Myeloma and Plasma Cell Disorders

Question 1

Explain what a polyclonal increase in immunoglobulins involves and what could cause it?

Answer 1

increase in immunoglobulins produced by many different plasma cells
this is a reactive process and does not indicate an underlying marrow problem

Question 2

4 causes of a polyclonal increase in immunoglobulins?

Answer 2

infection
auto-immune
malignancy (reaction of host to malignant clone)
liver disease

Question 3

Explain what a monoclonal increase in immunoglobulins involves and what could cause it?

Answer 3

all derived from clonal expansion of a single B cell
identical antibody structure and specificity (size and charge)
monoclonal immunoglobulin = paraprotein
marker of underlying clonal B cell or plasma cell disorder

Question 4

What is a monoclonal immunoglobulin also called?

Answer 4

paraprotein

Question 5

Explain the tests that can be used to detect monoclonal and polyclonal immunoglobulins?

Answer 5

serum electrophoresis:

• proteins are separated into distinct bands/ zones depending on size and charge
• Ig should be found in the gamma region
• normally gamma region should be diffuse with no distinct bands because lots of different Ig
• if there is a distinct band in the gamma region this suggests there are monoclonal Ab/ paraprotein

can then do serum immunofixation to classify the abnormal protein band

Question 6

What is myeloma?

Answer 6

malignant disease of bone marrow plasma cells
there is clonal expansion of abnormal, proliferating plasma cells producing a monoclonal paraprotein mainly IgG (55%) or IgA (20%)

Question 7

Who tends to get myeloma?

Answer 7

disease of the elderly- median age at presentation > 60, rare under 40
more common in males
more common in Black Africans but less common in Asians

Question 8

Explain the clinical features of myeloma?

Answer 8

Direct tumour cell effects: 
lytic bone lesions 
hypercalcaemia 
bone pain
replacement of normal marrow causing marrow failure 

paraprotein mediated effects:
renal failure
immunosuppression (due to reduction in normal antibodies)
hyper viscosity (increase in amount of protein in serum)
amyloid

Question 9

Explain what causes lytic bone disease in myeloma?

Answer 9

vicious cycle
malignant plasma cells produce cytokines which interact with osteoblasts and osteoclasts
this causes up regulation of osteoclasts but down regulation of osteoblasts
activated osteoclasts produce other cytokines that in turn encourage myeloma cells to divide and multiply

Question 10

What symptoms does bone lysis in myeloma cause?

Answer 10

causes bone pain, commonly backache due to vertebral involvement
can get pathological fractures
can get spinal cord compression if lesions cause fractures of vertebra

Question 11

What are the symptoms of hypercalcaemia?

Answer 11

bones > pain, osteoporosis and pathological fractures
stones > renal colic from stones, polydipsia, polyuria
abdominal groans > abdo pain, constipation
psychiatric moans > chronic can cause depression but acute hypercalcaemia can cause confusion

Question 12

Why do you get hypercalcaemia in myeloma?

Answer 12

due to the bone destruction

Question 13

Explain what damages the kidney in myeloma?

Answer 13

light chain cast nephropathy > due to low molecular weight, light chains can pass through glomerular filtrate and cause damage to the epithelial cells as the protein precipitates as casts
hypercalcaemia can also cause damage to the kidneys

Question 14

List some investigations for myeloma?

Answer 14

FBC- Hb, WBC and platelet count are normal or low
ESR is often high
U and E- evidence of kidney injury
serum calcium may be raised
serum electrophoresis and immunofixation
skeletal survey showing lytic bone lesions
check urine for Bence Jones protein (light chains)

Question 15

What may be present in the urine in myeloma?

Answer 15

bence jones proteins

Question 16

What is the prognosis for myeloma?

Answer 16

myeloma is incurable and relapses are inevitable

survival is now 5-10 years for younger patients

Question 17

Explain the main treatment for myeloma?

Answer 17

combination chemotherapy is mainstay:

• corticosteroids - dexamethasone
• alkylating agents- cyclophosphamide, melphalan
• novel agents like thalidomide, bortezomib and lenalidomide
• monoclonal antibodies - daratumumab
• high dose chemo/ autologous stem cell transplant in fit patients (take stem cells out before chemo and then put them back in after)

Question 18

Explain symptom control management for myeloma?

Answer 18

treat kidney disease supportively
opiates for pain (avoid NSAIDs as they aren’t good for the kidneys)
local radiotherapy - good for pain relief or spinal cord compression
bisphosphonates - corrects hypercalcaemia and bone pain
vertebroplasty- injection of sterile cement in fractured bone to stabilise

Question 19

What is the definition of monoclonal gammopathy of undetermined significance (MGUS)?

Answer 19

• paraprotein < 30 g/l, bone marrow plasma cells < 10%
• no evidence of myeloma and end organ damage
• should be concerned if young and increased paraprotein (vs older with low level MGUS)

Question 20

What is AL amyloidosis/ primary light chain?

Answer 20

rare disorder
small plasma cell clone like in MGUS
mutation in the light chain results in an altered structure
these altered light chains precipitate in tissues as insoluble beta pleated sheets
accumulation of amyloid in tissues causes organ damage
slowly progressive
multi system disease

Question 21

Explain how AL amyloidosis may cause organ damage in different organs?

Answer 21

kidney- nephrotic syndrome
heart- cardiomyopathy
liver- organomegaly, deranged LFTs
neuropathy- autonomic, peripheral 
GI tract- malabsorption

Question 22

What will amyloid look like on biopsy?

Answer 22

congo red staining causes apple green birenfrigence of stained fibres under polarised light

Question 23

Treatment of AL amyloidosis?

Answer 23

similar to myeloma with chemo to switch off light chain supply