Week 20 - Leukaemia, Lymphoma, Myeloma Flashcards
what is leukaemia
a cancer of a particular line of stem cells in the bone marrow, causing unregulated production of a specific type of blood cell
what are the four main types of leukaemia
- acute myeloid leukaemia
- acute lymphoblastic leukaemia
- chronic myeloid leukaemia
- chronic lymphocytic leukaemia
how are the types of leukaemia classed
depending on how rapidly they progress and the cell line that is affected
what is a more rare, less likely to appear in exams form of leukaemia
acute promyelocytic leukaemia
what leukaemia most commonly affects children under 5 years old
acute lymphoblastic leukaemia
which leukaemia is associated with Down’s syndrome and children
ALL
what leukaemia is associated with warm haemolytic anaemia, Richter’s transformation and smudge cells
CLL
how many phases does CML have and what is it associated with
has three phases, including a long chronic phase, and is associated with the Philidelphia chromosome
what may AML result in
a transformation from a myeloproliferative disorder and is associated with Auer rods
what does a genetic mutation in one of the precursor cells in the bone marrow lead to
excessive production of a single type of abnormal white blood cell
what can the excessive production of a single type of cells do to other cell lines
can suppress the other cell lines, causing the underproduction of different cell types.
this results in pancytopenia, which is a combination of low red blood cells , white blood cells and platelets
what are the potential presenting features for leukaemia
Fatigue
Fever
Pallor due to anaemia
Petechiae or bruising due to thrombocytopenia
Abnormal bleeding
Lymphadenopathy
Hepatosplenomegaly
Failure to thrive (children)
what is one key presenting feature of leukaemia
bleeding under the skin due to thrombocytopenia
what does bleeding under the skin cause
. Bleeding under the skin causes non-blanching lesions.
what are lesions of bleeding under the skin called; there are three names according to the different sizes
Petechiae are less than 3 and caused by burst capillaries
Purpura are 3 – 10mm
Ecchymosis is larger than 1cm
what are the top differentials for a non-blanching rash caused by bleeding under the skin
Leukaemia
Meningococcal septicaemia
Vasculitis
Henoch-Schönlein purpura (HSP)
Immune thrombocytopenic purpura (ITP)
Thrombotic thrombocytopenic purpura (TTP)
Traumatic or mechanical (e.g., severe vomiting)
Non-accidental injury
what do NICE recommend within 48 hours for patients with suspected leukaemia
a full blood count within 48 hours
what is used to look for abnormal cells and inclusions
a blood film
what is a very non-specific marker of tissue damage that is often raised in leukaemia
Lactate dehydrogenase (LDH)
it can be raised in literal heavy exercise too so it is not helpful for screeing
what is used to analyse the cells in the bone marrow to establish a definitive diagnosis of leukaemia
bone marrow biopsy
what are used to help stage the condition of leukaemia
CT and PET scans
where is a bone marrow biopsy usually taken from and what does it involve
the iliac crest
it involves a local anaesthetic and a specialist needle.
the options are aspiration or trephine. bone marrow aspiration involves taking a liquid sample of cells from within the bone marrow
what does bone marrow trephine involve
taking a solid core sample of the bone marrow and provides a better assessment of the cells and structure
what does ALL (acute lymphoblastic leukaemia) affect
ALL affects one of the lymphocyte precursor cells causing acute proliferation of a single type of lymphocyte, usually B lymphocyte
what does excessive accumulation of these cells lead to
replaces other cell types in the bone marrow leading to pancytopenia
what is chronic lymphocytic leukaemia
where there is a slow proliferation of a single type of well-differentiated lymphocyte, yet again usually the B lymphocyte
who does CLL usually affect
adults over 60 years of age
what does Richter’s transformation refer to
the rare transformation of CLL into high-grade B cell lymphoma
what are smear or smudge cells and what are they particularly associated with
Smear or smudge cells are ruptured white blood cells that occur while preparing the blood film when the cells are aged or fragile. They are particularly associated with chronic lymphocytic leukaemia.
what are the three phases of chronic myeloid leukaemia
chronic phase
accelerated phase
blast phase
what is the chronic phase of CML
often asymptomatic and patients are diagnosed after an incidental finding of a raised white cell count
this phase can last for several years before progressing
what is the accelerated phase of CML
occurs when the abnormal blast cells take up a high proportion of the bone marrow and blood cells
in the accelerated phase, patients are more symptomatic and devlop anaemia, thrombocytopenia and immunodeficiency
what phase does the blast phase come after
comes after the accelerated phase
what does the blast phase involve
an even higher proportion of blast cells in the blood
the blast phase has severe symptoms and pancytopenia,
it is often fatal
CML is associated with which chromosome
with the Philadelphia chromosome
this refers to an abnormal chromosome 22 caused by a reciprocal translocation of genetic material between a section of chromosome 9 and chromosome 22
what does this translocation in CML create
an abnormal gene sequence called BCR-ABL1 which codes for an abnormal tyrosine kinase enzyme that drives the proliferation of the abnormal cells
what is acute myeloid lukaemia presenation
normally presents form middle age onwards
what is AML a result of
transformation from a myeloproliferative disorder such as polycythaemia ruby vera or myelofiborisis
what will a blood film and bone marrow biopsy show in AML
show a high proportion of blast cells
auer rods in the cytoplasm of blast cells are a characteristc finding in AML
what is leukaemia mainly treated with
chemotherapy and targeted therapies, depending on the type and individual features
what are two examples of targeted therapies used in CLL
Tyrosine kinase inhibitors (e.g., ibrutinib)
Monoclonal antibodies (e.g., rituximab, which targets B-cells)
what are the other treatment options for leukaemia
radiotherapy
bone marrow transplant
surgery
what is tumour lysis syndrome and what does it result from
results from chemicals released when cells are destroyed by chemotherapy, resulting in;
- high uric acid
- hyperkalaemia
-high phosphate
- low calcium
what happens when there is high uric acid in the kidneys
uric acid can form crystals in the interstitial space and tubules of the kidneys, causing acute kidney injury.
what is required in patients before chemotherapy to prevent tumour lysis syndrome
Very good hydration and urine output before chemotherapy is required in patients at risk of tumour lysis syndrome. Allopurinol or rasburicase may be used to suppress the uric acid levels.
what type of cancer is lymphoma
type of cancer that affects the lymphocytes inside the lymphatic system
where do cancerous cells proliferate in lymphoma
inside the lymph nodes causing the lymph nodes to be abnormally large
what are the main two categories of lymphoma
Hodgkin’s lymphoma (a specific disease)
Non-Hodgkin’s lymphoma (which includes all other types)
what is the most common specific type of lymphoma
Hodgkin’s lymphoma
what kind of age distribution does Hodgkin’s have and what are the peaks
It has a bimodal age distribution with peaks around 20-25 and 80 years.
what are the risk factors for Hodkin’s lymphoma
HIV
Epstein-Barr virus
Autoimmune conditions, such as rheumatoid arthritis and sarcoidosis
Family history
what are the three notable types of non-Hodkin’s lymphoma
Diffuse large B cell lymphoma typically presents as a rapidly growing painless mass in older patients
Burkitt lymphoma is particularly associated with Epstein-Barr virus and HIV
MALT lymphoma affects the mucosa-associated lymphoid tissue, usually around the stomach
what are the risk factors for non-Hodkin’s lymphoma
HIV
Epstein-Barr virus
Helicobacter pylori (H. pylori) infection is associated with MALT lymphoma
Hepatitis B or C infection
Exposure to pesticides
Exposure to trichloroethylene (a chemical with a variety of industrial uses)
Family history
what is the key presenting symptom in lymphoma
lymphadenopathy
the enlarged lymph node or nodes might be in the neck, axilla, or inguinal region
what are the characterisitics of the enlarged lymph nodes
non-tender and feel firm or rubbery
patient’s with Hodgkin’s lymphoma may experience lymph node pain after what
Patients with Hodgkin’s lymphoma may experience lymph node pain after drinking alcohol.
what do B symptoms refer to
systemic symptoms of lymphoma
what are the B symptoms of lymphoma
fever
weight loss
night sweats
what are the additional non-specific symptoms
Fatigue
Itching
Cough
Shortness of breath
Abdominal pain
Recurrent infections
what is a critical diagnostic investigation for lymphoma
lymph node biopsy
what is the characteristic finding on a biopsy for Hodkin’s lymphoma
Reed-Sternberg cells
what are Reed-sternberg cells
large cancerous B lymphocytes with 2 nuclei and prominent nucleoli, giving them a cartoonish appearance of an owl face with large eyes
what classification system is used for Hodgkin’s and non-Hodgkin’s
the Lugano classification system
what does the Lugano classification emphasise and describe the simple version of it
It emphasises whether the affected nodes are above or below the diaphragm. A simplified version is:
Stage 1: Confined to one node or group of nodes
Stage 2: In more than one group of nodes but on the same side of the diaphragm (either above or below)
Stage 3: Affects lymph nodes both above and below the diaphragm
Stage 4: Widespread involvement, including non-lymphatic organs, such as the lungs or liver
what are the critical treatments for Hodgkin’s lymphoma
chemotherapy and radiotherapy
what may chemotherapy result in
infections, cognitive impairment, secondary cancers, and infertility
what does management of non-Hodgkin’s lymphoma involve
watchful waiting
chemotherapy
monoclonal antibodies
stem cell transplantation
radiotherapy
what type of cancer is myeloma
cancer affecting the plasma cells in the bone marrow
what are plasma cells
B lymphocytes, that produce antibodies
what does cancer in a specific type of plasma cell result in the production of
large quantities of a specific paraprotein or M protein which is an abnormal antibody or part of an antibody
what is multiple myeloma
where the myeloma affects multiple bone marrow areas in the body
what is MGUS
monoclonal gammopathy of undetermined significance
what does MGUS involve
production of a specific paraprotein without other features of myeloma or cancer
what does monoclonal refer to
identical copies or clones originating from a single cell.
what is MGUS
often an incidental finding in an otherwise healthy personb
what does smouldering myeloma involve
abnormal plasma cells and paraproteins but no organ damage or symptoms
it has a greater risk of progression to myeloma
what are B lymphocytes made up of and how are they arranged
complex molecules made up of heavy and light chains arranged in a Y shape
what are the five types of antibodies produced by B lymphocytes
A,G,M,D,E
what is myeloma
a cancer of a single type of plasma cell, with a genetic mutation that causes them to rapudly and uncontrollably multiply
what do plasma cells with a genetic mutation in myeloma produce
They produce a specific paraprotein (or M protein), which is an abnormal antibody (immunoglobulin) or part of an antibody (often the light chain). There is an abnormally high level of this paraprotein (paraproteinaemia).
what does the Bence Jones protein refer to
free light chains in the urine
what is the pneumonic used to remember the four key features of myeloma
CRAB
what does CRAB stand for
C – Calcium (elevated)
R – Renal failure
A – Anaemia
B – Bone lesions and bone pain
what is the most common complication of myeloma
anaemia
the cancerous plasma cells invade the bone marrow, resulting in suppression of the other blood cell lines, leading to anaemia, leukopenia, and thrombocytopenia
what type of anaemia is seen in myeloma
normocytic and normochromic
what does myeloma bone disease result from
increased osteoclast activity and suppressed osteoblast activity
what do osteoblasts and osteoclasts do
osteoblasts deposit bone and osteoclasts absorb bone
where are the common sites of myeloma bone disease
skull, spine, long bones and ribs
what are patches of thin bone described as
osteolytic lesions
what do the weak points in the bone lead to
pathological features for example a vertebral body in the spine may collapse or a long bone such as the femur may break under minimal force
what does increased osteoclast activity cause
calcium rebasoption from the bone into the blood resulting in hypercalcaemia
what are plasmacytomas
individual tumours formed by cancerous plasma cells
they can occur in the bones, replacing normal bone tissue or in the soft tissue
what are the various causes of renal impairment in patients with myeloma
Paraproteins deposited in the kidneys
Hypercalcaemia affecting kidney function
Dehydration
Glomerulonephritis (inflammation around the glomerulus and nephron)
Medications used to treat the condition
what is the normal plasma viscocity or internal friction in blood flow
between 1.3 and 1.7 times that of water
when does plasma viscocity increase
when there are more proteins in the bloof, such as the paraproteins found in myeloma
what are the issues that hyperviscocity syndrome may cause
Bleeding (e.g., nosebleeds and bleeding gums)
Visual symptoms and eye changes (e.g., retinal haemorrhages)
Neurological complications (e.g., stroke)
Heart failure
what presenting features that should raise suspicion of myeloma include
Persistent bone pain (e.g., spinal pain)
Pathological fractures
Unexplained fatigue
Unexplained weight loss
Fever of unknown origin
Hypercalcaemia
Anaemia
Renal impairment
what are the laboratory results seen in myeloma
FBC (anaemia or leukopenia in myeloma)
Calcium (raised in myeloma)
ESR (increased in myeloma)
Plasma viscosity (increased in myeloma)
U&E (for renal impairment)
Serum protein electrophoresis (to detect paraproteinaemia)
Serum-free light-chain assay (to detect abnormally abundant light chains)
Urine protein electrophoresis (to detect the Bence-Jones protein)
what is used to confirm the diagnosis of myeloma
bone marrow biopsy
what are the typical x ray findings seen in patients with myeloma
Well-defined lytic lesions (described as looking “punched-out”)
Diffuse osteopenia
Abnormal fractures
what is the name of the condition that refers to multiple lytic lesions seen in the skull on X ray
raindrop skull
is myeloma ever fully cured
myeloma takes a relapsing-remitting course and is never fully cured
what does treatment for myeloma usually involve (chemotherapy)
Bortezomib (a proteasome inhibitor)
Thalidomide
Dexamethasone
what is a treatment option given to fitter patients and may achieve a more extended period of remission
High-dose chemotherapy followed by a stem cell transplant is an option for fitter patients and may achieve a more extended period of remission
what are the two types of stem cell transplantation
Autologous (using the person’s own stem cells)
Allogeneic (using stem cells from a healthy donor)
what does management of myeloma bone disease involve
Bisphosphonates to suppress osteoclast activity
Radiotherapy for bone lesions can improve bone pain
Orthopaedic surgery to stabilise bones (e.g., by inserting a prophylactic intramedullary rod) or treat fractures
Cement augmentation (injecting cement into vertebral fractures or lesions) to improve spine stability and pain
what is pancytopenia
a condition in which there is a lower-than-normal number of red and white blood cells and platelets in the blood
what are the main causes of pancytopenia
megaloblastic anaemia, AML and aplastic anaemia
