Leukaemia: AML, ALL, CML, CLL Flashcards
Define leukaemia?
Group of malignant cancers characterised by overproduction of immature and abnormal mature leukocytes, which suppress formation of other blood cells
Leukaemia is a cancer of what blood cell lineage?
Leukocytes (WBCs)
How does leukaemia characteristically affect formation of other blood cell lineages?
Suppresses formation of other blood cell types
Why is leukaemia classed as either myeloid or lymphoid?
Classed as myeloid (originates from myeloid cell lineage)
or
lymphoid (originates from lymphoid cell lineage)
How many main types of leukaemia are there, and what are they called?
4 main types:
Acute Myeloid Leukaemia (AML)
Chronic Myeloid Leukaemia (CML)
Acute Lymphoblastic/Lymphocytic Leukaemia (ALL)
Chronic Lymphoblastic/Lymphocytic Leukaemia (CLL)
Why is leukaemia classed as either acute or chronic?
Classed as acute (predominantly originates from immature cells)
or
chronic (predominantly originates from mature cells)
Define CLL, in terms of classification?
Chronic Lymphoblastic/Lymphocytic Leukaemia (CLL): Characterised by clonal proliferation of mature B-lymphocytes
What is the most common type of leukaemia?
CLL
At what age does CLL typically present?
Over 70 yrs old
Describe the speed of progression of CLL?
Usually progresses slowly
Does a patient with CLL typically present as symptomatic or asymptomatic, and why?
Asymptomatic
Because it generally progresses slowly
In the clinical presentation of symptomatic CLL, what are the 4 characteristic findings?
Lymphadenopathy
Splenomegaly
Symptoms of anaemia eg. pallor, TATT
Symptoms of thrombocytopenia eg. easily bruises or bleeds
How is CLL usually initially diagnosed during investigation?
Incidental lymphocytosis finding on FBC
If a patient has lymphadenopathy but no lymphocytosis on the FBC, can this still be diagnosed as CLL?
No, CLL must have lymphocytosis finding
Diagnosed as a Small Lymphocytic Lymphoma (SLL), which is a low-grade Non-Hodgkin lymphoma
What are the 2 hallmark findings for CLL on a blood film?
Lymphocytosis (lymphocytes with large nucleus and very thin cytoplasm border)
Smudge/smear cells (ruptured lymphocytes with irregular cytoplasm border)
What is immunophenotyping?
Lab test that uses a monoclonal antibody with an attached fluorescent maker to identify different antigens
What lab investigation is used to confirm CLL diagnosis?
Immunophenotyping
What is the hallmark finding of CLL, on immunophenotyping?
Co-expression of CD5 (T-cell antigen) and CD19 (B-cell antigen)
When do you start treatment for a patient with CLL?
Only treat patient when they become symptomatic, otherwise watch and wait
What are the most common medications used to treat CLL?
Combination of cytotoxic chemotherapy and monoclonal antibodies
eg. Rituximab + fludarabine + cyclophosphamide
What new drug class can be used to treat CLL, and give 2 examples?
B-cell signaling inhibitor tablets
e.g. ibrutinib, venetoclax
Define CML, in terms of classification?
Chronic Myeloid Leukaemia (CML): Characterised by clonal proliferation of mature granulocytes
What is the pathophysiology of CML?
Philadelphia chromosome translocation between chromosomes 9 and 22 causes BCR-ABL protein (tyrosine kinase) to switch on myeloid cell production
Does a patient with CML typically present as symptomatic or asymptomatic, and why?
Usually asymptomatic, as the chronic phase progresses slowly
Compare the clinical presentation of symptomatic CML to CLL?
Similar presentation of splenomegaly, lymphadenopathy, anaemia, thrombocytopenia, neutropenia symptoms and signs
CML presents also with night sweats and weight loss
How is CLL usually initially diagnosed during investigation?
Incidental lymphocytosis finding on FBC
Other than neutrophilia, what are 4 findings on a FBC of a patient with CML?
Thrombocytosis or thrombocytopenia
Eosinophilia
Basophilia
Anaemia
What is the blood film hallmark for CML?
Neutrophilia
Which 2 lab investigations are used to confirm a CML diagnosis?
FISH
Bone marrow aspirate
What will the FISH investigation show to confirm CML?
Philadelphia translocation
What will the bone marrow aspirate show to confirm CML?
Excess myeloid cells
What is the FISH investigation, and why is it useful for diagnosing CML?
FISH (Fluorescent In-Situ Hybridisation) identifies specific chromosome translocations by providing fusion signal (yellow coloured)
Will identify Philadelphia translocation
How does the bone marrow aspirate from a patient with CML correlate to their progression?
Shows state of progression between chronic and acute phase
When do you start treatment for a patient with CML?
Immediately after diagnosis
Otherwise could progress to AML
What is the first-line drug class for CML treatment, and how long must the patient take these for?
Tyrosine Kinase Inhibitors (TKI) eg.imatinib
Taken daily for rest of life
How can TKIs treat CML, and how is this monitored?
Patient aims to have very low BCR-ABL protein as TKI blocks it
Monitored using PCR of blood
Define ALL, in terms of classification?
Acute Lymphoblastic/Lymphocytic Leukaemia (ALL): Characterised by clonal proliferation of lymphoblasts (lymphocyte precursors)
Define AML, in terms of classification?
Acute Myeloid Leukaemia (AML):Characterised by clonal proliferation of myeloblasts (myeloid cell precursors)
Compare the epidemiologies of ALL and AML?
ALL: More common in children
AML: More common in adults and elderly
Compare the clinical presentation of ALL and AML?
Both present with symptoms of pancytopenia: Lethargy, fever and infections, easily bleed and bruise, symptoms of anaemia
ALL patients can sometimes present with hepato-splenomegaly
Compare the speed of onset of ALL and AML?
Speed of onset is usually fast, as history is short
Why is hepato-splenomegaly less common in acute leukaemia than chronic leukaemia?
Hepato-splenomegaly is an adaptation so can take time to occur
What must a blood film show to confirm an acute leukaemia diagnosis?
Over 20% blast cells
Why is blood film not reliable to distinguish between ALL and AML?
Lymphoid and myeloid blasts both have high nuclear:cytoplasmic ratio and distinct nucleoli
What lab investigation is used to distinguish between ALL and AML?
Immunophenotyping
What blood film finding can indicate AML instead of ALL?
Auer rods
What is meant by cancer remission, and is this absolute?
Cancer is not detected
Patients still have risk of cancer returning: Relapse
What is the correlation between curative chemotherapy for acute leukaemias and patient age?
The more elderly a patient is, the less likely they are to tolerate curative chemotherapy
Give one benefit and one disadvantage of intensive chemotherapy?
Chance of cure but is very toxic and has life-threatening complications associated
Give one benefit and one disadvantage of low-intensity chemotherapy?
Prolongs life but not curative, still is toxic
When palliative care is the chosen treatment for acute leukaemia, what is the main focus?
Symptom control with minimal time in hospital
