Acute Lymphoblastic Leukaemia Flashcards
What is leukaemia?
A cancer in the white blood cell producing cells of the bone marrow
What are the types of leukaemia?
- Acute lymphoblastic leukaemia
- Acute lymphocytic leukaemia
- Acute myeloid leukaemia
- Chronic myeloid leukaemia
What is lymphoblastic/lymphocytic mean?
That the abnormal cancerous cells arise from a lymphoid stem cell
What does myeloid mean?
That the abnormal cancerous cell originated from a myeloid stem cell
When should you refer a patient for immediate specialist assessment for suspicion of leukaemia?
If a child or young person has unexplained petechiae or hepatosplenomegaly
In what period of time should a very urgent blood test for leukaemia be performed?
Within 48 hours
When should you offer a very urgent FBC for suspicion of leukaemia in children and young people?
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
When should you offer a very urgent FBC for suspicion of leukaemia in adults?
As with children and young people, and also hepatosplenomegaly
How many adults does acute lymphoblastic leukaemia affect in the UK?
About 800/year
How does the incidence of ALL compare to other cancers?
It is the most common cancer in children and young people under the age of 35, and in older adults over 75
How does the incidence of ALL compare between the genders?
It is slightly more common in males than females
What is ALL a cancer of?
WBCs
What is the mechanism of disease in ALL?
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
Do the dividing cells in ALL mature into normal lymphocytes?
Many do not
What is the result of many of the dividing cells not maturing into normal lymphocytes?
Too many immature blood cells (lymphoblasts) are produced
What is the problem with the lymphoblasts in ALL?
They are unable to fight infection, and fill up the bone marrow so there is insufficient space to make other blood cells
What are the types of ALL?
- B-lymphoblastic leukaemia
- T-lymphoblastic leukaemia
What is the most common type of ALL?
B-lymphoblastic leukaemia
Where is the typing of ALL important?
In determining treatment
What is the typing of ALL based on?
What type of blood cell has become cancerous
What are the risk factors for ALL?
- Radiation exposure
- Genetic conditions
- Exposure to chemicals
- Infection
When can radiation exposure increase the risk of ALL?
When the person has been exposed to very high radiation levels, e.g. following a nuclear accident
Why is radiation exposure not much of a concern in the UK?
Because very few people in the UK will have been exposed to sufficient levels of radiation to increase their risk
Does living near a power plant increase the risk of ALL?
There is very little evidence for this
Give 2 examples of genetic conditions that increase the risk of ALL?
- Down’s syndrome
- Fanconis anaemia
What chemicals can increase the risk of ALL?
Industrial chemicals, e.g. benzene and other solvents
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
Are there any specific infections that have been found to cause leukaemia?
No
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
What are the most common sites of recurrent and severe infection in ALL?
- Oral
- Throat
- Skin
- Perianal
What causes LUQ fullness and splenomegaly in ALL?
Splenomegaly
What causes dyspnoea in ALL?
Anaemia, or large mediastinal mass
In which kind of ALL might dyspnoea due to a large mediastinal mass present?
T-cell leukaemia
What causes headache, irritability, or altered mental status in ALL?
CNS involvement
What causes haemorrhagic or thrombotic complications in ALL?
Thrombocytopenia or DIC
Give 3 examples of haemorrhagic or thrombotic complications of ALL
- Menorrhagia
- Frequent nosebleeds
- Spontaneous bruising
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
What causes petechiae in ALL?
Thrombocytopenia
What might petechiae progress to in ALL?
- Purpura
- Ecchymoses
What causes abdominal distention in ALL?
- Hepatomegaly
- Splenomegaly
What is leukaemia cutis?
google it (im on a train)
What are the differential diagnoses of ALL?
- Infection
- Myeloproliferative or lymphoproliferative disorders
- Myelodysplasia
- Aplastic anaemia
- Idiopathic thrombocytopenia
- Lymphoma
- Metastatic cancer
Give 2 examples of infections that may be differentials for ALL?
- EBV
- Parvovirus 19
What investigations should be done in ALL?
- Blood tests
- Bone marrow biopsy
- Immunophenotyping
- Lumbar puncture
- General health checks
What blood tests should be done in ALL?
- FBC
- Blood film
- Clotting
- LDH
- Liver and renal function
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
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
What may be found on clotting in ALL?
DIC
What indicates DIC on a clotting screen?
- Elevated prothrombin time
- Reduced fibrinogen level
- Presence of fibrin degradation produces
What happens to LDH in ALL?
Usually raised
Why do you need to do liver and renal function in ALL?
Should be checked before initiating chemotherapy
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
What is the standard procedure for obtaining a bone marrow sample in ALL?
Aspiration
When may core biopsy be done in ALL?
If aspiration does not yield sufficient cells
What is the purpose of immunophenotyping in ALL?
Helps reveal subtype
How can a positive confirmation of lymphoid rather than myeloid origin be achieved in ALL?
By flow cytometric demonstration of lymphoid antigens
Why is immunophenotyping important in ALL?
Therapeutically, it is important to differentiate between T-cell, mature B-cell, and B-cell precursor phenotypes
What can ALL be classified into (think ive already asked this lol)?
- B-cell ALL
- T-cell ALL
What can B-cell ALL be further classified into?
- Early pre-B cell ALL
- Common ALL
- Pre-B ALL
- Mature B-cell ALL
What can T-cell ALL be further classified into?
- Pre-T ALL
- Mature T-cell ALL
What does treatment for ALL typically consist of?
- Remission induction
- Consolidation (or intensification)
- Maintenance (or continuation) therapies
- CNS prophylaxis
- Management of relapse
What is the exception to the typical treatment for ALL?
Mature B-cell ALL
How is mature B-cell ALL managed?
Short-term intensive chemotherapy
What is involved in the general supportive treatment of ALL?
- Replacement therapy of blood cells
- Antibiotic and antifungal agents
Why is replacement therapy of blood cells important in ALL?
Pre-existing deficiency due to ALL can be profoundly aggravated by chemotherapy
What is the purpose of antibiotics and antifungal treatment in ALL?
Treat opportunistic infection
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
When should treatment be started for ALL?
Immediately
What might be given before induction therapy in ALL?
Pre-phase therapy
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
How long is pre-phase therapy given for in ALL?
5-7 days
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
How good are current treatment regimes for induction in ALL?
Achieve complete remission rates of 80-90%
When is maintenance therapy initiated in ALL?
Once normal haemopoiesis is achieved
What does maintenance therapy usually consist of in ALL?
Daily chemotherapy (6-metacaptopurine) and weekly methotrexate
How is 6-metacaptopurine administered?
Orally
What treatment duration is recommended for maintenance therapy in ALL?
2.5-3 years
Why is CNS prophylaxis given in ALL?
Because patients frequently have meningeal leukaemia at the time of relapse
What is the incidence of meningeal leukaemia in the absence of CNS prophylaxis?
50-75% in one year
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
What is included in intrathecal triple therapy for CNS prophylaxis in ALL?
- Methotrexate
- Steroids
- Cytarabine
What does stem cell transplantation allow for in ALL?
Intensification of chemotherapies and radiotherapies
How does stem cell transplantation allow for intensification of chemotherapies and radiotherapies?
It replaces destroyed stem cells
Describe the prognosis of relapse of ALL?
Very poor
What is the result of relapse of ALL having a very poor prognosis?
Most patients are referred for trial ‘salvage’ therapies
What are the factors predicting a good outcome after salvage therapies in ALL relapse?
- Young age
- Short duration of first remission
What is the outcome of ALL related to?
The age of the patient
What are the cure rates of childhood ALL?
80-90%
What are the cure rates of ALL in elderly/frail patients?
<10%
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
