Haematological Malignancy Flashcards
What is 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.
What is pancocytopenia?
combination of low red blood cells (anaemia), white blood cells (leukopenia) and platelets (thrombocytopenia)
In what ages do different leukaemias occur?
“ALL CeLLmates have CoMmon AMbitions”
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 si the most common malignancy affecting children
Acute lymphoblastic leukaemia (ALL)
Acute lymphoblastic leukaemia (ALL) accounts for 80% of childhood leukaemias
true
What is the aetiology of ALL?
eak incidence is at around 2-5 years of age and boys are affected slightly more commonly than girls
What symptoms do you get in bone marrow failure?
anaemia: lethargy and pallor
neutropaenia: frequent or severe infections
thrombocytopenia: easy bruising, petechiae
What symptoms do you get in ALL?
Pancocytopenia sx
bone pain (secondary to bone marrow infiltration)
splenomegaly, hepatomegaly
fever is present in up to 50% of new cases (representing infection or constitutional symptom)
testicular swelling
What types of ALL do you get?
common ALL (75%), CD10 present, pre-B phenotype
T-cell ALL (20%)
B-cell ALL (5%)
What are some poor prognostic factors of ALL?
age < 2 years or > 10 years WBC > 20 * 109/l at diagnosis T or B cell surface markers non-Caucasian male sex
Chronic lymphocytic leukaemia (CLL) is caused by?
monoclonal proliferation of well-differentiated lymphocytes which are almost always B-cells (99%)
What is the most common form of leukaemia seen in adults?
CLL
How does CLL often present?
often no symptoms: may be picked up by an incidental finding of lymphocytosis
constitutional: anorexia, weight loss
Also, bleeding, infections
lymphadenopathy is more marked in CLL or CML?
lymphadenopathy more marked in CLL than chronic myeloid leukaemia
What is the key investigation for CLL?
immunophenotyping
What will you see on FBC in CLL?
lymphocytosis
anaemia
What will you see on blood film in CLL?
smudge cells (also known as smear cells)
What are the complications of CLL?
anaemia
hypogammaglobulinaemia leading to recurrent infections
warm autoimmune haemolytic anaemia in 10-15% of patients
Richter’s transformation
What is Richter’s Transfromation?
Complication of CLL
Ritcher’s transformation occurs when leukaemia cells enter the lymph node and change into a high-grade, fast-growing non-Hodgkin’s lymphoma.
How does Richter’s transformation present?
Patients often become unwell very suddenly.
lymph node swelling
Constitutional: fever without infection, weight loss, night sweats
nausea, abdominal pain
Which chromosome is associated with chronic myeloid leukaemia?
The Philadelphia chromosome is present in more than 95% of patients with chronic myeloid leukaemia (CML)
What is the Philadelphia Chromosome? What gene does it result in?
It is due to a translocation between the long arm of chromosome 9 and 22 - t(9:22)(q34; q11).
This results in part of the ABL proto-oncogene from chromosome 9 being fused with the BCR gene from chromosome 22.
The resulting BCR-ABL gene codes for a fusion protein which has tyrosine kinase activity in excess of normal
What age group does CML present in?
60-70
How does CML present?
anaemia: lethargy
weight loss and sweating are common
splenomegaly may be marked → abdo discomfort
What would investigations of CML show?
an increase in granulocytes at different stages of maturation +/- thrombocytosis
decreased leukocyte alkaline phosphatase
may undergo blast transformation (AML in 80%, ALL in 20%)
What does BCR ABL do?
tyrosine kinase activity in excess of normal
What is first line for CML? What other options are there?
imatinib is now considered first-line treatment
hydroxyurea
interferon-alpha
allogenic bone marrow transplant
How does Imatinib work?
inhibitor of the tyrosine kinase associated with the BCR-ABL defect
Imanitib has high response rate in which phase of CML?
Chronic
Acute myeloid leukaemia is the more common form of acute leukaemia in adults.
true
AML may occur as a primary disease or following a secondary transformation of a myeloproliferative disorder
true
Feature of AML are largely related to bone marrow failure
true
What symptoms do you get in AML?
anaemia: pallor, lethargy, weakness
neutropenia: whilst white cell counts may be very high, functioning neutrophil levels may be low leading to frequent infections etc
thrombocytopenia: bleeding
splenomegaly
bone pain
What are poor prognostic factors of AML?
> 60 years
20% blasts after first course of chemo
cytogenetics: deletions of chromosome 5 or 7
How is AML classified?
French-American-British (FAB)
OUtline French-American-British (FAB)
MO - undifferentiated M1 - without maturation M2 - with granulocytic maturation M3 - acute promyelocytic M4 - granulocytic and monocytic maturation M5 - monocytic M6 - erythroleukaemia M7 - megakaryoblastic
Acute promyelocytic leukaemia M3 is associated with what?
associated with t(15;17)
fusion of PML and RAR-alpha genes
Acute promyelocytic leukaemia presents younger than other types of AML
true
25 yrs old avg
Acute promyelocytic leukaemia M3 has a bad prognosis
false
good
Acute promyelocytic leukaemia M3 will present with?
DIC or thrombocytopenia often at presentation
Acute promyelocytic leukaemia M3 will show what on myeloperoxidase stain?
Auer Rods
Lymphomas are a group of cancers that affect the lymphocytes inside the lymphatic system.
true
There are two main categories of lymphoma - what are they?
Hodgkin’s lymphoma and non-Hodgkin’s lymphoma. Hodgkin’s lymphoma is a specific disease and non-Hodgkins lymphoma encompasses all the other lymphomas.
Hodgkin’s lymphoma is a malignant proliferation of lymphocytes characterised by the presence of
the Reed-Sternberg cell.
Hodgkin’s lymphoma has a bimodal age distributions being most common in?
the third and seventh decades
Presntation of HL?
lymphadenopathy (75%) - painless, non-tender, asymmetrical
systemic (25%): weight loss, pruritus, night sweats, fever (Pel-Ebstein)
Bloods in HL?
normocytic anaemia, eosinophilia
LDH raised
Alcohol causes pain in HL
TRUE
Symptoms that imply a poor prognosis in HL are called?
‘B’ symptoms
What are ‘B’ symptoms
weight loss > 10% in last 6 months
fever > 38ºC
night sweats
What are the 4 classes of histology in HL?
Nodular sclerosing
Mixed cellularity
Lymphocyte predominant
Lymphocyte depleted
What is the commonest type of HL?
Nodular sclerosing Most common (around 70%)
What is the best prognosis of HL?
Lymphocyte predominant
Describe the frequency, prognosis and cells associated with Nodular Sclerosing HL?
Most common (around 70%)
Good prognosis
Associated with lacunar cells
Nodular Sclerosing HL is most common in women
true
Describe the frequency, prognosis and cells associated with Mixed Cellularity HL?
Around 20% Good prognosis Associated with a large number of Reed-Sternberg cells