0416 - Plasma Cell Disorders Flashcards
What is M protein in the context of plasma cell disorders?
A monoclonal antibody (gammopathy) which is secreted by neoplastic plasma cells, as in multiple myeloma. IgG is the most common M protein.
What is the pathophysiology of multiple myeloma?
An initial genomic change (often deletion of 13, or translocations at 14q32) leads to a monoclonal antibody of unknown significance.
When this is coupled with microenvironvironment changes in bone marrow (increased bone resorption and angiogenesis), and further genomic changes (N-RAS, K-RAS, p16 methylation), myeloma develops.
What are the key clinical features of myeloma?
M-protein (may be incidental)
CRAB end-organ damage - Hypercalcaemia, renal dysfunction, anaemia, bone disease
Bone marrow suppressions
Recurrent infections.
What key investigations would you perform on a patient suspected of myeloma? What results?
Serum M-protein, either by electrophoresis or serum Ig’s or FLCs - May have high Gamma or other protein or FLC - show elevated Kappa or Lambda B
lood Smear - Rouleaux and peripheral plasma cells
Bone Marrow Biopsy - Enlarged and excessive plasmablasts.
Serum/Urine protein would be elevated.
FBC, UEC - High lymphocytes, otherwise may have pancytopenia, poor
UEC (high calcium, low GFR)
Skull Xray - Osteolytic lesions.
What key investigations would you perform on a known Myeloma?
Bloods - FBC, UEC, Corr Cal (osteoclastic activity, kidney damage, bone marrow suppression)
Beta2 Microglobulin - for prognosis
How can myeloma be distinguished from MGUS (Monoclonal Gammopathy of Unknown Significance)?
Serum or Urine M-protein - Myeloma = >20g/L, MGUS =<30gL (generally <10)
Bone Marrow Plasma cells - Myeloma = high, MGUS = <10%
End organ damage - Myeloma = Present, MGUS absent
Evidence of Lymphoma - Myeloma = may be present, MGUS = absent.
What are the broad treatment stages and principles of a patient with myeloma?
Induction - Control disease, reduce plasma cell burden, reverse complications - possible autologous stem cell transplant.
Consolidation - Ensure durability of response.
Maintenance - Prolong or maintain response, reducing risk of relapse.
Why is thalidomide a valuable immunomodulatory drug for myeloma?
Thalidomide has anti-angiogenic properties, preventing angiogenesis around the lesion.
It also inhibits IgM antibodies (decreasing protein load), increases T4 cells, and inhibits TNF-a and IL6, reducing myeloma growth and altering its interactions with stromal cells.
Why is Bortezomib a valuable proteasome inhibitor in myeloma?
Bortezomib is a proteasome inhibitor which is more effective in cancer cells than healthy cells.
It acts directly on the myeloma, inhibiting proteasome function, as well as inhibiting TNF-a, IL6, and NFKB. It also alters the interaction between stromal and plasma cells.
