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Yr4: Cancer Care > Myeloma > Flashcards

Myeloma Flashcards

1
Q

What is a paraprotein? (also referred to as monoclonal protein or M protein)

What are paraproteinaemias?

A
  • Paraproteins are monoclonal proteins that are produced by a clonal population of plasma cells
  • Paraproteinaemias are a group of disorders in which a clonal population of plasma cells produce a clonal population of paraproteins or light chains
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2
Q

Why is paraproteinemia a problem?

A
  • Hyperviscosity
  • Cause end organ damage (aim of treatment is to prevent irreversible end organ damage)
  • Immunosuppression
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3
Q

What is myeloma?

What is multiple myeloma?

Is it common?

A
  • Cancer of plasma cells (type of B lymphocyte that produce antibodies); the cancer is in a specific type of plasma cell resulting in large quantities of either a paraprotein or light chain being produced
  • Multiple myeloma is when myeloma is affecting multiple areas of body
  • Rare, 1% of all cancers
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4
Q

What is monoclonal gammopathy of undetermined significance (MGUS)?

A
  • Excess of monoclonal plasma cells and monoclonal paraprotein or light chain, not high enough to meet criteria for myeloma, without other features of myeloma/symptoms
  • Often incidental finding
  • Significance is unclear; it might progress to myeloma so pts are often followed up
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5
Q

What is smouldering myeloma? (also known as asymptomatic myeloma)

A
  • Progression of MGUS; call it smouldering myeloma when levels of plasma cells and paraprotein or light chain high enough to meet myeloma criteria but pt has not got symptoms.
  • Pre-malignant and more likely to progress to myeloma than MGUS
  • Example is Waldenstrom’s macroglobulinaemia

If paraprotein and plasma cells high enough to meet myeloma criteria but have no symptoms then it’s smouldering/asymptomatic myeloma. Treatment is watch & wait and treat when starting to develop early organ damage.

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6
Q

What is median age of presentation of myeloma?

A

70yrs

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7
Q

Discuss pathophysiology of myeloma, include:

  • What cancerous cells produce
  • How myeloma causes pancytopenia, bone disease, renal disease & hyperviscosity
A
  • Genetic mutation causes plasma cells to rapidly and uncontrollably multiple
  • Plasma cells produce one single type of antibody (immunoglobulin)
  • The single type of antibody that is produced by the identical cancerous plasma cells are called monoclonal paraproteins (meaning single type of abnormal protein)
  • >50% of time it is an IgG immunoglobulin

In regards to explaining signs & symptoms:

  • Invades bone marrow will get anaemia, thrombocytopenia, leucopenia
  • Myeloma cells produce chemical signals which increase osteoclast activity and suppress osteoblast activity causing bone resorption (leading to myeloma bone disease)
  • Renal disease occurs due to lots of factors: paraproteins can block tubules, hypercalcaemia impairs renal function, dehydration can occur, medications e.g. bisphosphonates can damage kidneys
  • Paraproteins increase plasma viscosity
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8
Q

What are some common places for myeloma bone disease?

A
  • Skull
  • Spine
  • Long bones
  • Ribs
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9
Q

State some risk factors for myeloma

A
  • Older age
  • Male
  • Black african ethnicity
  • Family history
  • Obesity
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10
Q

When thinking about symptoms and signs of myeloma we can think of it as affecting 4 organs/parts of body; state these

A
  • Bone marrow
  • Bone
  • Kidneys
  • Plasma- hyperviscosity
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11
Q

Describe signs & symptoms of myeloma

*HINT: CRABBIH

A
  • HyperCalcaemia
    • Constipation, nausea, anorexia, confusion
  • Renal impairment
    • Dehydration, increased thirst
  • Anaemia
    • Fatigue, SOB, palpitations, dizziness, pallor, cold extremities
  • Bleeding & bruising
  • Bones
    • Bone pain (particularly back), fractures
  • Infections
  • Hyperviscosity
    • Bleeding, bruising, reduced or loss of sight, purplish palmar erythema, heart failure
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12
Q

Why are myeloma patients susceptible to infections?

A
  • Abnormal production of clonal immunoglobulins leads to decreased numbers of other immunoglobulins
  • Immunoparesis of unaffected immunoglobulins
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13
Q

What are plasmocytomas?

A
  • Tumours made up of cancerous plasma cells
  • Can occur in bones (and hence worsen myeloma bone disease as replacing normal bone tissue) or in soft tissues of body
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14
Q

What initial investigations do NICE suggest if you suspect myeloma? For each state why you are doing it/what you might find

A
  • FBC: low WCC, low HB, low platelets
  • Calcium: raised due to bone resorption
  • ESR: raised
  • Plasma viscosity: raised
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15
Q

What further investigations do NICE recommend if myeloma is still suspected following initial investigations? For each state why you are doing it/what you might find

A

Cannot exclude multiple myeloma with just one investigation hence must do multiple:

  • Bence-Jones protein in urine: positive (not as commonly used now as we can now measure light chains in the blood instead)
  • Serum light chain assay: present
  • Serum immunoglobulins/serum protein elecotrophoresis: check for paraprotein
  • Beta 2 microglobulin: s**ignificantly elevated levels of beta 2 microglobulin can be found in lymphoproliferative disorders such as monoclonal gammopathies of immunoglobulin G (IgG) (multiple myeloma), malignant lymphomas, and chronic lymphocytic leukemia. Marker of tumour load.
  • Bone marrow biopsy aspiration & trephine: needed to confirm diagnosis. Monoclonal plasma cells raised. Aspirate sent for morphology (count plasma cells), flow cytometry/immunophenotyping to check for clonality & cytogenetics. Trephine tissue sample sent to histopathology to look for plasma cells
  • U&Es: assess for renal failure e.g. raised urea, raised creatine
  • Imaging to assess for bone lesions- only require one; here is order of preference:
    1. Whole body MRI
    2. Whole body CT
    3. Skeletal survery
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16
Q

What would you see on blood film of myeloma pt?

A

Rouleaux formation

17
Q

Why might a skeletal survey be normal in myeloma?

A

Would need to lose quite a lot of bone mass to see a lytic lesion on plain radiograph

*PET CT/MRI more sensitive so can pick up early lesions

18
Q

Why might a bone scan be normal in myeloma?

A

It is osteoclastic activity in myeloma

19
Q

What might you find on x-ray of pt with myeloma?

A
  • Raindrop skull
  • Lytic lesions
  • Punched out lesions
20
Q

What is the Bence Jones protein?

A

Monoclonal immunoglobulin light chains found in urine (and plasma) of pts with myelomas (and some other lymphoid malignancies)

21
Q

Discuss when you would refer someone via 2WW for suspected myeloma

A
22
Q

Discuss the management of myeloma

A

Aim is to control disease as it usually takes relapsing and remitting course; currently deemed incurable. Each remission will be shorter as clone adapts. Treatment aims to reduce amount of the abnormal clone to in turn reduce paraprotein production. Clone will then be dormant in bone marrow but will eventually start expanding. When it does, we start the next line drug. It’s the paraprotein that does the damage. Management via MDT:

Generic Management

  • Induction therapy: centred around reducing plasma cell clone to reduce paraprotein using chemotherapy (e.g. Velcade) & dexamethasone
  • Autologous stem cell transplant (after induction treatment these will be good quality stem cells with reduced amount of clone; harvest and store these then put back in after pt had high dose chemotherapy)
  • Maintain on immunomodulators e.g. revlimid
  • Other aspects of management: analgesia, vaccinations, immunoglobulin replacement therapy, EPO analogues, RBC transfusion, platelet transfusion

Management of myeloma bone disease

  • Bisphosphonates
  • Radiotherapy to bone lesion (to help with pain)
  • Orthopaedic surgery (stabilise bones, treat fractures… may have cement augmentation- inject cement into vertebral fractures or lesions)
23
Q

What is an autologous stem cell transplant?

A

An autologous stem cell transplant is used after high dose chemotherapy administration which targets stem cells. It involves the removal of a patient’s own stem cells prior to high dose chemotherapy, which are then replaced after chemotherapy. This is different from Allogenic stem cell transplantation where stem cells are sourced from HLA matching donors. Allogenic stem cell transplantation is currently only used as part of clinical trials when treating multiple myeloma.

24
Q

State some potential complications of myeloma

A
  • Pain
  • Renal failure
  • Anaemia
  • Hypercalcaemia
  • Infection
  • Pathological fractures
  • Spinal cord compression (due to tumour tissue or vertebral collapse due to erosion of vertebrae)
  • Hyperviscosity syndrome
25
Q

For Waldenstrom macroglobulinemia (also known as lymphoplasmacytoid lymphoma) discuss:

  • What it is
  • Age of presentation
  • Signs & symptoms
  • Management
A
  • Haematological malignancy in which there is a raised number of lymphoplasmacytic cells (a type of B cell) that produce large amount IgM/paraprotein; causes blood to become more viscous
  • Median age of onset is 70yrs
  • Some patients may not have any symptoms but they may also present with hyperviscosity symptoms e.g. headaches, epistaxis, visual disturbance) but may also present with weight loss, lethargy, anaemia symptoms, lymphadenopathy, Raynaud’s, parasthesia in extremities, balance problems (protein can cause nerve damage)
  • It develops slowly so many pts don’t need treatment for months or years and are just monitored; may need treatment when symptoms start to cause problems, IgM is increasing, decrease in blood counts etc… Treatment may be immunotherapy alone (e.g. rituximab) if low symptom burden or combination of immunotherapyand chemotherapy if higher symptom burden. May also have stem cell transplants, blood transfusions and plasmapheresis/plasma exchange (to thin the blood)
26
Q

Which paraproteinemia’s are most likely to cause hyperviscosity and why?

What is the management of hyperviscosity?

A
  • IgM (e.g. Waldenstrom’s macroglobulinaemia) as IgM is biggest
  • Management options:
    • Control paraproteins by giving chemo
    • Plasmapheresis (not done as often now as not many patients can tolerate such large volume)
27
Q

If you see IgM paraproteinemia, what disease should you be thinking of?

A

Lymphoproliferative diseases e.g.

  • CLL
  • Waldenstrom’s macroglobulinaemia

*So do you usual myeloma history CRABIH (as can rarely get IgM myeloma) AND include B symptoms

28
Q

Why might a bone scan be normal in myeloma?

A

It is osteoclastic activity in myeloma

Yr4: Cancer Care (19 decks)

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