HAEMATOLOGY - MYELOMA

Question 1

What is myeloma?

Answer 1

A cancer of plasma cells in the bone marrow
These plasma cells produce non-functional monoclonal paraprotein instead of immunoglobulins = overproduction of M protein

Question 2

How common is multiple myeloma?

Answer 2

The second most common haematological cancer

Question 3

What age does multiple myeloma usually affect?

Answer 3

Older people - about 70

Question 4

What are the symptoms of multiple myeloma?

Answer 4

Bone pain; most commonly back pain
Recurrent infection
Anaemia symptoms
Renal failure symptoms
Symptoms of hypercalcaemia
Rarely, symptoms of hyperviscocity and bleeding due to thrombocytopenia

Question 5

What causes the anaemia, neutropenia and thrombocytopenia seen in myeloma?

Answer 5

Bone marrow infiltration with plasma cells
Kidney failure also causes decreased EPO, decreasing RBC production

Question 6

What causes recurrent infections in those with myeloma?

Answer 6

Paraprotein secretion means there’s a reduction in normal immunoglobulin levels

Question 7

What causes renal impairment in myeloma?

Answer 7

Free light chain (paraprotein) secretion leads to deposition in renal tubules causing cast nephropathy
The hypercalcaemia, NSAID use can also contribute

Question 8

What causes bone pain in myeloma?

Answer 8

Myeloma cells adhere to bone marrow stromal cells. Myeloma cells secrete IL-3 which inhibits osteoblast progenitor cell maturation, decreasing osteoblast activity. The cells also secrete DKK1 which inhibits OPG production by osteoblasts causing an increase in osteclastic activity. Myeloma cells also increase osteoclastic activity through MIP1 alpha and RANKL.
Increased osteoclastic activity without osteoblastic increase causes lytic lesions, usually seen in the spine, skull, long bones and ribs

Question 9

What are the main antibodies associated with myeloma?

Answer 9

IgG and IgA

Question 10

Why does myeloma cause hypercalcaemia?

Answer 10

Bone resorption

Question 11

What symptoms can hypercalcaemia cause?

Answer 11

Nerve problems and dehydration

Question 12

Whats it called when light chains are found in the urine of those with myeloma?

Answer 12

Bence jones proteins

Question 13

How do you investigate myeloma?

Answer 13

Blood tests - anaemia, WCC, Plt, ESR high, increased paraprotein
Blood film - rouleaux formation because of paraprotein
U&Es for kidney function (increased urea, nitrogen and creatinine)
Serum calcium usually raised
Urine tests - bence jones proteins
Bone aspiration
Bone marrow biopsy - >10% plasma cell infiltrate
CT scan - lytic lesions
Free light chain ration >100

(>10% monoclonal plasma cell infiltrate with at least 1 of the four CRAB features; hyperCalcaemia, Renal impairment, Anaemia, Bone involvement)

Question 14

How is myeloma treated?

Answer 14

Transfusions and EPO for anaemia
Hydration, bisphosphonates and high dose steroids for hypercalcaemia and kidney injury
Antibiotics for infections
Radiotherapy and systemic chemotherapy or high dose dexamethasone for bone pain Bisphosphanates can be given too
Preventing pathological fractures by pinning lytic lesions
Stem cell transplants

Question 15

What proportion of cases of MGUS progress to multiple myeloma?

Answer 15

25%

Question 16

What are the 3 types of multiple myeloma?

Answer 16

Smouldering MM - asymptomatic
Symptomatic MM
Non-secretory MM

Question 17

What is the rouleaux formation in myeloma?

Answer 17

The stacking of 4 or more RBCs (RBCs coated with immunoglobulins which makes them sticky so they form chains)

Question 18

What can cause rouleaux formation?

Answer 18

infections
multiple myeloma
Waldenström’s macroglobulinemia
inflammatory and connective tissue disorders
cancers
diabetes mellitus

Question 19

What is electrophoresis?

Answer 19

Electrophoresis is a laboratory technique used to separate DNA, RNA or protein molecules based on their size and electrical charge. It can measure antibodies in blood

Question 20

Whats associated with a poorer prognosis in myeloma?

Answer 20

Worse stage
Older age
High beta-2 microglobulin on blood results
Low level of albumin on bloods
High lactate dehydrogenase on bloods
High creatinine on bloods
Chromosome 13 deletion, 17p deletion, chromosome 14 translocation, extra copy of chromosome 1
Poor kidney function

Question 21

How is myeloma staged?

Answer 21

International staging system - based on beta 2 microglovuli and albumin levels

Question 22

Whats the median prognosis of myeloma?

Answer 22

4-5 years

Question 23

Which patients with myeloma do we treat?

Answer 23

Only those symptomatic or very progressive disease