Leukaemia and lymphoma Flashcards
Which cell line is usually affected when a person developed leukaemia?
- Usually Lymphoid
What can any haematological cell line turn at any number of stages in the system?
- Neoplastic (an abnormal new growth of tissues in animals; a tumour)
When in a haematological cell line is the malignancy potentially more aggressive?
- The earlier in the cell line
What is haematological malignancy caused by?
- DNA mutation
(usually translocation)
- Switches ‘off’ a tumour suppressor gene or swithches ‘on’ an oncogene
What is an oncogene?
- Any of various mutated genes that cause the transformation of normal cells into cancerous cells
What are 3 characteristics of cancer cells?
- Uncontrolled proliferation
- Loss of apoptosis
- Loss of normal functions/products
What does ‘acute’ mean?
- Very severe
- Happens suddenly
What does chronic mean?
- Can take many years to show
What is and example of acute lymphoid?
- Acute lymphoblastic leukaemia
What is an example of acute myeloid?
- Acute myeloid leukaemia
What are different types of chronic lymphoma? (4 points)
- Chronic lymphocytic leukaemia
- Hodgkin lymphoma
- Non-Hodgkin lymphoma
Multiple myeloma
What are lymphomas?
- Solid lumps of haematogenous cells
What is an example of chronic myeloma?
- Chronic myeloid leukaemia a
- myeloproliferative disorders
The two types of leukaemia are acute or chronic and they denote the clinical behaviour of the leukaemia. What does this mean?
- Is it going to be a rapid problem or a rumbling problem
What does lymphocytic, lymphoblastic or myeloid describe?
- The point in the cell lines or cell type at fault
What does lymphocytic mean?
- Looks like the cells they are supposed to be
What does lymphoblastic mean?
- Differentiation is so far up the line you can’t really tell what the cell is going to be
What des ‘blast’ mean?
- An immature cell
Which type of leukaemia is serious and life-threatening?
- Acute leukaemia
Leukaemia describes a group of cancers of the bone marrow which prevent normal manufacture of the blood and therefore result in what 3 things?
- Anaemia
- Infection (neutropenia)
- Bleeding (thrombocytopenia)
What is neutropenia?
- An abnormally low level of neutrophils in the blood. Neutrophils are WBC’s produced in the bone marrow that ingest bacteria. This is a serious disorder because it makes the body vulnerable to bacterial and fun gal infections
What is thrombocytopenia?
- An abnormal drop in the number of blood cells involved in forming blood clots. These cells are called platelets
What is meant by pathogenesis?
- The manner of development of a disease
What is the pathogenesis of leukaemia?
- Clonal proliferation
- Replacement of marrow
- Increasing marginalisation of productive normal marrow:
1. Marrow failure
2. Organ infiltration
What is the clinical presentation of leukaemia? (6 points)
- Anaemia (problems with carrying oxygen)
- Neutropenia (problems with infection)
- Thrombocytopenia (Problems with bleeding)
- Lymphadenopathy - neck lumps (may or may not be palpable)
- Splenomegaly/hepatomegaly - swollen abdomen
- Bone pain - especially in children (because bone marrow is trying to expand in the bone cavity)
What is lymphadenopathy?
- Neck lumps
- Disease of the lymph nodes
What is splenomegaly?
- Enlargement of the spleen
- Swollen abdomen
What is hepatomegaly?
- Enlargement of the liver
- Swollen abdomen
What are the progressive signs of anaemia? (4 points)
- Breathlessness
- Tiredness
- Easily fatigued
- Chest pain/angina
What is angina caused by?
- Caused when heart muscles receive insufficient oxygen-rich blood
What are the common signs of anaemia? (3 points)
- Pallor (an unhealthy pale appearance)
- Signs of cardiac failure (ankle swelling, breathlessness)
- Nail changes (brittle nails, koilonychia)
What is koilonychia?
- A condition that affects the shape of nails. They curve inward and look like a spoon
Neutropenia is related to infections associated with portals of entry into the body. What are examples of these? (5 points)
- Mouth
- Throat (tonsillitis, pharyngitis)
- Chest (bronchitis, pneumonia)
- Skin (impetigo, cellulitis)
- Perianal (thrush, abscesses)
What is pneumonia?
- A swelling of the tissue in one or both of the lungs. It is usually caused by a bacterial infection
What is impetigo?
- Bacterial infection of the surface of the skin
- Usually due to bacteria Staph. aureus
- (common in young children)
Neutropenia allows the reactivation of latent infections. What does this mean?
- Infections that stay in the body waiting for the ability to act again
What can neutropenia lead to in relation to infections?
-leads to increased severity and frequency of infections and can rapidly lead to systemic infection
What is a systemic infection?
- The cause of a systemic infection comprises of bacteria or virus
- The main characteristic of such infection is that it affects the bloodstream of an individual, with the result of that being that the symptoms spread to the whole of the body
What are the symptoms of neutropenia? (2 points)
- Recurrent infection (as don’t have the immune response to contain it)
- Unusual severity of infection
What are the signs of neutropenia? (3 points)
- Unusual patterns of infection and rapid spread
- Will respond to treatment but recur
- Signs of systemic involvement - fever, rigors, chills
When we do investigations on someone with neutropenia what do we usually find is the cause of infection?
- Unusual pathogens, usually bacterial
What are the common symptoms of bleeding caused by thrombocytopenia? (4 points)
- Bruising easily or spontaneously
- Minor cuts failing to clot
- Gingival bleeding or nose bleeds (spontaneous)
- Menorrhagia (excessive menstruation)
What is menorrhagia?
- Excessive menstruation
What are the common signs of bleeding caused by thrombocytopenia? (4 points)
- Bruising
- Petechiae (red splodges)
- BOP (bleeding on probing)
- Bleeding/bruising following procedure
What is petechiae?
- Red splodges - caused by bleeding into the skin
What type of blood cell does acute lymphoblastic leukaemia affect?
- White blood cells
What is the peak age for someone to develop acute lymphoblastic leukaemia?
- 4 but does occur in adults
How many people a year are affected by acute lymphoblastic leukaemia?
- 25 per 1,000,000 people per year
How long does it take for acute lymphoblastic leukaemia to develop?
- Develops over days or weeks
How does acute lymphoblastic leukaemia present?
- Will present as many non-specific symptoms
When someone had acute lymphoblastic leukaemia, they are in a catabolic state. What symptoms does this lead to? (3 points)
- Fever
- Sweats
- Malaise (general feeling of discomfort, illness or unease whose exact cause is difficult to identify)
Lymphadenopathy is common in people with acute lymphoblastic leukaemia. What is lymphadenopathy?
- A disease affecting the lymph nodes
Which groups of people have a better prognosis when they have acute lymphoblastic leukaemia?
- Better for younger patients and females
- Girls aged 2-12 do best
What percentage of children with acute lymphoblastic leukaemia are cured?
- Greater than 80%
What is the difference between acute myeloid leukaemia and acute lymphoblastic leukaemia?
- AML is a cancer that affects the myeloid line of blood cells. ALL is a cancer that affects the white blood cells by producing excessive lymphoblast’s. AML occurs when a myeoblast goes through genetic changes and freezes in the immature stage. ALL occurs when malignant, immature lymphoblast’s multiply in the bone marrow and hinder the production of other normal blood cells
How many cases of acute myeloid leukaemia are there per year?
- 25 per 1 million per year
At what age does acute myeloid leukaemia occur?
- AML occurs at any age but is more common in the elderly
What is the clinical representation of AML like in comparison to ALL?
- Similar clinical representation
What is the prognosis of a patient with acute m yeloid leukaemia?
- 30-40% of 70 y/o’s but improving
What is another name for chronic lymphocytic (lymphoid) leukaemia?
- B-cell clonal lymphoproliferative disease
What age of the population is normally affected by chronic lymphocytic leukaemia?
- Older adults, peak age >70 years
How many people per year are affected by chronic lymphocytic leukaemia?
- 70 per 1 million (commonest leukaemia)
What is the ratio of males to females who get chronic lymphocytic leukaemia?
- M:F = 2:1
Chronic lymphocytic leukaemia is mostly asymptomatic. How is it usually discovered?
- On routine blood tests by accident
Chronic lymphocytic leukaemia sometimes has an occasional blast transformation. What does this lead to?
- An aggressive form
What is the progression of chronic lymphocytic leukaemia?
- Slow progression, may not require treatment
What cells does chronic myeloid leukaemia increase in numbers?
- Neutrophils and their precursors
What percentage of people with chronic myeloid leukaemia have the ‘Philadelphia’ chromosome and what is it?
- 95%
- An abnormality of chromosome 22 in which part of chromosome 9 is transferred to it
How many cases per year are there of chronic myeloid leukaemia?
- 15 cases per 1 million per year
What is the peak age for someone to develop chronic myeloid leukaemia?
- Peak age is 50-70 y/o but can occur at any time
Does chronic myeloid leukaemia affect more males or females?
- Slight male preponderance
What us the clinical presentation of chronic myeloid leukaemia? (6 points)
- Fatigue
- Weight loss
- Sweating
- Anaemia
- Bleeding
- Splenomegaly
What is lymphoma?
- Clonal proliferation of lymphocytes arising in a lymph node or associated tissues
- Solid tumour but some cells in blood
How many cases of lymphoma are there per year?
- 200 cases per 1 million per year + increasing
What are the 2 types of lymphoma?
- Hodgkin lymphoma (Hodgkin’s disease)
- non-Hodgkin lymphoma
What is the ratio of cases of non-Hodgkin lymphoma compared to Hodgkin lymphoma?
- MHL more common than HL = 6:1
Are the behavioural and clinical features of Hodgkin and non-Hodgkin lymphomas similar or different?
- Different
What is staging of lymphomas?
- Depends on where you have lumps of lymphoid cells
- These stages will inform the prognosis
1. no. of nodes involved and site
2. Extra-nodal involvement
3. Systemic symptoms
What do you need to use to detect the staging of lymphomas?
- Requires imaging - CT, PET/CT or MRI
What is staging of lymphomas important in predicting?
- The prognosis and deciding treatment
What is a stage 1 lymphoma?
- Single lymph node region or single extralymphatic site
What does extralymphatic site mean?
- A site other than lymph nodes and other lymphatic structures
What is a stage 2 lymphoma?
- Two or more sites, same side of diaphragm or a extralymphatic site close to or touching the lymph nodes
What is a stage 3 lymphoma?
- Both sides of the diaphragm or spleen or contiguous extralymphatic site
- If involves spleen then it becomes a stage 3
What is a stage 4 lymphoma?
- Diffuse involvement of extralymphatic sites +/- nodal disease
What is the peak incidence age of people who develop Hodgkin lymphomas?
- 15-40 y/o
- (younger persons disease)
What is the male to female ratio of people with Hodgkin lymphoma?
- M>F = 2:1
What is the clinical presentation of Hodgkin lymphomas? (6 points)
- Painless lymphadenopathy - typically cervical, fluctuates in size (pain with alcohol notable)
- Fever, night sweats, weight loss, itching
- Infection
What is the cure prognosis for Stage 1 and 2 Hodgkin’s lymphomas?
- > 90%
What is the cure prognosis for stage 3 and 4 Hodgkin lymphomas?
- 50-70%
What age group does less well then they have Hodgkin lymphomas?
- Older people
What percentage of non-Hodgkin lymphomas are B-cell and T-cell?
- B-cell (85%)
- T-cell (15%)
At what age are people more likely to develop non-Hodgkin’s lymphomas?
- Any age (more indolent in elderly - disease progresses more slowly in the elderly)
What is the aetiology of non-Hodgkin lymphomas? (3 points)
- Microbial factors strongly implicated
- Autoimmune disease (Sjogren’s syndrome, Rheumatoid arthritis)
- Immunosuppression (AIDS, post-transplant)
What does non-Hodgkin lymphoma present like? (4 point s)
- Lymphadenopathy (may be invisible)
- Extra-nodal disease more common (oropharyngeal involvement - Waldeyer’s ring)
- Symptoms of marrow failure
- Constitutional symptoms less common (symptoms indicating a systemic effect of a disease)
What is the prognosis of non-Hodgkin’s lymphoma? (3 points)
- > 50% will relapse after treatment
- Aggressive disease so poor prognosis untreated but noteably often responds better to treatment
- Indolent disease is hard to cure
What is a multiple myeloma?
- Malignant proliferation of plasma cells
What is the incidence of multiple myelomas per year?
- 50 per million per year
What are the features of multiple myelomas? (3 points)
- Monoclonal paraprotein in blood and urine
- Lytic bone lesions -> pain and fracture
- Excessive plasma cells in bone marrow -> marrow failure
What is the mean age at diagnosis of multiple myelomas?
- 70 years
Are males or females more prone to developing multiple myelomas?
- Males
Are black people or white people more prone to developing multiple myelomas?
- Black people
What 4 things can commonly be caused by multiple myelomas?
- Infection
- Bone pain
- Renal failure
- Amyloidosis (antibodies that are produced in excess amount that collect in places in the body that causes them to be enlarged)
What are the possible treatments of haematological malignancies? (5 points)
- New drugs coming out all the time
- Chemotherapy
- Radiotherapy
- Monoclonal antibodies - increasingly important
- Haemopoietic stem cell transplantation
What are the 4 stages of treating a haematological malignancy?
- Induction (intense chemotherapy where they blast all the bad cells out of the body)
- Remission (Don’t have any acute problems but of you do nothing it is likely they will come back again)
- Maintenance and consolidation (Need to keep things at bay)
- Relapse (depends upon whether you can make the treatment work in a away that reaches all leukemic cells in the body - prevents chance of relapse)
Supportive therapy is very important in the treatment of haematological malignancies. What are examples of these? (6 points)
- Nutrition
- Psychological and social support
- Prevention and treatment of infection
- Managing symptoms of therapy side effects e.g. anti-emetics
- Correcting marked blood component deficits
- Pain control
What are anti-emetic drugs used for?
- Group of drugs typically used to prevent and control severe nausea, vomiting and motion sickness
Which cells are targeted with chemotherapy?
- Cells with high turnover rate targeted but will also kill off cells in other tissues that are replicating rapidly but that are not leukemic cells e.g. gut cells, oral mucosa
- Responsible for many unwanted effects in normal high turnover tissues
What are common side effects of chemotherapy? (4 points)
- Hair loss
- Nausea
- Vomitting
- Tiredness
What is there a long term risk of in patients who have survived chemotherapy?
- Oncogenesis (the formation and development of tumours)
When giving radiotherapy there is a cytotoxic effect of ionising radiation, where adjacent healthy tissue will also be irradiated. How is the effect of this minimised?
- Using complex spatial positioning, targeting and dosing techniques
In radiotherapy where is the bean directed from?
- Outside the body
What does radiotherapy carry a risk for?
- Inducing late cancers - Can cause damage to the DNA of stem cells and this can form new cancers later in life
Monoclonal antibodies are produced in artificially large quantities. What is specific about them?
- They are produces to specific cancer cell antigens
- Good at targeting specific cell lines
Are monoclonal antibodies expensive to produce and deliver?
- Yes
What do the drug names of monoclonal antibodies end in?
- Names end in ‘-mab’ e.g. infliximab
If getting a haemopoietic stem cell transplant from a live donor in an ‘allogenic’ way. What does this mean?
From:
- A relative usually a sibling (close genetic match) OR
- A stranger who has been matched
If getting a haemopoietic stem cell transplant from a live donor in an ‘autologous’ way. What does this mean?
- From the patient
If a patient has a haemopoietic stem cell transplant, they require total body irradiation. What does this mean?
- Eradicate malignant cells and host marrow - ‘clean sheet’
If a patient is getting a haemopoietic stem cell transplant, where would you usually get the stem cells from?
- From the blood rather than bone marrow
Haemopoietic stem cell transplants are high risk procedure with 10% mortality risks. What are 3 reasons for this?
- Life-threatening infection
- Graft versus host di sease
- Graft failure and total marrow failure
