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Clinical lectures: Yr2 > Multiple Myeloma > Flashcards

Multiple Myeloma Flashcards

1
Q

What is a paraprotein?

A

Monoclonal antibody that arises from a clone of lymphocytes or plasma

Paraproteins occur when plasma cells make the same antibody in response to a trigger, causing a monoclonal increase in globulins.

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2
Q

How do normal plasma cells behave compared to paraprotein-producing plasma cells?

A

Normal plasma cells make different antibodies, causing a polyclonal increase in globulins.

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3
Q

What is the main investigation for paraproteins?

A

Serum protein electrophoresis

This involves applying a plasma drop to a gel strip with an electric current to separate proteins with different charges.

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4
Q

What does an additional band on the serum protein electrophoresis graph indicate?

A

The monoclonal ‘M’ component

This band is abnormal and not present in a normal individual.

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5
Q

What is the purpose of the immunoassay in paraprotein investigation?

A

Detects free light chains in serum

It uses an antibody against the surface of the light chain that binds to the heavy chain, so bound light chains aren’t measured.

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6
Q

What does the ratio of serum lambda to kappa light chains indicate?

A

Paraproteinaemia

Paraproteins only make one type of light chain, leading to an excess of one type.

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7
Q

What does a positive result for Bence-Jones protein in urine indicate?

A

Multiple myeloma or malignant lymphomas

It is also used to detect primary amyloidosis.

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8
Q

What is multiple myeloma?

A

Malignant cancer due to overproliferation of plasma cells in the bone marrow.

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9
Q

What is the median diagnostic age for multiple myeloma?

A

60-65 years old.

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10
Q

Is multiple myeloma common in children?

A

No, it does not occur in children.

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11
Q

What are the hallmark symptoms in the CRAB criteria for end-organ damage in multiple myeloma?

A

The 4 hallmark symptoms are:
* Hypercalcaemia
* Renal failure
* Anaemia
* Bone lesions.

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12
Q

What causes hypercalcaemia in multiple myeloma?

A

Bone remodelling.

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13
Q

What causes renal failure in multiple myeloma?

A

Tubular damage from light chain deposition and other factors like NSAIDs and hypercalcaemia.

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14
Q

What causes anaemia in multiple myeloma?

A

Bone marrow replacement and renal damage decreasing EPO synthesis.

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15
Q

What causes bone lesions in multiple myeloma?

A

Activation of osteoclasts and inhibition of osteoblasts due to OPG and RANKL production.

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16
Q

What additional complications do patients with multiple myeloma face?

A

Increased risk of infections and spinal cord compression due to plasmacytomas.

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17
Q

What is a common presentation symptom for patients with multiple myeloma?

A

Back pain, height loss, kyphosis due to vertebral body collapse.

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18
Q

What investigation shows an increase in plasma cells in multiple myeloma?

A

Bone marrow aspirate.

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19
Q

What will a bone marrow aspirate or trephine show in myeloma?

A

Increase in bone marrow plasma cells by at least 10%

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20
Q

What imaging techniques can show lytic lesions in myeloma?

A

X-ray, CT, MRI, PET scans

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21
Q

Where are lytic lesions most commonly found in myeloma?

A

In long bones and skull

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22
Q

Why should patients with myeloma be assessed urgently?

A

They are more likely to have pathological fractures.

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23
Q

What type of paraproteins do most myeloma patients have?

A

Paraprotein bands with an excess of one light chain

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24
Q

What is the most common type of paraprotein in myeloma?

A

IgG kappa myeloma

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25
Q

What is light chain myeloma?

A

Myeloma plasma cells only secrete paraproteins with light chains and don’t produce heavy chains.

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26
Q

What is non-secretory myeloma?

A

Paraproteins and light chains aren’t detected in the blood; diagnosis is made by bone marrow biopsy.

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27
Q

What does a skeletal survey include?

A

A set of x-rays of multiple skeletal sites including skull, long bones, digits, spine, ribs.

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28
Q

What will a skeletal survey show in myeloma?

A

Lytic lesions, pathological fractures, and pepper pot skull.

29
Q

What do kidney function tests reveal in myeloma?

A

High creatinine and urine protein electrophoresis (UPEP) to detect Bence-Jones proteins.

30
Q

What does a full blood count (FBC) show in myeloma?

A

Anaemia.

31
Q

What is the serum calcium level in myeloma patients?

A

Increased.

32
Q

What is the management for renal failure?

A

IV fluids and dialysis

33
Q

What is the management for hypercalcemia?

A

IV fluids and bisphosphonates

34
Q

What is the management for pain?

A

Analgesia, radiotherapy for bones affected

35
Q

What is the management for fractures?

A

Radiotherapy or surgery

36
Q

What is the management for spinal cord compression?

A

Steroids and radiotherapy

37
Q

What is the management for anaemia?

A

Blood transfusion or EPO transfusion

38
Q

What is the management for infections?

A

Antibiotics

39
Q

What is the management for psychological distress due to insurability?

A

Psychological support

40
Q

What is the chemotherapy protocol for patients over 70 years old?

A

They will receive chemotherapy only

41
Q

What is the chemotherapy protocol for patients younger than 70 years old?

A

They will have chemotherapy followed by high dose chemotherapy and autologous stem cell transplant

42
Q

How are stem cells harvested for transplantation?

A

Stem cells are harvested from patient blood or bone marrow, concentrated, and cryopreserved

43
Q

What is the purpose of high doses of chemotherapy in myeloma treatment?

A

To kill off as much myeloma as possible

44
Q

What is an example of a drug with high efficacy in myeloma treatment?

A

Thalidomide

Thalidomide has been used since 1999 and can be used as monotherapy or with other chemotherapies.

45
Q

What are some side effects of thalidomide?

A

Neuropathy, venous thrombosis, sedation, constipation, phocomelia (birth defects)

46
Q

What are more potent alternatives to thalidomide?

A

Lenalidomide or pomalidomide

These cause less constipation, sedation, and neuropathy but are immunomodulatory and anti-angiogenic.

47
Q

What is daratumumab used for?

A

It targets anti-CD38 antibody expressed by plasma cells

48
Q

What are examples of proteasome inhibitors effective against myeloma?

A

Bortezomib, carfilzomib, and ixazomib

These are often used in combination with steroids.

49
Q

What is Monoclonal Gammopathy of Undetermined Significance (MGUS)?

A

MGUS is characterized by a paraprotein level lower than myeloma (30g/L), usually less than 10g/L, and is an incidental finding.

50
Q

What is the percentage increase of bone marrow plasma cells in MGUS?

A

Bone marrow plasma cells have increased by less than 10%.

51
Q

What are the CRAB criteria in relation to MGUS?

A

There are no CRAB criteria or end organ damage in MGUS.

52
Q

In which age group is MGUS most common?

A

MGUS is rare in young people but common in people over 80 years old.

53
Q

What is the treatment approach for MGUS?

A

The treatment is to watch and wait until CRAB symptoms occur or the patient has an abnormal light chain ratio.

54
Q

What is a Plasmacytoma?

A

Plasmacytoma manifests as a solitary plasmacytoma of bone or solitary extramedullary plasmacytoma in soft tissues.

55
Q

How is a localized plasmacytoma treated?

A

It is treated with high dose radiotherapy if it is truly localized and has no underlying myeloma.

56
Q

What type of paraproteins do low-grade lymphomas produce?

A

Lymphoma cell clones produce IgM paraproteins.

57
Q

What are the clinical features of low-grade lymphoma?

A

Patients will present with clinical features of lymphoma.

58
Q

What additional risk is associated with IgM paraproteins?

A

There is an additional risk of hyperviscosity due to the large pentameric IgM molecule.

59
Q

What is primary amyloidosis?

A

Primary amyloidosis is a protein conformation disorder where clonal plasma cells make light chain fragments deposited in organs as insoluble amyloid protein.

60
Q

What is the prognosis for untreated primary amyloidosis?

A

The prognosis is 12-14 months if untreated.

61
Q

Which organs are most commonly affected by amyloidosis?

A

Amyloidosis can affect any organ but most commonly affects the heart, kidneys, peripheral nerves, liver, gastrointestinal tract, and skin.

62
Q

What are the heart-related complications of amyloidosis?

A

It can cause congestive cardiomyopathy and wall thickening.

63
Q

What kidney condition can result from amyloidosis?

A

It can cause nephrotic syndrome (protein leak) with or without renal failure.

64
Q

What is a common gastrointestinal symptom of amyloidosis?

A

Macroglossia (enlarged tongue) and malabsorption.

65
Q

What is the investigation method for amyloidosis?

A

Tissue biopsy to show affected organs, e.g., renal biopsy shows Congo red stain with characteristic apple-green birefringence.

66
Q

What does a subcutaneous fat aspirate show in amyloidosis?

A

It shows where amyloid usually deposits.

67
Q

How does amyloidosis due to myeloma differ from primary amyloidosis?

A

Amyloidosis due to myeloma will show plasma cell increase by at least 10% in bone marrow.

68
Q

What is the management for amyloidosis?

A

Organ specific supportive treatment and treatment of underlying cause with chemotherapy used for myeloma.

69
Q

What effect does chemotherapy have on amyloidosis?

A

Chemotherapy treats plasma cell clones instead of amyloid itself and will cause gradual regression of amyloid.

Clinical lectures: Yr2 (52 decks)

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