Haem- malignancy Flashcards
what is leukaemia
a group of blood cancers with an increase in white blood cells
what is chronic myeloid leukaemia
Proliferation of myeloid cells - granulocytes and their precursors, other lineages (platelets)
what genetic abnormality is characteristic of chronic myeloid leukaemia (CML)
Philadelphia chromosome- t(9:22)
Philadelphia chromosome results in a new gene-
BCR-ABL1
what are the three phases of CML
chronic phase
accelerated phase
blast phase
how long can the CML chronic phase last and how is it often discovered
can last around 5 years
often asymptomatic discovered incidentally through raised WBC count
CML accelerated phase
high proportion of the cells in the bone marrow and blood (10-20%)
patients become more symptomatic, develop anaemia, thrombocytopenia, and become more immunocompromised
CML blast phase
high proportion of blast cells (>30%)
This phase has severe symptoms and pancytopenia
It is often fatal
CF of CML
asymptomatic
splenomegaly
hyper metabolic symptoms
gout
treatment of CML
tyrosine kinase inhibitors e.g. imatinib
MOA of tyrosine kinase inhibitors e.g. imatinib
Prevents the action of theBCR-ABL fusion protein i.e.this is the abnormal protein produced by the Ph mutation
what is acute myeloid leukaemia
malignant disease of primitive myeloid cells (excess of myeloblasts)
acute myeloid leukaemia common age range
> 60 years
what is acute lymphoblastic leukaemia
Malignant disease of primitive lymphoid cells (lymphoblasts)
what is the most common childhood cancer
acute lymphoblastic leukaemia
what syndrome is ALL often associated with?
Down syndrome
CF of ALL
marrow failure- anaemia, infections, bleeding
leukaemic effects
bone pain
abnormal cells ‘blasts’ features
large size
high nuclear:cytoplasmic ratio
prominent nucleolus
blood film specific to AML
Auer rod- Blast cells have rods inside their cytoplasm
diagnostic tool required for definite diagnosis of AML/ALL
immunophenotyping
multi-agent chemotherapy in AML
intensive chemo (3-4 cycles)
prolonged hospitalisation
multi-agent chemotherapy in ALL
can last up to 2-3 years
different phases of treatment at varying intensity
what is a Hickman line
used to provide long-term central venous access
complications of acute leukaemia
anaemia
neutropenia
thrombocytopenia
neutropenia complication
infections- increased severity and duration
gram negative bacteria can cause life threatening sepsis in neutropenic patients
prolonged neutropenia makes patients susceptible to fungal infections
thrombocytopenia complication
bleeding- purport, petechiae
complications of anti-leukaemic treatment
nausea and vomitting
hair loss
liver, renal dysfunction
tumour lysis syndrome
infection
late affects (eg infertility, cardiomyopathy)
single most important prognostic factor in AML
cytogenic type
females/males have better prognosis in ALL?
females
what is chronic lymphocytic leukaemia
chronic proliferation of a single type of well differentiated lymphocyte, usuallymature B-lymphocytes
common age range for CLL
> 55 years
CF of CLL
asymptomatic
non-specific (night sweats etc)
lymph node/spleen enlargement
infections
bleeding
warm autoimmune haemolytic anaemia
blood film findings in CLL
> lymphocytes
smear cells
what does the BCR-ABL1 gene code for
tyrosine kinase
first and second line treatment for chronic myeloid leukaemia
first line- imatinib
second line- dasatinib
at what age does acute lymphoblastic leukaemia typically peak
2-4 years
Is Acute Lymphoblastic Leukaemia (ALL) associated with any chromosomal abnormalities?
Yes, the Philadelphia chromosome (t(9:22) translocation) is associated with ALL in 30% of adults and 3-5% of children
what type of lymphocytes are usually involved in ALL
B-lymphocytes
by definition, how many ‘blasts’ are required in the peripheral blood or bone marrow for a diagnosis of acute leukaemia
at least 20% blasts in either peripheral blood or bone marrow
what cytogenetic abnormalities are commonly found in chronic lymphocytic leukaemia (CLL)
deletion of 13q (most common)
trisomy 12
what are the absolute indications for treatment in chronic lymphocytic leukaemia
weight loss of over 10% over 6 months
night sweats for more than 1 month
progressive marrow failure (anaemia or thrombocytopenia)
what is a major complication of chronic lymphocytic leukaemia
can transform into a high-grade lymphoma
what is Richter’s transformation
development from chronic lymphocytic leukaemia into aggressive lymphoma, usually diffuse large B-cell lymphoma
which type of leukaemia is often associated with myelodysplastic syndromes but can arise ‘de novo’
acute myeloid leukaemia
what is lymphoma
group of cancers that affect the lymphocytes inside the lymphatic system; cancerous cells proliferate within lymph nodes and cause lymph nodes to become abnormally large
what percentage of lymphomas does Hodgkins lymphoma account for
1/5 of all lymphomas
cause of Hodgkins lymphoma
proliferation of lymphocytes
what are the two age peaks of Hodgkins lymphoma
age 20
age 75
risk factors of Hodgkins lymphoma
immunosuppression (eg HIV)
autoimmune disorders (eg rheumatoid arthritis, sarcoidosis)
epstein-barr virus (EBV)
family history
what is Burkitt lymphoma associated with
epstein-barr virus
malaria
HIV
what is MALT lymphoma and what is it associated with
affects the mucosa-associated lymphoid tissue, usually around the stomach
associated with H.pylori infection
How does Diffuse large B cell lymphoma typically present in patients over 65 years?
rapidly growing painless mass
risk factors for non-hodgkins lymphoma
infections- HIV, EBV, H.pylori
hepatitis b or c infection
Exposure to pesticides and a specific chemical calledtrichloroethyleneused in several industrial processes
family history
clinical features of lymphoma
enlarged lymph nodes- non tender, rubbery, may be painful when drinking alcohol
systemic symptoms
itch without rash
what is the significance of LDH in blood tests for Hodgkins lymphoma
LDH often raised in Hodgkins lymphoma, but it is not specific and can be elevated in other cancers and many non-cancerous diseases
what blood results are associated with a poor prognosis in Hodgkins lymphoma
elevated ESR and/or decreased haemoglobin
what is the key diagnostic test for Hodgkins lymphoma
lymph node biopsy
what is the key finding in a lymph node biopsy for hodgkins lymphoma
the reed-sternberg cell- abnormally large b cells with multiple nuclei and nucleoli inside them
what is the Ann-arbor system
used for staging Hodgkins lymphoma, compromising four key stages (I-IV) with possible subcategories (A and B)
What does Stage I in the Ann-Arbor staging system represent?
presence of single lymph node involved
What does Stage II in the Ann-Arbor staging system represent?
Stage II involves two or more lymph nodes/regions on the same side of the diaphragm
What does Stage III in the Ann-Arbor staging system represent?
Stage III involves nodes on both sides of the diaphragm
What does Stage IV in the Ann-Arbor staging system represent?
spread beyond the lymph nodes to other organs or tissues
what is the primary treatment of Hodgkins lymphoma
multi-agent chemotherapy with/without radiation
what does the acronym ABVD stand for in Hodgkin lymphoma treatment
adriamycin
bleomycin
vinblastine
dacarbazine
what potential side effect is associated with bleomycin in Hodgkin lymphoma treatment
pneumonitis
good/bad cure rates in Hodgkins lymphoma?
good, especially in younger patients
What does the acronym R-CHOP stand for in Non-Hodgkin lymphoma treatment?
Rituximab
cyclophosphamide
hydroxydaunorubicin
vincristine (oncovin)
prednisolone
what are some risks associated with R-CHOP treatment of non-hodgkins lymphoma
neutropenia
cardiotoxicity
which type of lymphoma causes a classical ‘starry sky appearance’ on lymph node aspirate histology
burkkitts lymphoma
which chromosomal translocation is associated with burkitts lymphoma
translocation between chromosomes 8 and 14
what is the median age of diagnosis for polycythaemia vera (PV)
~65, but can affect younger patients
what genetic mutation is present in over 95% of PV patients
JAK2 kinase mutation (substitution)
what is polycythaemia vera (PV)
rare blood cancer where bone marrow produces too many red blood cells
which type of haematological malignancy is associated with aquagenic pruritus
polycythaemia vera (PV)
target haematocrit in PV management
<0.45
what procedure is used to reduce haematocrit in PV patients
venesection
what is an example of a cytotoxic oral chemotherapy used in PV
hydroxycarbamide
JAK2 mutations in approx how many patients with essential thrombocytaemia
50-60%
what is idiopathic myelofibrosis
healthy bone marrow replaced by fibrosis, resulting in a lack of production of normal cells
what mutations are associated with idiopathic myelofibrosis
JAK2
CALR
MPL gene
teardrop shaped RBCs in peripheral blood characteristic of-
idiopathic myelofibrosis
