MULTIPLE MYELOMA Flashcards
What is multiple myeloma?
A heterogenous group of conditions characterised by disordered proliferation of plasma cells and hence associated with the presence of monoclonal immunoglobulins in the serum or urine.
What age group are most often affected by multiple myeloma?
Elderly. Very rare before 40, but 3 in 10,000 in over 80s.
What is the pathogenesis of multiple myeloma?
Arises in a post-germinal centre B lymphocyte in a lymph node or the spleen. The neoplastic cells then move to the bone marrow where the environment facilitates plasma cell proliferation. This causes bone marrow failure.
How are bones affected in multiple myeloma?
Osteoblasts are inhibited as in the secretion of osteoprotogerin (OPG). As a result, osteoclasts are no longer inhibited and there is lytic destruction of the bone.
What is the most common type of monoclonal paraprotein found in multiple myeloma patients?
IgG - 60% of patients
IgA - 20-25%
What are the renal complications of multiple myeloma?
Renal failure as a result of hyperviscosity of the blood, protein deposition in renal tubules, hypercalcaemia and amyloid.
Which ethnic group are most at risk of developing multiple myeloma?
Afro-Caribbean
What are the complications of multiple myeloma?
Bone pain Osteolytic lesions leading to fracture Anaemia Bleeding Hypercalcemia Acute kidney injury Infection Spinal cord compression Neuropathy
What percentage of all cancers does multiple myeloma make up?
1%
Is there a familial link to multiple myeloma?
Cases of familial multiple myeloma are extremely rare.
What are the classic symptoms of multiple myeloma?
Weight loss Fatigue Bone pain Bleeding Back ache Swollen ankles Infection Impaired vision
What is the most common presenting complaint which eventually leads to a diagnosis of multiple myeloma?
Bone pain
What investigations would you order for someone with suspected multiple myeloma?
FBC ESR U&Es GFR Plasma viscosity Blood film Serum electrophoresis - Look for M protein and immunoglobulins Urine electropheresis Bone marrow aspirate X-ray/CT/MRI - skeletal survey
What might the blood tests of someone with multiple myeloma show?
Normochromic normocytic anaemia Neutropenia Thrombocytopenia Raised ESR High calcium Normal alkaline phosphotase (suppressed osteoblast activity) High viscosity Renal dysfunction Presence of paraprotein Low albumin (advanced disease)
What might the blood film of someone with multiple myeloma show?
Rouleaux formation
What is the most sensitive imaging technique for myeloma?
MRI
What percentage of multiple myeloma patients develop amyloid? What are the complications?
10%
Renal failure
Cardiac failure
Neuropathy
How do assess for amyloid deposition?
Serum amyloid P scanning
What are the important differential diagnoses in someone with suspected multiple myeloma?
Monoclonal gammopathy of undetermined significance (MGUS)
Smouldering multiple myeloma
How might you differentiate between multiple myeloma or monoclonal gammopathy of undetermined significance?
No single differentiating test although serum IgG concentration over 30g/L is more suggestive of multiple myeloma.
What is the immunoglobulin light chain protein found in the urine of multiple myeloma patients?
Bence Jones protein
How does kidney injury lead to anaemia in multiple myeloma patients?
Renal failure leads to reduced production of EPO which in turn leads to anaemia.
Why is it not enough to test the urine just by doing a simple dipstick for someone with suspected multiple myeloma?
Urine dipstick tests for the presence of albumin. The large amount of protein being deposited in the urine in a MM patient is immunoglobulins. To visualise the protein in the urine you can add sulfosalicylic acid to the sample. Alternatively you can just order a urine electrophoresis.
What are the two types of acute kidney injury that may occur as a result of multiple myeloma?
Light chain cast nephropathy (myeloma kidney)
Light chain amyloidosis
Which type of acute kidney injury associated with multiple myeloma (either light chain cast nephropathy or light chain amyloidosis) will produce a positive result on a urine dipstick?
Light chain amyloidosis due to loss of albumin
Why do you get Rouleaux formations in a multiple myeloma patient?
Hyperviscosity of the blood due to immunoglobulins
How are the bone lesions caused by multiple myeloma described on a bone survey?
Punched out lytic lesions
How is beta-2 microglobulin related to prognosis in multiple myeloma patients?
Raised beta-2 microglobulin is a poor prognostic sign
What are the three criteria for a diagnosis of multiple myeloma?
M protein in the serum or urine 10% or greater clonal plasma bone marrow cells Organ impairment: CRAB Calcium level Renal insufficiency Anaemia Bone lytic lesions
What criteria differentiate multiple myeloma from monoclonal gammopathy of undetermined significance (MGUS)?
In MGUS:
Serum monoclonal IgG, IgA or IgM is less than 3 g/dL
Clonal bone marrow plasma cells are less than 10%
No organ impairment damage (CRAB)
What criteria differentiate multiple myeloma from smouldering multiple myeloma?
No organ impairment (CRAB)
What are the initial chemotherapy options for multiple myeloma?
Lenilidamide
Valcade
Melphalan and prednisolone
Dexamethasone
Infusion chemo: Vincristine, adriamycin plus methylprednisolone or dexamethasone
Investigational therapy: bortezomib, adriamycin and dexamethasone
What reduction in paraprotein do most multiple myeloma patients achieve with melphalan?
More than 50%
What drugs may be used to prolong the plateau phase of multiple myeloma?
Interferon-alpha
Thalidomide
In addition to the chemotherapy and steroids, what drug might you want to give a multiple myeloma patient experiencing bone lytic lesions?
Bisphoshonates
