Multiple Myeloma Flashcards
what is multiple myeloma?
- a disease of plasma cells, in which one particular plasma cell clone begins to replicate uncontrollably, resulting in massive overproduction of one type of immunoglobulin
- this spike in a specific form of immunoglobulin can be seen as a monoclonal band on serum and urine electrophoresis
how do abnormal plasma cell clones in multiple myeloma affect normal blood cell production?
they accumulate in the bone marrow, which prevents normal blood cell production. this leads to:
- anaemia
- impaired immune function
- low platelets
what are the effects of paraproteins in multiple myeloma?
they can damage the kidneys by forming protein casts in the renal tubules
what are paraproteins?
abnormal immunoglobulin light chains produced by plasma cells
how is osteoclast activity affected in multiple myeloma?
the abnormal plasma cells secrete factors that activate osteoclasts to break down bone, resulting in:
- widespread lytic lesions
- bone pain
- hypercalcaemia
what type of immunoglobulin is most commonly produced in myeloma?
IgG - 2/3
IgA - 1/3
IgD/IgM - rare
what is a mnemonic to remember the most common features of myeloma?
CRAB
hyperCalcaemia
Renal failure
Anaemia
Bone lesions
what are the causes of renal failure in multiple myeloma?
-occurs primarily due to the tubulopathic effects light chains have on renal tubules
- hypercalcaemia results in nephrocalcinosis
- direct invasion of renal tissue by plasma cells
- amyloidosis
- recurrent UTIs secondary to reduced immune function
what are the symptoms of renal failure in multiple myeloma?
- uraemia (e.g. nausea, vomiting, weight loss)
- hyperphosphatemia (e.g. pruritus, muscle cramping)
- pulmonary oedema (e.g. SOB, oedema)
how does multiple myeloma result in immunocompromise?
- the immunoglobulin is mutated, faulty, and ineffective
- production of normal immunoglobulin is impaired
- the most common infections are respiratory and urinary
what are the symptoms of infection in multiple myeloma?
- fevers
- rigors
- productive cough
- dysuria
- rash
- headache
what are the neurological symptoms caused by the complications of myeloma?
- hypercalcaemia (e.g. confusion, weakness, fatigue)
- hyperviscosity (e.g. headache, visual disturbance)
- amyloid deposition (e.g. peripheral neuropathy)
- spinal cord compression (e.g. limb weakness, loss of bladder/bowel control)
what are the investigations for multiple myeloma?
- FBC
- U&Es
- bone profile
- ESR
- blood film
- Ig
- serum + urine protein electrophoresis
- serum free light chains
- MRI
- skeletal survey
- bone marrow biopsy
what does a blood test show in multiple myeloma?
- FBC: anaemia (normocytic + normochromic), neutropaenia, thrombocytopaenia
- U&Es: ↑ creatinine
- bone profile: hypercalcaemia, hyperphosphatemia
- ESR: ↑
- blood film: rouleaux formation
what are the three distinct diagnoses within the myeloma spectrum of disease?
- symptomatic myeloma
- asymptomatic myeloma
- monoclonal gammopathy of undetermined significance
what are the diagnostic criteria for symptomatic myeloma?
- clonal plasma cells >10% on bone marrow biopsy or in a biopsy from other tissues
- a monoclonal protein (paraprotein) in either serum or urine
- evidence of end-organ damage related to the plasma cell disorder
what is asymptomatic myeloma?
- often called smouldering myeloma
- is differentiated from symptomatic myeloma by the absence of end-organ damage
what is the diagnostic criteria for asymptomatic myeloma?
- serum paraprotein >30 g/L
- +/- clonal plasma cells >10% on bone marrow biopsy
- no myeloma-related organ or tissue impairment
what is monoclonal gammopathy of undetermined significance (MGUS)?
- it involves the presence of elevated serum paraproteins but at a lesser level than actual myeloma (<30 g/L)
- the bone marrow has a smaller number of clonal plasma cells within it
- there is no end-organ damage
what is the diagnostic criteria for MGUS?
- serum paraprotein <30 g/L
- clonal plasma cells <10% on bone marrow biopsy
- no myeloma-related organ or tissue impairment
what is the initial therapy for multiple myeloma?
- autologous hematopoietic stem cell transplantation involves extracting a patient’s stem cells, followed by an initial course of induction chemotherapy
- the extracted stem cells are then reintroduced post-chemotherapy
- a small number of patients receive allogeneic stem cell transplantation
how is maintenance achieved in the treatment of myeloma?
this involves regular chemotherapy, which has been shown to increase progression-free survival
how is relapse managed in multiple myeloma?
- the patient may undergo re-treatment with the original agent they previously received
- alternatively, they may be treated with another chemotherapy agent
- some relatively healthy patients may undergo a second autologous stem cell transplant
