Leukaemia Flashcards
Describe the steps from developing an acute leukaemia to bone marrow failure
malignant transformation of haematopoeitic stem cells ——–> cells proliferate but don’t differentiate ——-> accumulation of leukaemic blast cells in marrow —–> marrow failure
What cells are affected by AML?
Red Blood Cells
Monocytes
Granulocytes
Megakaryocytes
What cells are affected by ALL?
B Cells
T Cells
What do you look for in a cytochemical stain in acute leukaemias?
TdT+ in lymphoblasts - ALL
Myeloperoxidase in myeloblasts - AML
What supportive measures are given for all leukaemias?
Blood products - irradiated
Allopurinol
GCSF
Antibodies
How is philadelphia + ALL managed?
Stem cell transplant
Imatinib
TKI’s - tyrosine kinase inhibitors
What is APL? What genetics is it associated with?
Acute Promyelocytic Leukaemia
translocation of chromosome 15 and 17 t(15;17)
How does APL normally present? Describe the pathophysiology of this
Younger than AML and it’s other subtypes (age 25 ish)
build up of promyelocytes –> lots of Auer rods –> high coagulation risk –> DIC
Medical Emergency!
How is APL treated?
It responds to retinoic acid (ATRA)
What is myelodysplastic syndrome?
What would the bone marrow look like?
How would it present?
Condition which is a precursor of AML
Blasts build up in marrow but <20%
Same signs - cytopaenia, bruising etc.
How is myelodysplastic syndrome managed?
<5% blasts - conservative management with transfusions and antibiotics
> 5% blasts - treat like AML - chemo or bone marrow transplant
Describe the age presentation of ALL vs AML
ALL is childhood (2-5)
AML is adults (65)
How does ALL present?
Penia symptoms Bone pain Hepatosplenomegaly Fever Testicular enlargement mediastinal involvement = airway obstruction
What are the blood results in ALL?
normocytic, normochromic anaemia
thrombocytopenia
leukocytosis but with neutropenia
reduced reticulocytes
Renal failure: raised K and phosphate
raised LDH
What is the bone marrow like in ALL?
hypercellular
blast cell infiltration
On cytochemical staining, what is seen in ALL? Compare this to AML?
blasts are TDT+ve
In AML it is myeloperoxidase +ve
What are the poor prognostic factors for ALL?
male
non white
age <2 or >10
chromosomal translocations eg Philadelphia
high WCC
B or T cell surface makers (seen on immunophenotyping flow cytometry)
Describe how anaemia, thromboyctopenia, neutropenia and leukocytosis present
anaemia: tired, SOB, pale, weak
thrombocytopenia: bleeding and bruising
neutropenia: recurrent infections
leukocytosis: pro-thrombotic
How does AML present?
Similar to AML: Penia symptoms Bone pain Splenomegaly \+ gingival hyperplasia \+ purple skin nodules
What is seen on the blood film of AML?
Blast cells with Auer rods
Characteristics of the bone marrow in AML?
Hypercellular
>20% Blast cells
Poor prognostic features of AML?
> 60
20% blasts after first chemo
chromosome deletions
What is CLL?
a type of low grade B cell non-hodgkins lymphoma
How does CLL present?
often asymptomatic and picked up as incidental lymphocytosis \+ lymphadenopathy \+ B symptoms \+ penia symptoms \+ splenomegaly
What are the blood test results of CLL?
Lymphocytosis (Raised WCC)
anaemia
thrombocytopenia
What is seen on a blood film in CLL?
Smudge/smear cells
Lymphocytosis
NOT blasts
What are the complications of CLL?
Hyperviscosity = thrombotic events
Warm autoimmune haemolytic anaemia
Hypogammaglobulinaemia = infections
Richter Transformation
What is hypogammaglobulinaemia and what does it lead to?
It results in a lack of antibodies and therefore infections
What is Richter transformation? What is the pathophysiology? How does it present?
Transformation of CLL to a high grade lymphoma
Due to leukaemia cells infiltrating the lymph node
SUDDEN deterioration of symptoms
- B symptoms
- lymph node swelling
- abdo pain and nausea
How does CML present?
Massive splenomegaly = abdo discomfort
B symptoms
Penia symptoms
Blood results seen in CML?
+++ leukocytosis
normocytic, normochromic anaemia
Thrombocytosis progresses to penia
What is seen on a blood film of CML? and what is seen in the bone marrow?
Granulocytes at all different stages of development
BM: hypercellular with ++ granulocytes
What cytogenetic findings suggest CML?
Philadelphia!! Seen in 95% of patients with CML
What is the Philadelphia chromosome?
Translocation of the long arm of 9 and 22. This leads to a BCR-ABL gene. This codes for +++tyrosine kinase activity
How is CML managed?
Imatinib: tyrosine kinase inhibitor
Leukophoresis
What are the complications of CML?
Thrombotic event
Blast transformation to an acute leukaemia
