in the neck, axilla, abdomen (spleen) or groin.
2) a dramatic unexplained weight loss, fevers and night sweats (B-symptoms).
Patients with CLL have a higher risk of developing a secondary malignancies than the general population.
What malignancies are seen most frequently?
- melanoma
- soft tissue sarcoma
- colorectal cancer
- lung cancer
- squamous cell skin cancer
- basal cell carcinoma
Peak incidence age of CML?
60-70 y/o
What is the hallmark genetic abnormality in CML?
The presence of the BCR-ABL fusion gene.
This results from a reciprocal translocation between chromosomes 9 and 22, known as the Philadelphia chromosome.
FBC results in CML?
1) Leucocytosis
2) The differential may demonstrate increased cell numbers from the myeloid lineage of leucocytes.
3) Thrombocytosis or thrombocytopenia may occur
4) Anaemia is a common finding, often normochromic and normocytic
What is the most common treatment for CML?
Tyrosine kinase inhibitors e.g. imatinib
1st line tyrosine kinase inhibitor in CML?
imatinib
