MULTIPLE MYELOMA Flashcards

1
Q

What is multiple myeloma?

A

A heterogenous group of conditions characterised by disordered proliferation of plasma cells and hence associated with the presence of monoclonal immunoglobulins in the serum or urine.

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2
Q

What age group are most often affected by multiple myeloma?

A

Elderly. Very rare before 40, but 3 in 10,000 in over 80s.

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3
Q

What is the pathogenesis of multiple myeloma?

A

Arises in a post-germinal centre B lymphocyte in a lymph node or the spleen. The neoplastic cells then move to the bone marrow where the environment facilitates plasma cell proliferation. This causes bone marrow failure.

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4
Q

How are bones affected in multiple myeloma?

A

Osteoblasts are inhibited as in the secretion of osteoprotogerin (OPG). As a result, osteoclasts are no longer inhibited and there is lytic destruction of the bone.

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5
Q

What is the most common type of monoclonal paraprotein found in multiple myeloma patients?

A

IgG - 60% of patients

IgA - 20-25%

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6
Q

What are the renal complications of multiple myeloma?

A

Renal failure as a result of hyperviscosity of the blood, protein deposition in renal tubules, hypercalcaemia and amyloid.

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7
Q

Which ethnic group are most at risk of developing multiple myeloma?

A

Afro-Caribbean

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8
Q

What are the complications of multiple myeloma?

A
Bone pain
Osteolytic lesions leading to fracture
Anaemia
Bleeding
Hypercalcemia
Acute kidney injury
Infection
Spinal cord compression
Neuropathy
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9
Q

What percentage of all cancers does multiple myeloma make up?

A

1%

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10
Q

Is there a familial link to multiple myeloma?

A

Cases of familial multiple myeloma are extremely rare.

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11
Q

What are the classic symptoms of multiple myeloma?

A
Weight loss
Fatigue
Bone pain
Bleeding
Back ache
Swollen ankles
Infection
Impaired vision
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12
Q

What is the most common presenting complaint which eventually leads to a diagnosis of multiple myeloma?

A

Bone pain

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13
Q

What investigations would you order for someone with suspected multiple myeloma?

A
FBC
ESR
U&Es
GFR
Plasma viscosity
Blood film
Serum electrophoresis - Look for M protein and immunoglobulins
Urine electropheresis
Bone marrow aspirate
X-ray/CT/MRI - skeletal survey
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14
Q

What might the blood tests of someone with multiple myeloma show?

A
Normochromic normocytic anaemia
Neutropenia
Thrombocytopenia
Raised ESR
High calcium
Normal alkaline phosphotase (suppressed osteoblast activity)
High viscosity
Renal dysfunction
Presence of paraprotein
Low albumin (advanced disease)
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15
Q

What might the blood film of someone with multiple myeloma show?

A

Rouleaux formation

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16
Q

What is the most sensitive imaging technique for myeloma?

A

MRI

17
Q

What percentage of multiple myeloma patients develop amyloid? What are the complications?

A

10%
Renal failure
Cardiac failure
Neuropathy

18
Q

How do assess for amyloid deposition?

A

Serum amyloid P scanning

19
Q

What are the important differential diagnoses in someone with suspected multiple myeloma?

A

Monoclonal gammopathy of undetermined significance (MGUS)

Smouldering multiple myeloma

20
Q

How might you differentiate between multiple myeloma or monoclonal gammopathy of undetermined significance?

A

No single differentiating test although serum IgG concentration over 30g/L is more suggestive of multiple myeloma.

21
Q

What is the immunoglobulin light chain protein found in the urine of multiple myeloma patients?

A

Bence Jones protein

22
Q

How does kidney injury lead to anaemia in multiple myeloma patients?

A

Renal failure leads to reduced production of EPO which in turn leads to anaemia.

23
Q

Why is it not enough to test the urine just by doing a simple dipstick for someone with suspected multiple myeloma?

A

Urine dipstick tests for the presence of albumin. The large amount of protein being deposited in the urine in a MM patient is immunoglobulins. To visualise the protein in the urine you can add sulfosalicylic acid to the sample. Alternatively you can just order a urine electrophoresis.

24
Q

What are the two types of acute kidney injury that may occur as a result of multiple myeloma?

A

Light chain cast nephropathy (myeloma kidney)

Light chain amyloidosis

25
Q

Which type of acute kidney injury associated with multiple myeloma (either light chain cast nephropathy or light chain amyloidosis) will produce a positive result on a urine dipstick?

A

Light chain amyloidosis due to loss of albumin

26
Q

Why do you get Rouleaux formations in a multiple myeloma patient?

A

Hyperviscosity of the blood due to immunoglobulins

27
Q

How are the bone lesions caused by multiple myeloma described on a bone survey?

A

Punched out lytic lesions

28
Q

How is beta-2 microglobulin related to prognosis in multiple myeloma patients?

A

Raised beta-2 microglobulin is a poor prognostic sign

29
Q

What are the three criteria for a diagnosis of multiple myeloma?

A
M protein in the serum or urine
10% or greater clonal plasma bone marrow cells
Organ impairment: CRAB
  Calcium level
  Renal insufficiency
  Anaemia
  Bone lytic lesions
30
Q

What criteria differentiate multiple myeloma from monoclonal gammopathy of undetermined significance (MGUS)?

A

In MGUS:

Serum monoclonal IgG, IgA or IgM is less than 3 g/dL
Clonal bone marrow plasma cells are less than 10%
No organ impairment damage (CRAB)

31
Q

What criteria differentiate multiple myeloma from smouldering multiple myeloma?

A

No organ impairment (CRAB)

32
Q

What are the initial chemotherapy options for multiple myeloma?

A

Lenilidamide
Valcade

Melphalan and prednisolone
Dexamethasone

Infusion chemo: Vincristine, adriamycin plus methylprednisolone or dexamethasone

Investigational therapy: bortezomib, adriamycin and dexamethasone

33
Q

What reduction in paraprotein do most multiple myeloma patients achieve with melphalan?

A

More than 50%

34
Q

What drugs may be used to prolong the plateau phase of multiple myeloma?

A

Interferon-alpha

Thalidomide

35
Q

In addition to the chemotherapy and steroids, what drug might you want to give a multiple myeloma patient experiencing bone lytic lesions?

A

Bisphoshonates