Haem Malignancy- Myeloma Flashcards
What is myeloma?
- Haem malignancy characterised by plasma cell proliferation
- Arises due to genetic muttions which occur as B-lymphocytes differentiate into mature plasma cells
- Occurs for around 1% of all cancers
What is myeloma?
- Haem malignancy characterised by plasma cells proliferation- results in large quantities of a single type of antibody being produced
- Arises due to genetic mutataion which occur as B-lymphocytes differentiate into mature plama cells
What is Monoclonal gammopathy of undetermined significance?
- Excess of a single type of antibody or antibody components without other features of myeloma or cancer
- Often incidental finding in otherwise healthy person
- May progress to myeloma and pts often followed up routinely to monitor for progression
Pathophysiology of Myeloma?
- Plasma cells genetically mutated so they multiply rapidly and uncontrollably
- These plasma cells produce one type of antibody/ immunoglobulins
- When you measure immunoglobulins in a pt w myeloma one type of antibody (A,G,M,D,E) will be significantly abundant
- More than 50% of the time it is IgG
- This single type of antibody that is produced by all the identical plasma cells can be called monoclonal paraprotein
What are Bence Jones protein?
- Found in urine of many pts with myeloma
- subunit of the antibody-light chains
What is the monoclonal paraprotein in myeloma?
- The single type of antibody that is produced by all the identical cancerous plasma cells
What age does myeloma present?
- Median age is 70 years old
What are the clinical features of myeloma?
Just state them, will go into more detail in later q;s
Mnemoic CRABBI
- Calcium- hypercalcaemia
- Renal- Renal damage/failure
- Anaemia- causing fatigue and pallor
- Bleeding
- Bones- bone pain and increased risk of pathological fractures
- Infection- more susceptible
Cause and presentation of hypercalcaemia in myeloma?
- primary factor: due primarily to increased osteoclastic bone resorption caused by local cytokines (e.g. IL-1, tumour necrosis factor) released by the myeloma cells- leads to osteolytic lesions
- much less common contributing factors: impaired renal function, increased renal tubular calcium reabsorption and elevated PTH-rP levels
- this leads to constipation, nausea, anorexia and confusion
Cause and presentation of renal damage in myeloma?
- monoclonal production of immunoglobulins results in light chain deposition within the renal tubules
- this causes renal damage which presents as dehydration and increasing thirst
- other causes of renal impairment in myeloma include amyloidosis, nephrocalcinosis, nephrolithiasis
Cause and presentation of anaemia in myeloma?
- bone marrow crowding suppresses erythropoiesis leading to anaemia
- this causes fatigue and pallor
Cause and presentation of bleeding in myeloma?
- bone marrow crowding also results in thrombocytopenia which puts patients at increased risk of bleeding and bruising
Cause and presentation of bone pain in myeloma?
- bone marrow infiltration by plasma cells and cytokine-mediated osteoclast overactivity creates lytic bone lesions
- this may present as pain (especially in the back) and increases the risk of pathological fractures
Cause of increased infection risk in myeloma?
a reduction in the production of normal immunoglobulins results in increased susceptibility to infection
The most common infections are respiratory and urinary.
* * Patients are also more susceptible to viral infections. These infections need to be recognised and treated quickly, as they can often progress rapidly.
* * Some patients with particularly low levels of immunoglobulins can have intravenous immunoglobul
Other features of myeloma?
NOT CRABBI
- Amyloidosis
- Carpal tunnel syndrome
- Neuropathy
- Hyperviscosity
What are the symptoms of hyperviscosity?
- Easy bruising
- Easy bleeding
- Reduced or loss of sight due to vascular disease in the eye
- Purple discolouration to the extremities (purplish palmar erythema)
- Heart failure
RF for myeloma?
- older age
- Male
- Black african
- family hx
- obesity
When should you consider myeloma?
- Anyone over 60 with persistent bone pain, particularly back pain, or unexplained fractures
What initial invesigations would you perform to rule out/in myeloma?
- FBC- low WCC in myeloma
- Calcium- raised in myeloma
- ESR- raised in myeloma
- Plasma viscosity- raise in myeloma
- Blood film – rouleaux formation (red cells stacked on top of each other)
IF any of these are positive or myeloma is still suspected- do an URGENT SERUM PROTEIN ELECTROPHORESIS AND URINE BENCE-JONES PROTEIN
What specific lab investigations (following the initial ones) would you do if you suspected myeloma?
Mnemonic BLIP
- B- Bence Jones Protein (request urine electrophoresis)
- L-Serum-free Light chain assay
- I-Serum Immunoglobulins
- P-Serum protein electrophoresis
Bone marrow biopsy is necessary to confirm the diagnosis of myeloma and get more info on the disease
What imaging do you do for myeloma?
Required to assess for bone lesions
* Whole body MRI
* Whole body CT
* Skeletal survey
Patients only require one investigation but may not tolerate or be suita
above is order of preference
What are the criteria for myeloma diagnosis?
Diagnostic criteria for multiple myeloma requires one major and one minor criteria or three minor criteria in an individual who has signs or symptoms of multiple myeloma.
Major criteria
* Plasmacytoma (as demonstrated on evaluation of biopsy specimen)
* 30% plasma cells in a bone marrow sample
* Elevated levels of M protein in the blood or urine
Minor criteria
* 10% to 30% plasma cells in a bone marrow sample.
* Minor elevations in the level of M protein in the blood or urine.
* Osteolytic lesions (as demonstrated on imaging studies).
* Low levels of antibodies (not produced by the cancer cells) in the blood.
*
What is plasmacytoma?
- Individual tumours made up of the cancerous plasma cells
- Can occur in bones, replacing normal bone tissue or can occur outside bones in the soft tisue of the body
Xray signs in myeloma?
- Punched out lesions
- Lytic lesions
- “Raindrop skull” caused by many punched out (lytic) lesions throughout the skull that give the appearance of raindrops splashing on a surface
What is the aim of treatment in Myeloma?
- Control disease
- Usually takes relapsing and remitting course
- Aim to improve quality and quantity of life
- MDT approach
What is the first line treatment of myeloma?
- Combination of chemotherapy with:
- Bortezomid
- Thalidomide
- Dexamethsone
Side effects of steroids
- Weight gain
- Insulin resistance
- Cushings
- Hirsuitism
- Thin skin
- Easy bruising
- Insomnia
- Bone weakness/osteoporosis
Aside from chemotherapy, what adjuncts to treatment are there in myeloma?
- Stem cell transplanatation can be used as part of clinical trial where pts are suitable
- VTE prophylaxis
- Manage myeloma bone disease following:
Bisphosphonates- these suppress osteoclast activity
Radiotherapy- to bone lesions can improve bone pain
Orthopaedic surgery- can stabilise bones
Cement augmentation- invovled injecting cement into vertebral fractures or lesions- can improve spine stability and pain
Complications of myeloma?
- Infection
- Pain
- Renal failure
- Anaemia
- Hypercalcaemia
- Peripheral neuropathy
- Spinal cord compression
- Hyperviscosity
How many patients with MGUS develop myeloma?
- Around 10% of pts eventually develop myeloma at 10 years
- 50% at 15 years
Features of MGUS?
- Usually asymptomatic
- No bone pain or increased risk of infections
- around 10-30% patients have demyelinating neuropathy
MGUS differentiating features from Myeloma
- Normal immune function
- normal beta-2 microglobulin levels
- lower level of paraproteinaemia than myeloma
- stable level of paraproteinaemia
- no clinical features of myeloma
MGUS differentiating features from Myeloma
- Normal immune function
- normal beta-2 microglobulin levels
- lower level of paraproteinaemia than myeloma
- stable level of paraproteinaemia
- no clinical features of myeloma
What is amyloidosis?
what is it, what is its precusor etc.
- amyloidosis is a term which describes the extracellular deposition of an insoluble fibrillar protein termed amyloid
- amyloid is derived from many different precursor proteins
- in addition to the fibrillar component, amyloid also contains a non-fibrillary protein called amyloid-P component, derived from the acute phase protein serum amyloid
other non-fibrillary components include apolipoprotein E and heparan sulphate proteoglycans
- in addition to the fibrillar component, amyloid also contains a non-fibrillary protein called amyloid-P component, derived from the acute phase protein serum amyloid
- the accumulation of amyloid fibrils leads to tissue/organ dysfuncti
How is amyloidosis classified?
- Systemic or localized
- further characterised by precursor protein (e.g. AL in myeloma - A for Amyloid, L for immunoglobulin Light chain fragments)
Diagnosis of Amyloidosis?
- Congo red staining: apple-green birefringence
serum amyloid precursor (SAP) scan - biopsy of skin, rectal mucosa, or abdominal fat
What is ‘smouldering myeloma”?
Differentiated from symptomatic myeloma by the absence of end-organ damage.
Often these patients do not receive treatment initially.
Instead, a watch and wait approach is adopted, with regular reviews in a haematology clinic.
Patients are monitored for signs of early end-organ damage developing (progression).
If patients begin to develop end-organ damage, treatment is considered.
Criteria for smouldering myeloma?
The below criteria must be met for a diagnosis of asymptomatic (smouldering) myeloma:
Serum paraprotein >30 g/L
+/- Clonal plasma cells >10% on bone marrow biopsy
NO myeloma-related organ or tissue impairment
Prognosis of myeloma?
With high dose chemotherapy followed by autologous stem cell transplantation, the median survival has been estimated to be 4.5 years.
The overall 5-year survival rate is around 35%.
