Myeloma & Plasma Cell Dyscrasias

Question 1

Immunoglobulins contain 2 heavy & 2 light chains. What chain determines the type of antibody produced e.g. IgM or IgG

Answer 1

Heavy chain

Question 2

Where do antigens bind on an antibody

Answer 2

The variable region (heavy & light chains)

Question 3

List the 5 immunoglobulins and state whether they are monomers, dimers or pentamers

Answer 3

IgG, IgD, IgE - monomer
IgA - dimer
IgM - pentamer

Question 4

Describe the basic structure of an immunoglobulin

Answer 4

Constant region
Variable region - 2x light & 2 x heavy chain (antigen binding site)

Question 5

What process creates the variable (antigen binding site) of an immunoglobulin

Answer 5

VDJ region recombination

Question 6

B cell receptor vs antibody

Answer 6

Ig on B cell surface - B cell receptor
Ig free in plasma - antibody

Question 7

Briefly describe the process of plasma cell formation

Question 8

Monoclonal vs polyclonal rise in immunoglobulins cause

Answer 8

Monoclonal - underlying clonal B cell or plasma cell disorder
Polyclonal - reactive change

Question 9

What technique is used to detect immunoglobulins in the plasma

Answer 9

To test for presence of faulty Ig - Serum electrophoresis
To classify the faulty Ig (e.g. IgG) - Serum immune fixation
To quantify the amount of faulty Ig -

Question 10

What is the name for a monoclonal immunoglobulin

Answer 10

Paraprotein

Question 11

What are the 3 main causes of paraproteinaemia

Answer 11

MGUS
Myeloma
Amyloidosis

Question 12

What is MGUS and what characterises it

Answer 12

Monoclonal gammopathy of undetermined significance
- monoclonal paraprotein in the serum or urine
- Paraprotein <30 g/l, bone marrow plasma cells <10%,
- No evidence of myeloma end organ damage

Question 13

Why is MGUS clinically relevant

Answer 13

Is premalignant but increased risk of myeloma

Question 14

What is myeloma

Answer 14

Cancer of a specific type of plasma cell
where there is agenetic mutation
causing it to rapidly and uncontrollably multiply
These plasma cells produce one type ofantibody
§(monoclonal paraprotein)

Question 15

Summarise the effects of myeloma on the body

Answer 15

Bone disease
Bone marrow infiltration
Paraprotein secretion & amyloidosis
Myeloma renal disease

Question 16

Describe the effects of myeloma on bone

Answer 16

Increased osteoclastic without increased osteoblastic activity
=> Lytic lesions
=> Fractures of long bone, vertebral collapse, hypercalcaemia

Question 17

Describe the effects of paraprotein secretion

Answer 17

• Hyper-viscosity => confusion, headaches etc
• Reduced number of normal Ig => recurrent infections
• AL amyloidosis
• Renal failure

Question 18

Describe the effects of myeloma renal disease

Answer 18

Deposition of light chains in tubules leads to cast nephropathy & renal impairment.

Renal impairment can be made worse by:
- Hypercalcaemia & dehydration (associated with myeloma)
- Use of NSAIDs

Question 19

Summarise the clinical presentation of myeloma (think about the effects on the bone, bone marrow, kidneys)

Answer 19

General - weight loss, fatigue, weakness, lytic lesions
Bone - fractures, pain, vertebral collapse
Hypercalcaemia - Bones, stones, groans, moans, dehydration
Bone marrow infiltration - anaemia, infections, bleeding
Cast nephropathy - renal impairment
Paraprotein secretion - hyperviscosity S&Ss (rare)

Question 20

Summarise the initial investigations for patients presenting with S&S of myeloma

Answer 20

• Bloods: FBC, U+Es, creatinine, calcium, CRP, PV
• Serumprotein electrophoresis: for type of paraprotein
• Plain x-ray: of symptomatic areas

Question 21

How would you diagnose myeloma

Answer 21

• Bone marrow aspirate and trephine biopsy: with plasma cell phenotyping
• Immunofixation: of serum and urine to confirm and show the subtype of the paraprotein

Question 22

How would you treat a patient with myeloma kidney disease

Answer 22

• Rehydration
• Stop nephrotoxic drugs
• Damage may be reversible
• Dialysis may be required
• Switch of light chain production (steroids/chemo)

Question 23

How would you treat a patient with myeloma presenting acutely with bone disease & hypercalcaemia

Answer 23

• Hypercalcaemia - fluid and bisphosphonates
• Spinal cord compression - radiotherapy emergency

Question 24

How would you treat a patient with hyper viscosity due to myeloma & paraproteinaemia

Answer 24

Plasmapheresis

Question 25

Summarise the long term management of myeloma

Answer 25

First line
- Combination novel agent chemotherapy
- e.g. ‘novel agent’ with alkylating agent with steroids

If young & minimal comorbidities
- High does chemo &
- autologous stem cell transplant

Symptom control
- opiate analgesia or local radiotherapy (not NSAIDs) for pain
- bisphosphonates for hypercalcaemia & bone pain
- vertebroplasty to stabilise fractured bone

Question 26

What analgesia would you want to avoid in myeloma

Answer 26

NSAIDs

Question 27

What is waldenstroms macroglobulinaemia aka

Answer 27

Lymphoplasmacytoid neoplasm

• it is a clonal disorder of cells intermediate between a lymphocyte & plasma cell

Question 28

Waldenstroms macroglobulinaemia shows clinical features of what two conditions

Answer 28

Lymphoma & myeloma

Question 29

What paraprotein is characteristic of waldenstroms macroglobulinaemia

Answer 29

IgM

Question 30

Clinical presentation of waldenstroms macroglobulinaemia

Answer 30

Tumour effects
- lymphadenopathy
- splenomegaly
- marrow failure

Paraprotein effects
- hyperviscosity (fatigue, confusion, coma, bleeding, cardiac)
- neuropathy (IgM binds to myelin-associated glycoprotein)

B symptoms
- fever
- night sweats
- weight loss

Question 31

Waldenstroms macroglobulinaemia investigations

Answer 31

General
- Blood FBC & PV (marrow failure, hyperviscosity)
- CT imaging (lymphadenopathy, splenomegaly)

Macroglobulinaemia
- Serum protein electrophoresis &
- immunofixation (confirm IgM)
- densitometry (confirm mass)

Diagnosis
- Bone marrow biopsy (lymphoplasmacytes infiltration)

Question 32

Waldenstroms macroglobulinaemia treatment

Answer 32

• Chemotherapy
• Plasmapheresis (removes paraprotein from the circulation)