3.3 Plasma cell disorders

Question 1

What is characteristic of plasma cell disorders?

Answer 1

Proliferation of a single clone of plasma cells resulting in production of M protein (paraprotein)

Question 2

What are the two factor that cause plasma cell neoplasms?

Answer 2

Genetic changes within the plasma cell clone

Changes within the microenvironment facilitating growth

Question 3

What are the common genetic changes for plasma cell disorders?

Answer 3

Translocation of chromosome 14 and deletion of chromosome 13

Question 4

What are the microenvironment changes that occur?

Answer 4

Vasculature, angiogenesis, cell mediated immunity and up regulation of cytokines

Question 5

What are the clinical features of plasma cell disorders?

Answer 5

Incidental finding of M protein 
End organ damage (CRAB) 
- Hypercalcemia  
- Renal dysfunction 
- Anaemia 
- Bone disease 
Bone marrow suppression 
Recurrent infections 
Myeloma

Question 6

What are the flow cytometry features of plasma cell disorders?

Answer 6

MONOCLONAL

CD45-, CD38/138+, CD19- variable expression of CD56

Question 7

What is the process for diagnosis of plasma disorders?

Answer 7

Bone marrow (flow cytometry) 
Skeletal survey (look for lethic lesions) 
Serum/protein studies 
Blood film 
Bone marrow

Question 8

What will you see on blood film for plasma cell disorders

Answer 8

large amount of paraprotein (M protein) which causes the red cells to stack up on oneanother, may also see some plasma cells

Question 9

What will you see in the bone marrow in plasma cell disorders?

Answer 9

Eccentric nucleus, clearing next to the nucleus, larger than they should be, some with central nucleoli which indicates plasma blasts (immature cells)

Question 10

What is the M-protein (paraprotein?)

Answer 10

Monoclonal Ig secreted by an abnormal expanded clone of malignant plasma cells which can be present as whole or free light chains - usually IgG

Question 11

What are the tests to detect M-protein?

Answer 11

Serum electrophoresis then monoclonal antibody fixation

Question 12

What will you see in myeloma?

Answer 12

M protein in serum/urine
Bone Marrow plasma cells
Evidence of end organ damage

Question 13

What will you see in MGUS?

Answer 13

M protein in serum

Question 14

What does the prognosis of M protein depend on?

Answer 14

Type of paraprotein
Levels
Free light chain products

Question 15

What is the treatment of myeloma in transplant eligible patients?

Answer 15

Steroids + new agents
- Thalidomide 
- Lenalidomide  
- Proteosome inhibitors (bortezomib) 
Alkylators 
(chemo rarely used)

Question 16

How to alkylating agents, corticosteroids and bortezomib work in myeloma?

Answer 16

act on the plasma cell clone and inhibit its action

Question 17

How does thalidomide work in myeloma?

Answer 17

Effects the interaction between plasma cells and stromal cells preventing the release of cytokines (TNF and IL6) from stromal cells which would normally stimulate plasma cells. Also facilitates T cell immunity

Question 18

How does bone disease occur in myeloma patients?

Answer 18

Plasma cell clone releases macrophage inhibitory protein which causes changes in the osteoblast receptors. This leads to up regulation of receptor activation of NF-kB ligand (RANKL). This will lead to osteoclast activation leading to resorption of bone

Question 19

What can you use in bone disease in myeloma patients?

Answer 19

Bisphosphanates which inhibit osteoclast function

Question 20

What are the principles of treatment for myeloma?

Answer 20

Induction therapy: reduce plasma cell burden

Consolidation:

Maintenance: thalidomide and lenalidomide