Myeloma Flashcards
Symptoms/signs
Constipation, nausea, poor appetite, confusion (hypercalcaemia)
Thirst (renal failure)
Fatigue + pallor (anaemia
Bleeding/bruising (low platelets)
Back pain (lytic bone lesions, fractures)
Susceptibility to infection
What is myeloma?
Malignancy of plasma cells
Mechanisms of renal failure in multiple myeloma
Monoclonal production of Igs (antibodies) - malignancy starts from a single cell and this replicates over and over, causing production of only the type of antibody that that cell produces. Theses Ig are proteins - these can precipitate and deposit in kidney, resulting in renal failure.
What does the CRAB(BI) acronym stand for?
Calcium (hypercalcaemia) Renal failure Anaemia Bone lesions (back pain) (Bleeding/bruising Infection)
Investigations for multiple myeloma
FBC, U+Es, calcium
Serum or urine protein electrophoresis - raised concentrations of monoclonal IgA/IgG (Bence Jones proteins in urine)
Bone marrow biopsy
Whole body MRI to survey skeleton
Median age at presentation
70
Diagnostic criteria
1) Monoclonal plasma cells in the bone marrow >10%
2) Monoclonal protein within the serum or the urine
3) Evidence of end-organ damage e.g. hypercalcaemia, elevated creatinine, anaemia or lytic bone lesions/fractures
Mechanism of bone lesions and hypercalcaemia in myeloma
Increased bone turnover - malignant plasma cells release factors that increase osteoclast activity, resulting in lytic bone lesions and make fractures more likely. Also results in hypercalcaemia.
Mechanism of anaemia + thrombocytopaenia in myeloma
Crowding of bone marrow - malignancy growing uncontrollable and plasma cells are overcrowding bone marrow, so no longer producing RBCs and platelets
Mechanism of susceptibility to infection in myeloma
Decreased production of normal Igs
For those who have just been diagnosed with symptomatic multiple myeloma, treatment begins with induction therapy.
What is this?
If suitable for autologous stem cell transplantation = Bortezomib + Dexamethasone
If not = thalidomide + an Alkylating agent + Dexamethasone
After completion of treatment, patients are monitored every 3 months with?
Blood tests and electrophoresis
1st line treatment for relapse
Bortezomib monotherapy
What is autologous stem cell transplant?
Own stem cells removed
Given chemo
Own stem cells replaced
Symptoms/complications management
Analgesia Zoledronic acid Annual flu vaccinations May get Ig replacement therapy VTE prophylaxis Consider EPO analogue
Structure of immunoglobulins
Four polypeptide subunits, bound with disulphide bones, to form a Y shaped structure Two heavy chains + two light chains Constant region and a variable region Variable regions contain specific type of sequences that can bind to a specific antigen (antigen binding sites) Constant regions - determine the class of antibody (e.g. IgG, IgE etc)
IgM
Found on B lymphocytes’ membrane
Effective against viral agents
First Igs to be secreted in response to an infection
IgG
Most common type
Involved in immunity against pathogens - enhance phagocytosis
IgE
Involved in type 1 hypersensitivity reactions
Binds to mast cells/basophils and causes the release of histamines
IgA
Primary antibody found in airways and digestive tract
Found in breast milk
IgD
The antigen receptor found on B lymphocytes
PLay a role in differentiating B lymphocytes to plasma cells
Function of immunoglobulins
When antibody binds to antigen
- -> form antibody-antigen complex
- -> elicits response to kill that pathogen
3 mechanisms:
1) Inactivate pathogen by binding to antigen’s receptors so it the antigen can’t bind onto healthy cells
2) Labels infected cell for destruction by WBCs
3) Agglutination - several ab-antigen complexes form insoluble complex that inactivates the pathogen
Define paraproteinaemia
presence of excessive amounts of myeloma protein or monoclonal gamma globulin in the blood
What is MGUS?
Monoclonal gammopathy of undetermined significance
aka benign paraproteinaemia
= common condition that causes a paraproteinaemia and is often mistaken for myeloma.
50% develop myeloma within 15 years.
How to differentiate MGUS and myeloma?
normal immune function normal beta-2 microglobulin levels lower level of paraproteinaemia than myeloma (e.g. < 30g/l IgG, or < 20g/l IgA) stable level of paraproteinaemia no clinical features of myeloma
