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7. Haematology > Multiple Myeloma > Flashcards

Multiple Myeloma Flashcards

1
Q

What is myeloma?

A

Malignancy of plasma cells leading to progressive bone marrow failure. It is associated with production of characteristic paraprotein, bone disease and renal failure.

Antibody produced = monoclonal paraprotein!! - KNOW THIS

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2
Q

What cell line is affected by multiple myeloma?

A

Plasma cells - malignant clonal expansion - produce excessive amounts of one type of Ig/Ig fragment (monoclonal element) in the serum or urine.

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3
Q

Explain the pathophysiology of myeloma.

A
  1. Genetic mutation of a specific type of plasma cell, causing it to rapidly and uncontrollably multiply.
  2. One of the types of Ig will be significantly high
    (More than 50% of the time this is IgG).
  3. This single type of antibody that is produced by all the identical cancerous plasma cells can be called a monoclonal paraprotein. This means a single type of abnormal protein.
  4. The “Bence Jones protein” that can be found in the urine of many patients with myeloma is actually a part (subunit) of the antibody called the light chains.
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4
Q

Give 3 symptoms of myeloma.

A
  1. Tiredness.
  2. Bone/back pain.
  3. Infections.
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5
Q

Give 4 signs of myeloma.

A

CRAB!

  1. Calcium is elevated.
  2. Renal failure.
  3. Anaemia.
  4. Bone lesions.
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6
Q

Why is calcium elevated in myeloma?

A

There is increased bone resorption and decreased formation meaning there is more calcium in the blood.

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7
Q

What kind of anaemia is seen in patients with multiple myeloma?

A

Normochromic normocytic.

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8
Q

Why might someone with myeloma have anaemia?

A

The bone marrow is infiltrated with plasma cells. Consequences of this are anaemia, infections and bleeding.

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9
Q

Why are patients with myeloma susceptible to recurrent infections?

A

There is a reduction in polyclonal immunoglobulin levels.

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10
Q

Why might someone with myeloma have renal failure?

A

Due to light chain deposition.

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11
Q

How is multiple myeloma classified?

A

On a spectrum, according to M protein (a monoclonal component) and presence of tissue/organ involvement:

  1. MGUS (monoclonal gammopathy of unknown significance)
    - M-protein <30g/dL
    - BM clonal cells <10%
  2. Smouldering (asymptomatic) myeloma
    - M-protein >30
    - BM cloncal cells >10%
    - BUT no tissue/organ involvement
  3. Active (symptomatic) myeloma
    - M-protein >30
    - BM cloncal cells >30%
    - And CRAB features.
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12
Q

What are the 3 main associations of multiple myeloma?

A

1) Osteolytic bone disease + hypercalcaemia
2) Anaemia (due to accumulation of plasma cells in BM)
3) Renal disease

Most common haematological malignancy!
Mean age 60yrs

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13
Q

What disease often precedes myeloma?

A

Monoclonal gammopathy of undetermined significance (MGUS).

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14
Q

What is MGUS?

A

A common disease with paraprotein present in the serum but no myeloma. Often asymptomatic. <10% plasma cells in the bone marrow.

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15
Q

Give an example of smouldering myeloma.

A

Waldenstrom’s macroglobulinemia is a type of smouldering myeloma where there is excessive IgM specifically.

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16
Q

In extreme cases, patients with myeloma can present with blurred vision, gangrene and bleeding. What is the pathology behind this?

A

Paraproteins form aggregates in the blood and change the viscosity.

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17
Q

What are the diagnostic criteria for myeloma?

A

1) Monoclonal protein band on serum/urine electrophoresis
2) Increased plasma cells on bone marrow biopsy
3) Evidence of end organ damage (hypercalcaemia, renal failure, anaemia)

18
Q

In order to make a diagnosis of myeloma, there must be evidence of mono-clonality. What is mono-clonality?

A

Abnormal proliferation of a single clone of plasma cell leading to immunoglobulin secretion and causing organ dysfunction especially to the kidney.

19
Q

What initial investigations might you do in suspected myeloma?

A
  1. FBC (low white blood cell count in myeloma)
  2. Calcium (raised in myeloma)
  3. ESR (raised in myeloma)
  4. Plasma viscosity (raised in myeloma)

If any of these are positive or myeloma is still suspected, do an urgent serum protein electrophoresis and a urine Bence-Jones protein test.

20
Q

What investigations might you do to diagnose myeloma?

A
  1. Blood film.
  2. Bone marrow aspirate and trephine biopsy.
  3. Serum Urine/Protein Electrophoresis (Gold standard!!)
  4. Whole body MRI
  5. Whole body CT
  6. Skeletal survey (X-ray images of the full skeleton)
  7. Chromosomal abnormalities.

BLIP:
Bence-Jones protein urine electrophoresis
Serum free Light chain assay
Serum Ig’s
Protein electrophoresis

21
Q

How is myeloma bone disease usually assessed?

A

X-ray.

22
Q

In approximately 2/3 of people with myeloma, what might their urine contain?

A

Immunoglobulin light chains with kappa or lamda lineage.

23
Q

What would you expect to see on the blood film taken from someone with myeloma?

A

Rouleaux formation (aggregations of RBC’s).

24
Q

What are you looking for on a bone marrow biopsy taken from someone with myeloma?

A

Increased plasma cells.

Plasma cells infiltrate >10% (minor) or >30% (major)

25
Q

What are you looking for on serum/urine electrophoresis in a patient with myeloma?

A

Monoclonal protein band.

Paraprotein spike.
Bence Jones (light chain) proteins in urine.

26
Q

What are you looking for on an X-ray taken from someone with myeloma?

A
  1. Punched out lesions
  2. Lytic lesions
  3. “Raindrop skull” caused by many punched out (lytic) lesions throughout the skull that give the appearance of raindrops splashing on a surface
27
Q

What is the treatment for MGUS and asymptomatic myeloma?

A

Watch and wait.

28
Q

Describe the treatment for symptomatic myeloma.

A

Chemotherapy, analgesia and bisphosphonates.

Radiotherapy and bone marrow transplant can also be done.

29
Q

What chemotherapy regime is used in patients with myeloma?

A

VAD or CTD.

V- Vincristine
A - Adriamycin (Doxorubicin)
D - Dexamethasone

C - Cyclophosphamide
T - Thalidomide
D - Dexamethasone

30
Q

How would you manage multiple myeloma?

A

Treat complications:
- Bone disease: bisphosphonates + analgesics
- Anaemia: blood transfusion/EPO
- Spinal cord compression: dexamethasone
- Hyperviscosity (reduced cognition/blurred vision): plasmapheresis
- AKI: rehydration/ preserve good hydration
- Infection: antibiotics + pneumonia/flu vaccine

Transplant candidate:
- Thalidomide or velcade (bortezomib) based induction + dexamethasone + DVT prophylaxis (aspirin 75mg OD) + autologous/allogeneic stem cell transplant

MGUS - Monitor closely with urine/serum electrophoresis 6 monthly

31
Q

Management of myeloma bone disease.

A
  1. Bisphosphonates
    - These suppress osteoclast activity.
  2. Radiotherapy to bone lesions
    - Can improve bone pain.
  3. Orthopaedic surgery
    - Can stabilise bones (e.g. by inserting a prophylactic intramedullary rod) or treat fractures.
  4. Cement augmentation
    - Involves injecting cement into vertebral fractures or lesions and can improve spine stability and pain
32
Q

Give 3 complications of myeloma.

A
  • Hypercalcaemia of malignancy.
  • Spinal cord compression.
  • Hyperviscosity.
  • Acute renal failure.
33
Q

Suggest 3 ways in which multiple myeloma can lead to AKI or myeloma renal disease.

A
  1. Deposition of light chain.
    - High levels of immunoglobulins (antibodies) can block the flow through the tubules.
  2. Hypercalcaemia.
  3. Hyperuricaemia.
  4. Dehydration.
  5. Medications used to treat the conditions such as bisphosphonates can be harmful to the kidneys
34
Q

Give a risk factor for spinal cord compression.

A

Any malignancy that can cause compression e.g. bone metastasis.

35
Q

Describe the presentation of spinal cord compression.

A
  1. Back pain.
  2. Weakness in legs.
  3. Inability to control bladder.
  4. Spastic paresis.
  5. Sensory level.
36
Q

Describe the management of spinal cord compression.

A
  1. Bed rest.
  2. High dose steroids.
  3. Analgesia.
  4. Urgent MRI of the whole spine.
37
Q

What is hyperviscosity syndrome?

A

Increase in blood viscosity usually due to high levels of immunoglobulins.

38
Q

Give 2 consequences of hyperviscosity syndrome.

A
  1. Vascular stasis.
  2. Hypoperfusion.
39
Q

Describe the presentation of hyperviscosity syndrome.

A
  1. Mucosal bleeding.
  2. Visual change.
  3. Neurological disturbances.
  4. Breathlessness.
  5. Fatigue.
40
Q

What investigations might you do in someone who you suspect has hyperviscosity syndrome?

A
  1. FBC and blood film; look for rouleaux formation.
  2. U&E.
  3. Immunoglobulins.
41
Q

What is the treatment for hyperviscosity syndrome?

A
  1. Keep hydrated!
  2. Avoid blood transfusion.
  3. Treat the underlying cause.

7. Haematology (15 decks)

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