Multiple Myeloma Flashcards
What is a paraprotein?
Monoclonal antibody that arises from a clone of lymphocytes or plasma
Paraproteins occur when plasma cells make the same antibody in response to a trigger, causing a monoclonal increase in globulins.
How do normal plasma cells behave compared to paraprotein-producing plasma cells?
Normal plasma cells make different antibodies, causing a polyclonal increase in globulins.
What is the main investigation for paraproteins?
Serum protein electrophoresis
This involves applying a plasma drop to a gel strip with an electric current to separate proteins with different charges.
What does an additional band on the serum protein electrophoresis graph indicate?
The monoclonal ‘M’ component
This band is abnormal and not present in a normal individual.
What is the purpose of the immunoassay in paraprotein investigation?
Detects free light chains in serum
It uses an antibody against the surface of the light chain that binds to the heavy chain, so bound light chains aren’t measured.
What does the ratio of serum lambda to kappa light chains indicate?
Paraproteinaemia
Paraproteins only make one type of light chain, leading to an excess of one type.
What does a positive result for Bence-Jones protein in urine indicate?
Multiple myeloma or malignant lymphomas
It is also used to detect primary amyloidosis.
What is multiple myeloma?
Malignant cancer due to overproliferation of plasma cells in the bone marrow.
What is the median diagnostic age for multiple myeloma?
60-65 years old.
Is multiple myeloma common in children?
No, it does not occur in children.
What are the hallmark symptoms in the CRAB criteria for end-organ damage in multiple myeloma?
The 4 hallmark symptoms are:
* Hypercalcaemia
* Renal failure
* Anaemia
* Bone lesions.
What causes hypercalcaemia in multiple myeloma?
Bone remodelling.
What causes renal failure in multiple myeloma?
Tubular damage from light chain deposition and other factors like NSAIDs and hypercalcaemia.
What causes anaemia in multiple myeloma?
Bone marrow replacement and renal damage decreasing EPO synthesis.
What causes bone lesions in multiple myeloma?
Activation of osteoclasts and inhibition of osteoblasts due to OPG and RANKL production.
What additional complications do patients with multiple myeloma face?
Increased risk of infections and spinal cord compression due to plasmacytomas.
What is a common presentation symptom for patients with multiple myeloma?
Back pain, height loss, kyphosis due to vertebral body collapse.
What investigation shows an increase in plasma cells in multiple myeloma?
Bone marrow aspirate.
What will a bone marrow aspirate or trephine show in myeloma?
Increase in bone marrow plasma cells by at least 10%
What imaging techniques can show lytic lesions in myeloma?
X-ray, CT, MRI, PET scans
Where are lytic lesions most commonly found in myeloma?
In long bones and skull
Why should patients with myeloma be assessed urgently?
They are more likely to have pathological fractures.
What type of paraproteins do most myeloma patients have?
Paraprotein bands with an excess of one light chain
What is the most common type of paraprotein in myeloma?
IgG kappa myeloma
What is light chain myeloma?
Myeloma plasma cells only secrete paraproteins with light chains and don’t produce heavy chains.
What is non-secretory myeloma?
Paraproteins and light chains aren’t detected in the blood; diagnosis is made by bone marrow biopsy.
What does a skeletal survey include?
A set of x-rays of multiple skeletal sites including skull, long bones, digits, spine, ribs.
What will a skeletal survey show in myeloma?
Lytic lesions, pathological fractures, and pepper pot skull.
What do kidney function tests reveal in myeloma?
High creatinine and urine protein electrophoresis (UPEP) to detect Bence-Jones proteins.
What does a full blood count (FBC) show in myeloma?
Anaemia.
What is the serum calcium level in myeloma patients?
Increased.
What is the management for renal failure?
IV fluids and dialysis
What is the management for hypercalcemia?
IV fluids and bisphosphonates
What is the management for pain?
Analgesia, radiotherapy for bones affected
What is the management for fractures?
Radiotherapy or surgery
What is the management for spinal cord compression?
Steroids and radiotherapy
What is the management for anaemia?
Blood transfusion or EPO transfusion
What is the management for infections?
Antibiotics
What is the management for psychological distress due to insurability?
Psychological support
What is the chemotherapy protocol for patients over 70 years old?
They will receive chemotherapy only
What is the chemotherapy protocol for patients younger than 70 years old?
They will have chemotherapy followed by high dose chemotherapy and autologous stem cell transplant
How are stem cells harvested for transplantation?
Stem cells are harvested from patient blood or bone marrow, concentrated, and cryopreserved
What is the purpose of high doses of chemotherapy in myeloma treatment?
To kill off as much myeloma as possible
What is an example of a drug with high efficacy in myeloma treatment?
Thalidomide
Thalidomide has been used since 1999 and can be used as monotherapy or with other chemotherapies.
What are some side effects of thalidomide?
Neuropathy, venous thrombosis, sedation, constipation, phocomelia (birth defects)
What are more potent alternatives to thalidomide?
Lenalidomide or pomalidomide
These cause less constipation, sedation, and neuropathy but are immunomodulatory and anti-angiogenic.
What is daratumumab used for?
It targets anti-CD38 antibody expressed by plasma cells
What are examples of proteasome inhibitors effective against myeloma?
Bortezomib, carfilzomib, and ixazomib
These are often used in combination with steroids.
What is Monoclonal Gammopathy of Undetermined Significance (MGUS)?
MGUS is characterized by a paraprotein level lower than myeloma (30g/L), usually less than 10g/L, and is an incidental finding.
What is the percentage increase of bone marrow plasma cells in MGUS?
Bone marrow plasma cells have increased by less than 10%.
What are the CRAB criteria in relation to MGUS?
There are no CRAB criteria or end organ damage in MGUS.
In which age group is MGUS most common?
MGUS is rare in young people but common in people over 80 years old.
What is the treatment approach for MGUS?
The treatment is to watch and wait until CRAB symptoms occur or the patient has an abnormal light chain ratio.
What is a Plasmacytoma?
Plasmacytoma manifests as a solitary plasmacytoma of bone or solitary extramedullary plasmacytoma in soft tissues.
How is a localized plasmacytoma treated?
It is treated with high dose radiotherapy if it is truly localized and has no underlying myeloma.
What type of paraproteins do low-grade lymphomas produce?
Lymphoma cell clones produce IgM paraproteins.
What are the clinical features of low-grade lymphoma?
Patients will present with clinical features of lymphoma.
What additional risk is associated with IgM paraproteins?
There is an additional risk of hyperviscosity due to the large pentameric IgM molecule.
What is primary amyloidosis?
Primary amyloidosis is a protein conformation disorder where clonal plasma cells make light chain fragments deposited in organs as insoluble amyloid protein.
What is the prognosis for untreated primary amyloidosis?
The prognosis is 12-14 months if untreated.
Which organs are most commonly affected by amyloidosis?
Amyloidosis can affect any organ but most commonly affects the heart, kidneys, peripheral nerves, liver, gastrointestinal tract, and skin.
What are the heart-related complications of amyloidosis?
It can cause congestive cardiomyopathy and wall thickening.
What kidney condition can result from amyloidosis?
It can cause nephrotic syndrome (protein leak) with or without renal failure.
What is a common gastrointestinal symptom of amyloidosis?
Macroglossia (enlarged tongue) and malabsorption.
What is the investigation method for amyloidosis?
Tissue biopsy to show affected organs, e.g., renal biopsy shows Congo red stain with characteristic apple-green birefringence.
What does a subcutaneous fat aspirate show in amyloidosis?
It shows where amyloid usually deposits.
How does amyloidosis due to myeloma differ from primary amyloidosis?
Amyloidosis due to myeloma will show plasma cell increase by at least 10% in bone marrow.
What is the management for amyloidosis?
Organ specific supportive treatment and treatment of underlying cause with chemotherapy used for myeloma.
What effect does chemotherapy have on amyloidosis?
Chemotherapy treats plasma cell clones instead of amyloid itself and will cause gradual regression of amyloid.
