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Haematology > Multiple Myeloma, MGUS and Amyloidosis > Flashcards

Multiple Myeloma, MGUS and Amyloidosis Flashcards

1
Q

What is Multiple Myeloma?

A

a malignant proliferation of plasma cells derived from one clone

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2
Q

What is the epidemiology of MM?

A

median age at diagnosis 70 years
M > F
Blacks: Whites, 2:1
highest incidence in African Americans and Pacific Islanders

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3
Q

What are the common symptoms in MM?

A 
CRAB criteria:
Hypercalcaemia
renal pathology ~50%, renal failure 25%
normocytic normochromic anaemia - 80%
- normal haematinics
Bone pain - affects nearly 70%

Also:
Recurrent infections
hypercalcaemia

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4
Q

What type of bone lesion occurs in MM and what is the pathogenesis behind this?

A

Lytic bone lesions
- best seen on plain radiography
proliferation of tumour cells which activate osteoclasts and suppress osteoblasts

increased osteoclast activity is mediated by osteoclast activating factors (OAFs) which are made by myeloma cells

  • mediated by several cytokines
  • IL-1, VEGF, RANK ligand (receptor activator of NFkB), TNF

osteoblasts are suppressed by dickhoff-1 (yes that is its real name) also produced by myeloma cells

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5
Q

What are the complications of bone lesions?

A

hypercalcaemia
bone pain
pathologic fractures
spinal compression fractures and vertebral collapse

do not get raised ALP as there is not increased osteoblastic activity

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6
Q

Why are patients with MM predisposed to infection?

A

hypogammaglobulinaemia
- decreased production and increased destruction of normal AB
- poor responses against polysaccharide Ags
Slow granulocyte lysozyme concentration
impaired granulocyte migration
May have decreased CD4+ count
abnormalities in complement function

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7
Q

What is the underlying pathology in the renal impairment of MM?

A 
tubular damage with excretion of light chains
Hypercalcaemia
Glomerular amyloid deposits
NSAID use for bone pain
bisphosphonate use
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8
Q

What are the diagnostic criteria for MGUS?

A

serum monoclonal protein

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9
Q

What is the incidence of MGUS?

A

1% at age 50

10% at age 75

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10
Q

What is the rate of progression from MGUS to MM?

A

approx 1% per year

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11
Q

What features predict increased risk of progression from MGUS to MM?

A

Non IgG subtype
abnormal kappa:lambda free light chain ratio
paraprotein (serum M protein) > 15g/L

absence of all 3 features - 5% risk of progression
presence of all 3 features - 60% over 20 years

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12
Q

What are the diagnostic criteria for MM?

A
  • monoclonal protein in serum and/or urine
  • bone marrow clonal plasma cells or biopsy proven plasmacytoma
  • myeloma related end-organ damage (CRAB criteria)
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13
Q

What are the frequencies of the different type of MM?

A

IgG ~60%
IgA ~ 25%
light chain myeloma 20%
IgM/IgD

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14
Q

What is going on if there are no urinary light chains and no paraprotein?

A
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15
Q

What is the staging system for MM?

A

combination of beta 2 micro globulin and albumin forms the basis for the Internation Staging System

Stage 1: albumin > 35g/L and B2M 5.5
- median survival 29 months

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16
Q

What are the most important predictors for survival in MM?

A
  1. serum beta 2 microglobulin is the most powerful predictor of survival - light chain for MHC class 1
    - used in combination with albumin in the ISS
  2. cytogenetics
17
Q

What is the treatment for MGUS/smouldering myeloma?

A

No specific treatment

  • 6 month follow-up if high risk, otherwise annual
  • serum electrophoresis
  • FBC
  • Creat
  • Calcium
18
Q

What is smouldering myeloma?

A

serum monoclonal protein > 30g/L
bone marrow monoclonal plasma cells >10%
no end organ damage (CRAB criteria)

19
Q

What blood tests should be performed for the work-up for MM?

A 
FBC and Blood film -  roluleaux
Creatinine, urea and electrolytes
Liver function tests, calcium, magnesium, phosphate, urate β2 micro globulin *
Albumin*
Lactate dehydrogenase (LDH)
Serum electrophoresis and immunofixation
Serum free light chain analysis
24-hour urine protein and electrophoresis studies
  • prognostic
20
Q

What other tests should be performed to investigate once there is a suspicion of MM?

A 
Skeletal survey
Whole spine MRI
Bone marrow aspirate and trephine
- cytogenetic analysis/FISH for common translocations, immunohistochemistry and flow cytometry
- plasma cells are CD138 +
21
Q

What are the treatment options for MM?

A

If age

22
Q

What drugs are used in combination therapy for the treatment of MM?

A

Steroid + cytotoxic + novel immunomodulatory agent or proteasome inhibitor

cytotoxic: Cylcophosmide / Doxorubicin
novel agents: Thalidomide/Lenolidamide
proteasome inhibitor: bortezomib

These are used in induction and also in treatment for those who are not transplant eligible in different combinations
choice of drugs usually determined by side effect profile

23
Q

What maintenance therapy is given after transplant?

A

Thalidomide (or Lenolidamide if intolerant to Thalidomide) +/- Prednisone

24
Q

How is bone disease managed in MM?

A

Monthly Pamidronate

RT to bony lesions

25
Q

What is Woldenstroms Macroglobulinaemia?

A

Malignancy of plasma cells that secrete IgM
Associated with lymphadenopathy and hepatosplenomegaly and hyper viscosity syndrome
- similar to MM but different treatments

26
Q

What mutation is commonly found in Woldenstroms?

A

MYD88 somatic mutation has been reported in >90% of patients with WM and the majority of patients with IgM MGUS
- used to distinguish from IgM MM (rare), marginal zone lymphoma and CLL

27
Q

What featured distinguish WM from MM?

A

absence of bony lytic lesions
can be associated with a demyelinating peripheral neuropathy
only ~20% secrete light chains so renal impairment is not common
hyperviscosity
- presentations with epistaxis, visual disturbance, headache, transient paresis
hepatosplenemegaly is common
rouleaux and positive coombes test common

28
Q

When is treatment indicated in WM?

A
  • symptoms
  • worsening anaemia
  • hyper viscosity
  • lymphadenopathy or hepatosplenomegaly
29
Q

What is the treatment for WM?

A
  • acute hyper viscosity is managed with plasmapheresis because 80% of IgM paraprotein is intravascular
  • Bortezomib
  • Bendamustine
  • Rituximab
  • Fludarabine
30
Q

What is Bortezomib and what are its side effects?

A

Proteasome inhibitor - degrades intracellular proteins
used in combination with Dexamethasone
- main side effect is painful peripheral neuropathy

31
Q

How does Thalidomide work and what are the main side effects?

A

Multiple actions, precise mechanism unknown

  • anti-angiogenic
  • oxidative stress-inducing effects
  • inhibits TNF-α, IL-6, IL-10 and IL-12 production
  • modulates the production of IFN-γ
  • enhances the production of IL-2, IL-4 and IL-5 by immune cells
  • main side effects: - less severe with Lenolidamide
  • drowsiness
  • constipation
  • VTE
  • peripheral neuropathy
32
Q

What is Amyloidosis?

A

a group of protein folding disorders characterised by extracellular deposition of insoluble polymeric protein fibrils in tissues and organs

  • most common type of systemic amyloidosis
33
Q

What are the classical features of AL Amyloid?

A

extensive mutlosystem involvement from deposition of light chains in tissues in any organ outside the CNS

  • renal involvement 70-80% - usually manifests as proteinuria
  • cardiomyopathy 50-60% - concentrically thickened ventricles and diastolic dysfunction on Echo sparkly appearance”
  • peripheral neuropathy, autonomic dysfunction, GI motility disorders
  • macroglossia
  • functional hyposplenism
  • easy bruising, “racoon eyes”
  • generalise fatigue
34
Q

What is the pathogenesis of AL Amyloid?

A

a clonal expansion of bone marrow plasma cells that secrete a monoclonal immunoglobulin light chain which deposits as amyloid fibrils in tissues

35
Q

In what conditions can AL Amyloidosis occur?

A

Multiple Myeloma
Non-Hoskins Lymphoma
Waldenstroms

36
Q

What diagnostic tests are performed for Amyloid?

A

serum or urinary free light chains
Abdominal fat pad biopsy
- can also biopsy kidney, liver etc but fat pad safer and reasonably high yield
- amyloid stains green under congo red stain
abdominal fat pad + BM biopsy - 90%

37
Q

What is the treatment for AL Amyloidosis?

A

Bortezomib +/- autologous SCT

Haematology (8 decks)

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