Flashcards in Multiple Myeloma Deck (46):
The first 11 cards will be from the "I'd like you to know" slide.
What is an M spike?
Large spike on serum electrophoresis that indicates the presence of monoclonal proteins.
What does immunofixation electrophoresis (IFE) tell you?
IFE follows SPEP. IFE will tell you what type of Ig the monoclonal Ab is.
Name the four components of CRAB.
R- Renal insufficiency
B- Bone destruction
Describe the mechanism of bone destruction in myeloma.
Myeloma cells produce DKK1 leading to increase in RANKL and IL-6 by osteoblast progenitor cells and marrow stromal cells. Osteoblast differentiation is blocked and osteoclast maturation is stimulated.
Stage a myeloma with Durie Salmon.
Stage I- Hb>10, Ca normal or 12, multiple lytic lesions, high M protein w/ IgG>7 or IgA>5, Bence Jones>12g/24hr
Stage a myeloma with ISS.
Stage I- B2m3.5
Stage II- B2m5.5
Name the worst prognostic chromosome abnormality in myeloma.
What 2 classifications of new drugs have changed the way we treat myeloma? MOA?
1. Immunomodulatory Drugs: Thalidomide/Lenalidomide MOA=act via cytokine effects (I think)
2. Proteosome Inhibitors: Bortezomib MOA=inhibits 26S proteasome disrupting cellular homeostasis and causing cell death
When is an autologous transplant indicated in myeloma?
Patients <70 yo and in otherwise good health
Why do Waldenstrom pt's become hyperviscous more commonly than myeloma pt's?
IgM is a much bigger molecule
Name 3 causes of amyloidosis.
Deposition of the 3 following amyloid proteins:
1. Light Chain (secondary to myeloma)
2. Transthyretin (familial)
3. AA (derived from serum amyloid A; osteomyelitis)
That's the end of "I'd like you to know" slides.
It's been real.
Define multiple myeloma.
A malignancy of late B cells that mature principally into neoplastic plasma cells that generally produce a complete and/or partial (light chain) monoclonal immunoglobulin protein.
Blood smear of myeloma shows what?
Roleaux of red cells
SPEP and IFE show what in myeloma?
IFE: type of monoclonal Ig being produced
What 3 things are required for the dx of myeloma?
1. M-protein in serum or urine
2. Marrow clonal plasma cells or plasmacytoma
3. Related organ or tissue impairment
What are the 7 complications of myeloma (includes CRAB)?
1. Bone destruction
3. Renal insufficiency
Bone destruction is manifested how clinically?
Pain. Fractures. Spinal cord compression.
Hypercalcemia is manifested how clinically?
Altered mental status. Renal insufficiency.
What can cause the renal insufficiency seen in myeloma?
Light chain nephropathy, amyloid, uric acid, hypercalcemia, infection.
Common in elderly. M protein present but other multiple myeloma features absent. Other Ig's normal. Less likely to have Bence Jones proteinuria. Rate of progression to monoclonal B cell malignancy is 1% per year.
Describe smoldering myeloma.
In between form of multiple myeloma. Asymptomatic. Serum M protein > 3g/dL OR BM plasma cells >10%. No CRAB.
Is treatment recommended for MGUS and smoldering myeloma?
No. Both diseases are mostly asymptomatic so it is best just to observe and monitor.
What are the clincial presentations/lab findings in myeloma?
Bone pain. Fatigue. Anemia. Renal insufficiency. Hypercalcemia. M-spike on SPEP. M-peak on IFE of serum or urine. Marrow plasma cells >10%. Urine M-protein.
What is the mechanism of lytic lesions in myeloma?
Myeloma cells produce DKK1 leading to increase in RANKL and IL-6 by osteoblast progenitor cells and marrow stromal cells- stimulates osteoclasts, inhibits osteoblasts.
What tests should be run on a patient suspected of having multiple myeloma?
1. CBC w/ differential.
2. Chemistry profile--Calcium levels
4. SPEP (24h), IFE, and quantitative Ig's.
5. Serum free light chain.
6. Skeletal survey. (MRI and PET/CT)
7. Unilateral BM bx --> cytogenetics and FISH
What are the high risk prognostic indicators for multiple myeloma?
-deletion of chr. 13
What are the standard risk prognostic indicators for multiple myeloma?
What are the poor risk prognostic indicators for multiple myeloma?
-B2m >4 (most significant)
-less than CR w/ transplant
-5+ focal lesions
What are the 8 treatment options for multiple myeloma?
1. Alkylating agents i.e. cyclophosphamide, etc.
3. Anthracyclines i.e. doxorubicin, etc.
5. Immunomodulators (thalidomide, lenalidomide)
6. Protesome inhibitors (Bortezomib)
7. Auto- or AlloSCT
8. Biphosphonates: to treat bone disease
Define Waldenstrom's Macroglobulinemia.
Low grade lymphoma which produces excess monoclonal IgM paraprotein.
What are the clinical features of Waldenstrom's?
Almost always >40 yo. Fatigue. Weight loss. Abnormal bleeding. Lymphadenopathy and hepatosplenomegaly. Hyperviscosity syndrome. Monoclonal IgM.
What qualifies hyperviscosity syndrome?
Serum viscosity >4.
What is the clinical presentation of hyperviscosity syndrome?
Headache, blurred vision, mental status change, ataxia.
What are the 8 diagnostic approaches to confirming Waldenstrom's?
3. 24 hour urine collection for protein electrophoresis
4. Serum B2m
5. BM bx
6. Cytogenetic studies (optional)
7. CT of abdomen and pelvis
8. Blood or serum viscosity
Is Waldenstrom's curable?
No, it is only controlled.
What are the 8 therapies for Waldenstrom's?
1. Alkylating agent
3. Purine analogues (fludarabine)
8. Plasmapheresis when serum viscosity >4
Describe Light Chain Amyloidosis.
May be primary disorder or secondary to myeloma. Involves nervous system, heart, GI tract, and liver.
Describe Transthyretin Amyloidosis.
Familial. Same systemic involvement as LC amyloidosis.
Describe AA Amyloidosis.
Due to chronic inflammatory disorders. Renal disease, hepatic, and GI involvement.
How do you diagnose amyloidosis?
Bx to evaluate for light chains and myeloma or chronic inflammatory state.
What is the treatment for LC amyloidosis?
What is the treatment for transthyretin amyloidosis?
What is the treatment for AA amyloidosis?
Treat the underlying chronic disease.