Haematological Cancers Flashcards
What is myeloma?
A neiplastic disease of the plasma cells (grown up B lymphocytes which have turned into antibody producing cells)
What are the antibodies floating around in myeloma called.
Because it is a cancer of the plasma cells, which produce antibodies you will have lots of antibodies all of the same type, these are called monoclonal but specifically to myeloma they are called paraprotein.
What levels should you measure if someone has myeloma?
It is important to measure paraprotein levels.
What is a lymphoma and what are the two types?
Neoplastic disease of mature lymphocytes in lymphoid tissue, the two types are: hodgkins and non hodgkins lymphoma.
Where are lymphomas normally found?
Anywhere where the lymphoid tissue is found- gut, skin, MALT, lymph nodes.
What is acute leukaemia?
Neoplastic disease of the immature cells (blasts) in the bone marrow, can either be acute myeloid or acute lymphoid.
What is chronic leukaemia?
Neoplastic disease of mature WBC in the bone marrow, again can be myeloid or lymphoid.
What is myeloproliferative disease?
Group of neoplastic disorders which involve bone marrow cells which produce red blood cells, platelets and fibroblasts.
What are the clinical features of Hodgkin’s/ non hodgkins lymphoma?
Face- conjunctival pallor
Retinal haemorrhage
Pallor of mucous membranes
Enlarged lymph nodes
Skin- petichae, ecchymosis, palmar creases pallor
GI- early satiety, hepatosplenomegaly, para aortic, lymphadenopathy
MSK- bone pain
Other- anaemia, pancytopaenia, thrombocytopenia, weight loss, night sweats, malaise, fatigue
What is the staging of hodgkins/ non hodgkins lymphoma?
Stage 1- disease is confined to one lymph node or two contiguous lymph node groups
Stage 2- disease on one side of the diaphragm in two separate lymph node groups
Stage 3- disease on both sides of the diaphragm
Stage 4- extra nodal spread with diffuse or disseminated spread of one or more extralymphatic organs
Modifiers…
a= absence of constitutional symptoms
B= presence of B symptoms (fever, night sweats, weight loss)
C= if disease is extranodal or has spread from lymph nodes to adjacent tissue
X= if the largest deposit is >10cm in diameter or if the mediastinum is wider than 1/3 of the chest diameter on x ray
S= disease spread to spleen
What are the subtypes of Hodgkin’s lymphoma?
. Nodular sclerosing (60%) is the most common subtype
Typically young adults who have early supra-diaphragmatic presentations
Patients have a good prognosis
. Mixed cellularity (30%)
. Lymphocyte predominant (5%) best prognosis
. Lymphocyte depleted (5%) rare subtype with lots of reed Sternberg with only a few lymphocytes
.
What is the usual presentation of hodgkins lymphoma?
Usually painless lymphadenopathy above diaphragm
Can also get systemic symptoms- b symptoms ‘fevers, night sweats, weight loss’ and chronic pruritis
Systemic symptoms have a negative impact on prognosis
What are the most common extra nodal sites to be involved in hodgkins lymphoma?
. Spleen
. Lung
. Liver
. Bone marrow
What are the investigations done for a hodgkins lymphoma?
Careful history and clinical exam
ESR
FBC
LFTs
U&Es
ALP (elevated is non specific but may indicate bone involvement)
LDH (sig elevated is associated with a worse prognosis)
Abnormal liver function should prompt further evaluation with imaging and possible biopsy
Biopsy of an enlarged lymph node is vital for diagnosis, this should be an wide excision biopsy
Imaging should include a CXR and CT or MRI of the chest, abdomen or pelvis
PET imaging can be used to determine the extent of spread and for staging
Bone marrow aspirate and trephine should be considered because of the impact of positive biopsy on further imaging and treatment.
What is the treatment for Hodgkin’s lymphoma?
Stage 1-2a = radiotherapy
Stage 2b-4 = chemo
High dose chemo followed by stem cell teansplantation is the most effective treatment for patients who do not respond to standard chemo
What is the prognosis for hodgkins lymphoma?
90% of patients with small volume, early stage disease are cured with radiotherapy
40-60% with advanced are treated with chemo
What are the poor prognostic factors for Hodgkin’s lymphoma?
. B symptoms . Age >45 . Bulky mediastinal disease . Extranodal involvement . Low haematocrit (the ratio of the volume of red blood cells to blood) . High ESR . High levels of CD30 and soluble IL-2
What viruses are implicated in the pathogenesis of non Hodgkin’s lymphoma?
EBV (burkitts lymphoma)
HTLV-1 (adult T cell leukaemia/ lymphoma)
HHV 8 (kaposis sarcoma)
HCV
How does non hodgkins lymphoma present?
Low grade= painless, slowly progressive peripheral lymphadenopathy which sometimes waxes and wanes.
Spontaneous regression of large lymph nodes can occur which can cause them to be confused with infections
Intermediate/high grade= majority of patients have lymphadenopathy
40% extranodal involvement
B symptoms in about 40% of patients
How do patients with burkitts lymphoma present?
Large abdo mass and symptoms of bowel obstruction
What are the investigations for non hodgkins lymphoma?
Wide excision biopsy for diagnosis FBC ALP LFTs CXR CT of chest and abdomen PET imaging for staging LDH and beta 2 microglobulin HIV serology/HLTV1 serology based on histology
What is the treatment of hodgkins lymphoma?
radiotherapy
chemotherapy
steroids
high dose chemotherapy with a stem cell or bone marrow transplant
People with the rare nodular lymphocyte predominant type of Hodgkin lymphoma (NLPHL) may have a type of biological therapy called rituximab.
You will probably have a short course of chemotherapy if you have limited disease. Your doctor might then recommend radiotherapy to the affected lymph nodes. You might also have radiotherapy to your spleen or other lymph nodes.
You might just have radiotherapy to the affected lymph nodes if you have very early, localised disease and are not able to have chemotherapy for any reason.
Early nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) may not need any treatment. It is a slow growing cancer and your doctor may prefer to wait before giving you any treatment.
Advanced stage generally means that you have stage 2B, 3 or 4 Hodgkin lymphoma.
You are most likely to have chemotherapy with or without steroids. You may also have radiotherapy to particular groups of lymph nodes if they are very swollen (enlarged) or causing symptoms.
You might have high dose chemotherapy with a stem cell or bone marrow transplant, if your lymphoma comes back after treatment (relapses). Or your doctor might suggest treatment with a biological therapy drug called brentuximab.
Or you might have more chemotherapy or radiotherapy, depending on the treatment you have already had.
Sometimes Hodgkin lymphoma does not respond as well to initial treatment as your doctor would hope. You might have more treatment, for example, radiotherapy as well as chemotherapy. Or they may change your chemotherapy drugs, or give you the biological therapy drug brentuximab.
Or your doctor might suggest high dose chemotherapy treatment with a stem cell or bone marrow transplant.
What is rituximab?
Monoclonal antibody that targets the CD20 antigen found on the surface of more than 90% of B cell lymphomas. This is used as a single agent in the treatment of relapses low grade non Hodgkin’s lymphoma and is also used in combo with chemo for follicular, mantle cell and diffuse aggressive NHL
What is myeloma?
Cancer of the plasma cells, plasma cells are a type of B lymphocyte which produce antibodies, therefore cancer in a specific type of plasma cell results in large quantities of a single type of antibody being produced.
What is multiple myeloma?
This is where the myeloma affects multiple areas of the body
What is monoclonal gammopathy of undetermined significance?
This is when there is an excess of a single type of antibody or antibody components without other features of myeloma or cancer, it is often an incidental finding of an otherwise healthy individual, however individuals are often followed up routinely to monitor for progression.
What is the pathophysiology behind myeloma?
Neoplastic disease of plasma cells
Plasma cells are B cells of the immune system which have become activated to produce a certain antibody
They are called B cells because they are found in the bone marrow
Myeloma is a cancer of a specific type of plasma cell where there is a genetic mutation causing it to rapidly and uncontrollably multiply.
Antibodies are also called immunoglobulins
What are the different types of immunoglobulins and why is this significant in myeloma?
A, M, D, E, B, G
When you measure the immunoglobulins in a patient with myeloma, one of the types will be significantly raised, more than 50% of the time this is IgG.
What is a monoclonal paraprotein?
The single type of antibody which is produced by all the identical cancerous plasma cells in myeloma.
What is the bence jones protein?
Found in the urine of patients with myeloma, it is a subunit of the antibodies (light chains)
Why do you get anaemia in myeloma?
The cancerous plasma cells invade the bone marrow, bone marrow infiltration, causes suppression of the the development of other blood cell lines which leads to anaemia (low red cells), thrombocytopenia and neutropenia.
What is myeloma bone disease?
This occurs as a result of increased osteoclast activity and suppressed osteoblast activity
More than 80% of multiple myeloma patients develop bone problems during the course of their disease; 70% of these patients have bone loss in the spine.
Multiple myeloma upsets the osteoclast-osteoblast balance by uncoupling their functions. Myeloma cells produce osteoclast-activating factors, signaling osteoclasts to break down bone uncontrollably. At the same time, they prevent bone repair by inhibiting the formation of osteoblasts.
something to do with cytokines
Where is myeloma bone disease likely to occur?
Skull, spine, long bones, ribs
The abnormal bone metabolism is patchy, some areas of the bone become very thin whereas others remain normal, the patches where the bone is thin are known as osteolytic lesions. The weak parts of the bone lead to pathological fractures
All the osteoclast activity in myeloma bone disease results in calcium being reabsorbed from the bone and therefore leads to hypercalcaemia.
What are plasmacytomas?
These are individual tumours formed by cancerous plasma cells which people with myeloma can develop.
Plasmacytomas can occur in the bones, replacing normal bone tissue or outside bones un the soft tissues of the body.
Why can patients with myeloma develop renal impairment?
High levels pf immunoglobulins can block the flow through tubules
Hypercalcaemia impairs renal function
Treatments- bisphosphonates
Dehydration
Why do patients with myeloma have hyperviscosity?
Plasma viscosity increases when there are more proteins in the blood, in myeloma there are more immunoglobulins (proteins)
What is the problem with increased viscosity?
Easy bruising
Easy bleeding
Reduced/loss of sight due to vascular disease of the eye
Purple discolouration to the extremities (purplish palmar erythema)
Heart failure
What are the important features of myeloma that you should remember?
CRAB HAI C= calcium R= renal failure A= anaemia (normocytic, normochromic) B= bone lesions/pain H= hyper-viscosity A= amyloidosis I= infection
