Myeloma

Question 1

Symptoms/signs

Answer 1

Constipation, nausea, poor appetite, confusion (hypercalcaemia)
Thirst (renal failure)
Fatigue + pallor (anaemia
Bleeding/bruising (low platelets)
Back pain (lytic bone lesions, fractures)
Susceptibility to infection

Question 2

What is myeloma?

Answer 2

Malignancy of plasma cells

Question 3

Mechanisms of renal failure in multiple myeloma

Answer 3

Monoclonal production of Igs (antibodies) - malignancy starts from a single cell and this replicates over and over, causing production of only the type of antibody that that cell produces. Theses Ig are proteins - these can precipitate and deposit in kidney, resulting in renal failure.

Question 4

What does the CRAB(BI) acronym stand for?

Answer 4

Calcium (hypercalcaemia)
Renal failure
Anaemia
Bone lesions (back pain)
(Bleeding/bruising
Infection)

Question 5

Investigations for multiple myeloma

Answer 5

FBC, U+Es, calcium
Serum or urine protein electrophoresis - raised concentrations of monoclonal IgA/IgG (Bence Jones proteins in urine)
Bone marrow biopsy
Whole body MRI to survey skeleton

Question 6

Median age at presentation

Answer 6

70

Question 7

Diagnostic criteria

Answer 7

1) Monoclonal plasma cells in the bone marrow >10%
2) Monoclonal protein within the serum or the urine
3) Evidence of end-organ damage e.g. hypercalcaemia, elevated creatinine, anaemia or lytic bone lesions/fractures

Question 8

Mechanism of bone lesions and hypercalcaemia in myeloma

Answer 8

Increased bone turnover - malignant plasma cells release factors that increase osteoclast activity, resulting in lytic bone lesions and make fractures more likely. Also results in hypercalcaemia.

Question 9

Mechanism of anaemia + thrombocytopaenia in myeloma

Answer 9

Crowding of bone marrow - malignancy growing uncontrollable and plasma cells are overcrowding bone marrow, so no longer producing RBCs and platelets

Question 10

Mechanism of susceptibility to infection in myeloma

Answer 10

Decreased production of normal Igs

Question 11

For those who have just been diagnosed with symptomatic multiple myeloma, treatment begins with induction therapy.
What is this?

Answer 11

If suitable for autologous stem cell transplantation = Bortezomib + Dexamethasone

If not = thalidomide + an Alkylating agent + Dexamethasone

Question 12

After completion of treatment, patients are monitored every 3 months with?

Answer 12

Blood tests and electrophoresis

Question 13

1st line treatment for relapse

Answer 13

Bortezomib monotherapy

Question 14

What is autologous stem cell transplant?

Answer 14

Own stem cells removed
Given chemo
Own stem cells replaced

Question 15

Symptoms/complications management

Answer 15

Analgesia 
Zoledronic acid
Annual flu vaccinations
May get Ig replacement therapy
VTE prophylaxis
Consider EPO analogue

Question 16

Structure of immunoglobulins

Answer 16

Four polypeptide subunits, bound with disulphide bones, to form a Y shaped structure
Two heavy chains + two light chains
Constant region and a variable region 
Variable regions contain specific type of sequences that can bind to a specific antigen (antigen binding sites)
Constant regions - determine the class of antibody (e.g. IgG, IgE etc)

Question 17

IgM

Answer 17

Found on B lymphocytes’ membrane
Effective against viral agents
First Igs to be secreted in response to an infection

Question 18

IgG

Answer 18

Most common type

Involved in immunity against pathogens - enhance phagocytosis

Question 19

IgE

Answer 19

Involved in type 1 hypersensitivity reactions

Binds to mast cells/basophils and causes the release of histamines

Question 20

IgA

Answer 20

Primary antibody found in airways and digestive tract

Found in breast milk

Question 21

IgD

Answer 21

The antigen receptor found on B lymphocytes

PLay a role in differentiating B lymphocytes to plasma cells

Question 22

Function of immunoglobulins

Answer 22

When antibody binds to antigen

• -> form antibody-antigen complex
• -> elicits response to kill that pathogen

3 mechanisms:

1) Inactivate pathogen by binding to antigen’s receptors so it the antigen can’t bind onto healthy cells
2) Labels infected cell for destruction by WBCs
3) Agglutination - several ab-antigen complexes form insoluble complex that inactivates the pathogen

Question 23

Define paraproteinaemia

Answer 23

presence of excessive amounts of myeloma protein or monoclonal gamma globulin in the blood

Question 24

What is MGUS?

Answer 24

Monoclonal gammopathy of undetermined significance
aka benign paraproteinaemia

= common condition that causes a paraproteinaemia and is often mistaken for myeloma.

50% develop myeloma within 15 years.

Question 25

How to differentiate MGUS and myeloma?

Answer 25

normal immune function
normal beta-2 microglobulin levels
lower level of paraproteinaemia than myeloma (e.g. < 30g/l IgG, or < 20g/l IgA)
stable level of paraproteinaemia
no clinical features of myeloma