Haem - Leukaemia Flashcards
Leukaemia - what is the difference between acute leukaemia and chronic leukaemia?
Acute leukaemia is a result of impaired cell differentiation, resulting in large numbers of malignant precursor (blast) cells in the bone marrow
Chronic leukaemia is the result of excessive proliferation of mature malignant cells, but cell differentiation is unaffected
Leukaemia - what is the difference between myeloid and lymphocytic leukaemia?
The difference between myeloid leukaemia and lymphocytic leukaemia is that myeloid leukaemia commonly arises from a myeloid precursor cell, such as neutrophils
Lymphocytic leukaemia arises from a lymphoid precursor, such as B-cells
What do myeloblasts and lympoblasts differentiate into?
What is the general pathophysiology of leukaemia?
- Leukaemia is a form of cancer of the cells in the bone marrow
- A genetic mutation in one of the precursor cells in the bone marrow leads to excessive production of a single type of abnormal white blood cell
- The excessive production of a single type of cell can lead to suppression of the other cell lines causing underproduction of other cell types
- This results in a pancytopenia, which is a combination of low red blood cells (anaemia), white blood cells (leukopenia) and platelets (thrombocytopenia)
What is the mnemonic to remember the progressive ages of the different leukaemias?
“ALL CeLLmates have CoMmon AMbitions” to remember the progressive ages of the different leukaemia from 45-75 in steps of 10 years
Remember that ALL (the first in the mnemonic) most commonly affects children under 5 years.
- Under 5 and over 45 – acute lymphoblastic leukaemia (ALL)
- Over 55 – chronic lymphocytic leukaemia (CeLLmates)
- Over 65 – chronic myeloid leukaemia (CoMmon)
- Over 75 – acute myeloid leukaemia (AMbitions)
What are differential facts to help differentiate between the 4 leukaemia’s?
Acute lymphoblastic leukaemia: Most common leukaemia in children. Associated with Down syndrome
Chronic lymphocytic leukaemia: Most common leukaemia in adults overall. Associated with warm haemolytic anaemia, Richter’s transformation into lymphoma and smudge / smear cells
Chronic myeloid leukaemia: Has three phases including a 5 year “asymptomatic chronic phase”. Associated with the Philadelphia chromosome
Acute myeloid leukaemia: Most common acute adult leukaemia. It can be the result of a transformation from a myeloproliferative disorder. Associated with Auer rods
Differential diagnosis of Petechiae?
One of the key presenting features of leukaemia is bleeding under the skin leading to bruising and petechiae. This is caused by thrombocytopenia (low platelets)
- Leukaemia
- Meningococcal septicaemia
- Vasculitis
- Henoch-Schonlein Purpura (HSP)
- Idiopathic Thrombocytopenia Purpura (ITP)
- Non-accidental injury
Acute myeloid leukaemia (AML) - what is it?
Most common acute leukaemia in adults
May occur as primary disease or secondary transformation of a myeloproliferative disorder
AML - what are the clinical features?
Bone marrow failure symptoms:
Fatigue - due to anaemia
Easier bleeding - due to thrombocytopenia
More infections - due to leukopenia
Pain and tenderness in bones
AML - what are the signs of infiltration?
Hepatomegaly
Splenomegaly
Gum hypertrophy
AML - investigations, and diagnostic finding?
Blood film:
Will show high proportions of blast cells and Auer rods
AML - management?
Chemotherapy regimens
Bone marrow transplant
AML - prognosis?
Death occurs within 2 months without treatment; however, it is still poor in those who undergo treatment, with a 20% 3-year survival rate
Acute Lymphoblastic Leukaemia (ALL) - what is it?
ALL is the most common cancer of childhood
Caused by the abnormal clinical proliferation of lymphoid progenitor cells
These lymphoid precursors infiltrate normal haematopoietic cells of the bone marrow and other organs of the body
ALL - what is the peak age incidence?
2-5 years old in children
Adults over age of 45
ALL - what cell most commonly proliferates?
B-lymphocytes
ALL - what genetic condition is is commonly associated with?
Downs syndrome
ALL - what chromosome and translocation is it associated with?
It is associated with the Philadelphia chromosome (t(9:22) translocation) in 30% of adults and 3-5% of children with ALL
ALL - what are some clinical features?
Bone marrow failure symptoms of anaemia including fatigue, abnormal bleeding/bruising caused by low platelets, and infections caused by low white cells
Bone pain caused by infiltration
ALL - what are some signs?
Painless lymphadenopathy
Hepatosplenomegaly
CNS involvement (e.g. cranial nerve palsies, meningism)
Testicular infiltration (resulting in painless unilateral testicular enlargement)
ALL - how do you diagnose?
Bone marrow analysis and blood film - blast cells
Blood results - leukocytosis
ALL - management?
Chemotherapy regimens
ALL - prognosis in children?
Cure rate of 70-90%
Chronic myeloid leukaemia (CML) - what is it?
It is a leukaemia with three phases:
- Chronic phase - lasts around 5 years, often asymptomatic, patients diagnosed incidentally with raised WCC
- Accelerated phase - abnormal blast cells take up high proportion of the cells in BM and blood (10-20%), more symptomatic, develop anaemia and thrombocytopenia
- Blast phase - even higher proportion of blast cells and blood (>30%)
CML - what is the chromosomal defect present in more than 95% of patients?
Philadelphia chromosome, translocation between the long arm of chromosome 9 and 22
CML - common age of presentation?
60-70 years
CML - what are the clinnical features?
- weight loss and sweating are common
- anaemia: lethargy
- massive splenomegaly → abdo discomfort
- bleeding - due to thrombocytopenia
- gout
*
- gout
CML - diagnosis?
Leukocytosis - raised myeloid cell which include, neutrophils, monocytes, basophils, eosinophils
Granulocytes at different stages of maturation +/- thrombocytosis
CML - management?
1st line - Imatinib, very high response rate in chronic phase
Hydroxyurea
Interferon-alpha
allogenic BM transplant
Chronic lymphocytic leukaemia (CLL) - what is it?
Chronic lymphocytic leukaemia (CLL) is caused by a chronic monoclonal proliferation of well-differentiated lymphocytes which are almost always B-cells (99%)
It is the most common form of leukaemia seen in adults
CLL - how does it typically present?
Typically presents asymptomatically
CLL - what are the clinical features?
Non-tender lymphadenopathy (may be more marked than CML)
Hepatosplenomegaly
B symptoms - weight loss, night sweats, and fever
BM failure features - bleeding, infections, anaemia (less common than in acute Leukaemias)
CLL - investigations?
FBC - lymphocytosis, anaemia
Blood film - smudge cells (also known as smear cells)
Immunophenotyping - key Ix
CLL - characteristic finding on blood film?
Smudge or Smear cells
CLL - what are three complications?
- hypogammaglobulinaemia leading to recurrent infections
- warm autoimmune haemolytic anaemia in 10-15% of patients
- transformation to high-grade lymphoma (Richter’s transformation)
CLL - what is Richter’s transformation?
CLL can transform into high-grade lymphoma
CLL - when does Richter’s transformation occur?
Occurs when leukaemia cells enter the lymph node and change into a high-grade, fast-growing non-Hodgkin’s lymphoma
CLL - how does Richter’s transformation present?
Presents suddenly
CLL - what is Richter’s transformation indicated by?
- lymph node swelling
- fever without infection
- weight loss
- night sweats
- nausea
- abdominal pain
