Flashcards in 3.3 Plasma cell disorders Deck (20):
What is characteristic of plasma cell disorders?
Proliferation of a single clone of plasma cells resulting in production of M protein (paraprotein)
What are the two factor that cause plasma cell neoplasms?
Genetic changes within the plasma cell clone
Changes within the microenvironment facilitating growth
What are the common genetic changes for plasma cell disorders?
Translocation of chromosome 14 and deletion of chromosome 13
What are the microenvironment changes that occur?
Vasculature, angiogenesis, cell mediated immunity and up regulation of cytokines
What are the clinical features of plasma cell disorders?
Incidental finding of M protein
End organ damage (CRAB)
- Renal dysfunction
- Bone disease
Bone marrow suppression
What are the flow cytometry features of plasma cell disorders?
CD45-, CD38/138+, CD19- variable expression of CD56
What is the process for diagnosis of plasma disorders?
Bone marrow (flow cytometry)
Skeletal survey (look for lethic lesions)
What will you see on blood film for plasma cell disorders
large amount of paraprotein (M protein) which causes the red cells to stack up on oneanother, may also see some plasma cells
What will you see in the bone marrow in plasma cell disorders?
Eccentric nucleus, clearing next to the nucleus, larger than they should be, some with central nucleoli which indicates plasma blasts (immature cells)
What is the M-protein (paraprotein?)
Monoclonal Ig secreted by an abnormal expanded clone of malignant plasma cells which can be present as whole or free light chains - usually IgG
What are the tests to detect M-protein?
Serum electrophoresis then monoclonal antibody fixation
What will you see in myeloma?
M protein in serum/urine
Bone Marrow plasma cells
Evidence of end organ damage
What will you see in MGUS?
M protein in serum
What does the prognosis of M protein depend on?
Type of paraprotein
Free light chain products
What is the treatment of myeloma in transplant eligible patients?
Steroids + new agents
- Proteosome inhibitors (bortezomib)
(chemo rarely used)
How to alkylating agents, corticosteroids and bortezomib work in myeloma?
act on the plasma cell clone and inhibit its action
How does thalidomide work in myeloma?
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
How does bone disease occur in myeloma patients?
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
What can you use in bone disease in myeloma patients?
Bisphosphanates which inhibit osteoclast function