HAEMATOLOGY - LEUKAEMIA Flashcards
What are the 4 main types of leukaemia?
Acute myeloid leukaemia
Acute lymphoid leukaemia
Chronic myeloid leukaemia
Chronic lymphoid luekaemia
Which leukaemia diseases are most common in childhood and which in the elderly?
Childhood - ALL
Elderly - CLL
What risk factors are associated with leukaemia?
Radiation
Chemicals e.g. benzene
Previous chemo
Inherited bone marrow failure conditions
Down’s syndrome
What conditions can predispose you to leukaemia?
fanconi anaemia
Down’s syndrome
Myelodysplastic syndrome
Myeloproliferative disorders
li-fraumeni syndrome
ataxia-telangiectasia
What chemicals and drugs can predispose you to leukaemia?
Benzene can cause marrow damage
Chemotherapy drugs such as alkylating agents and topoisomerase 2 inhibitors - linked to AML
What viruses are associated with leukaemia?
Human T-lymphocyte virus
HIV
Whats the difference between leukaemias and lymphomas?
Leukaemias are mutated white cells in the blood
Lymphomas are malignancies of the lymphoid system
Whats the difference in age demographic between acute myeloid and acute lymphoid leukaemia?
Acute myeloid as a median age of presentation of 65
Acute lymphoid has a substantially lower age of presentation and is the most common maliganncy in childhood
What are the symptoms of leukaemia?
Breathlessness, fatigue, angina and claudication = Anaemia
Infections = neutropenia
Bleeding and bruising = thrombocytopenia
Breathlessness, headache, confusion, visual problems = leucostasis
Bone pain = marrow infiltration
Headache = CNS infiltration
Gout = hyperuricaemia
What are the signs of leukaemia?
Pallor, cardiac flow murmur = anaemia
Fever, mouth ulcers, septic focus = neutropenia
Petechia, bleeding gums, fundal haemorrhage = thrombocytopenia
Hypoxia, pulmonary infiltrates, reduces GCS, retinal dilation, papilloedema, fundal haemorrhage = leucostasis
Hepatospelnomegaly = liver and spleen infiltration
Lymphadenopathy = lymph node infilatration
Cranial nerve palsies = cns infiltration
Renal stones/trophi = hyperuricaemia
What are some signs specific to AML?
Gum hypertrophy = gum infiltration
Granulocytic sarcomas = skin infiltration
What are some signs specific to ALL?
Testicular enlargement = testes infiltration
Mediastinal mass = mediastinum infiltration
How do you confirm a diagnosis for acute leukaemia?
Blood count - Hb and Plt low, WBC raised
Blood film - blast cells
Bone marrow aspirate - increased cellulairyt, reduced erythropoeisis, reduced megakaryocytes
Chest X-ray - mediastinal widening is often present in T-lymphoblastic leukaemia
CSF examination - risk of CNS involvement is high in ALL
Coagulation profile - to exclude presence of disseminated intravascular coagulation which is particularly associated with acute promyelocytic leukaemia
When should you refer an adult with suspected leukaemia?
Consider a very urgent FBC (within 48 hrs) to assess leukaemia in adults with any of the following:
Pallor, persistent fatigue, unexplained fever, unexplained persistent/recurrent infection, generalised lymphadenopathy, unexplained bruising, unexplained bleeding, unexplained petechia, hepatosplenomegaly
How do we define acute leukaemia?
proliferation of immature white blood cells that comprise more than 20% of the cells of the bone marrow or peripheral blood stream
Outline the pathology of Acute leukaemia?
Myeloid blast cells LOs their ability to differentiate and divide uncontrollably in the bone marrow which crowds out of normal cells. This leads to a loss of cells in the bone marrow (pancytopenias). Eventually blasts build up so much they spill out into the blood stream. Some blast cells settle down in organs causing them to enlarge
What would you see on a blood smear for AML?
> 20% myeloblasts (large cells with nuclei containing fine chromatin and prominent nucleoli)
Low amount of cytoplasm
Presence of myeloperoxidase (done by cytoplasmic staining or you can look for auer rods)
What are auer rods?
Crystallised versions/aggregates of myeloperoxidase
What are the subtypes of AML?
M1 - AML with minimal maturation
M2 - AML with maturation
M3- APL (acute promyelocytic)
M4 - Myelomonocytic
M5 - Monocytic
M6 - Acute erythroid leukaemia
M7 - acute megakaryblastic leukaemia
What is acute promyelocytic leukaemia?
Leukaemia arising from promyelocytes (more mature than blast cells)
Caused by translocation of 15;17 which produced a fusion gene PML/RAR alpha which disrupts the retinoic acid receptor alpha gene which usually regulates cell division
Why is acute promyelocytic leukaemia a medical emergency?
These cells have a lot of auer rods which increase the coagulation risk, making it a medical emergency from disseminated intravascular coagulation
How do you treat acute promyelocytic leukaemia?
All transretinoic acid - a derivative of vitamin A which binds to disrupted retinoic acid receptor and causes the blasts to mature into neutrophils to lift some leukaemia burden
Followed by chemotherapy
Which leukaemia can cause swollen gums?
Acute Monoblastic leukaemia
Which type of AML has an association of Down’s syndrome before the age of 5?
Acute megakaryoblastic leukaemia -
Which leukaemia has Down syndrome as a risk factor?
Acute megakaryoblastic leukaemia before the age of 5
ALL
Which conditions can lead to AML?
Myelodysplastic syndrome
Myelodysplasia
What can a haematopoetic stem cell differentiate into?
Common myeloid progenitor and common lymphoid progenitor
What can a common myeloid pregenitor differentiate into?
Erythrocyte, thrombocyte or a myeloblast
What can a common lymphoid pregenitor cell differentiate into?
Lymphoblast
What can a lymphoblast differentiate into?
T cell
B cell
NK cell
What are the leukocytes?
Neutrophil, basophil, eosinophil, monocyte, B lymphocytes, T lymphocytes and NK cell
What are the 2 common chromosomal translocations that cause ALL?
T(12;21) and t(9;22) which result in the production of abnormal cell proteins which affects cells function and division
What are the 2 types of ALL?
B cell ALL (70-80% of cases)
T cell ALL
What is ‘AML with a background of myelodysplasia’?
When you have myelodysplastic syndrome causing a build up in blast cells and eventually the disease progresses and blast percentage may go over 20%
Why is Down syndrome associated with AML and ALL?
Due to an extra copy of chromosome 21 and common causes of leukaemia are due to translocations involving this chromosome
Which 2 symptoms are more likely in ALL than AML but can be seen in both?
Feeling of abdominal fullness - hepatosplenomegaly
Lymphadenopathy
This is because lymphoblasts are more likely to deposit in the spleen, liver and lymph nodes