[12] Myeloma Flashcards
What kind of cancer is myeloma?
Haematological
What is the prevalence of myeloma in the UK?
4 in 1000
Is myeloma more common in men or women?
Equal
What ethnicity is myeloma more common in?
Afro-Caribbean populations
What is the principle risk factor for myeloma?
Age
At what age do most cases of myeloma occur?
65 or older
At what age is myeloma rare?
Patients under 35
What kind of cells does myeloma arise in?
B-cells
What is myeloma caused by?
Clonal proliferation of mature plasma cells that secrete immunoglobulins or fragments of
In what % of myeloma patients are karyotype abnormalities found?
50%
What molecular abnormalities are recognised in myeloma?
- 14q32 translocations
- Chromosome 13 deletions
- FGFR3 activation
What is characteristically produced in myeloma?
Paraprotein
How is paraprotein produced in myeloma?
The clonal population undergo immunoglobulin class switching and somatic hypermutation, leading to the overproduction of a single immunoglobulin class, referred to as paraprotein
What happens to the plasma cells once they have mutated in myeloma?
They typically migrate to the bone marrow, causing bone marrow infiltration
What produces osteolysis and destructive bone lesions in myeloma?
Dysregulation of the osteoprotegrin rankl system by tumour-secreted cytokines
How does myeloma often present?
Significant bone pain
What causes the bone pain in myeloma?
Destructive lytic lesions or pathological fractures
What other bone pathology is common in myeloma?
Vertebral collapse
What might vertebral collapse lead to in myeloma?
Spinal cord compression, which is an emergency
Other than bone symptoms, how might myeloma present?
Vague symptoms, including;
- General malaise
- Aches and discomfort
- History of repeated infection
What causes the general malaise in myeloma?
Anaemia
How is myeloma increasingly diagnosed?
Due to an incidental finding on blood count, with pancytopenia or anaemia
What are the important red flags for myeloma?
- Unexplained back pain
- Night sweats
- Weight loss
- Extreme lethargy
What complications may be presenting features of myeloma?
Renal impairment and progressive renal failure
What causes renal impairment and progressive renal failure in myeloma?
Amyloidosis or deposition of paraprotein in the kidneys
Why might patients with myeloma develop atypical infections?
Due to pancytopenia
What initial investigations are required in suspected myeloma?
- FBC
- Measurement of ESR
- Serum protein electrophoresis
What is the most common finding on FBC in myeloma?
- Normocytic, normochromic anaemia of chronic disease
- Anaemia or pancytopenia due to marrow infiltration
What happens to ESR in myeloma?
Raised
What is found on urine and plasma electrophoresis for immunoglobulins in myeloma?
A monoclonal paraprotein band
What happens in some forms of myeloma, regarding paraprotein?
Paraprotein will only appear in the urine in the form of Bence Jones protein
What should serum biochemistry investigate in myeloma?
- Renal function
- ß2 microglobulin levels
- Alkaline phosphatase levels
What might raised alkaline phosphatase levels in myeloma indicate?
Bone involvement
What metabolic abnormality is common in myeloma?
Hypercalcaemia
What might examination of the peripheral blood film show in myeloma?
Formation of rouleaux
What are the formation of rouleaux associated with?
Very high ESR
Where should patients be referred for further investigations for myeloma?
Haematologist
What further investigations will haematologists do in myeloma?
Bone marrow aspirate and trephine
What is typically found on bone marrow aspirate and trephine in myeloma?
More than 20% plasma cells
What are the plasma cells on bone marrow aspirate positive for in myeloma?
- CD138
- Cytoplasmic immunoglobulin (cIg)
What are the plasma cells on bone marrow aspirate negative for in myeloma?
- CD5
- CD20
- Surface immunoglobulin (sIg)
What do normal plasma express?
CD19
Do malignant plasma cells in myeloma express C19?
No
Why do malignant plasma cells not express CD19?
Possibly related to the loss of PAX5 gene expression
Do malignant plasma cells express CD10?
Most do not, but may be present in advanced disease
How can monoclonality be demonstrated in myeloma?
By immunoperoxidase staining with κ
and λ antibodies and cytogenetic analysis
What sites need to be x-rayed in myeloma?
Any sites of bone tenderness
How can x-rays be used to direct treatment in myeloma?
Can direct subsequent radiotherapy
What is a skeletal survey required for in myeloma?
To assess the extent of bone disease
What is the limitation of bone scans in myeloma?
They are not helpful for detection because they demonstrate osteoblastic activity, but myeloma stimulates osteoclastic activity and is therefore not seen on a bone scan
Why might hotspots be seen on bone scans in myeloma?
Due to pathological fractures
What should the initial treatment of myeloma be directed at?
Correction of renal function abnormalities and hypercalcaemia
What management steps should be taken in the initial treatment of myeloma?
- Start patient on allopurinol
- May require hydration and transfusion
What may be required in the management of myeloma when there is significant bone pain?
Opiates and radiotherapy
What is the aim of treatment of myeloma?
Induce remission
What is the induction of remission in myeloma referred to?
Plateau
Is myeloma likely to recur after treatment?
Yes
What is done as a result of myeloma being likely to recur after treatment?
Watchful waiting is adopted for surveillance after treatment
Why is watchful waiting adopted for surveillance of myeloma after treatment?
Because there is no benefit from early intervention
What is usually used for direct tumour of myeloma?
Chemotherapy
What is the purpose of chemotherapy in myeloma?
Complete remission
What are the side effects of thalidomide (chemotherapy used in myeloma)?
- Constipation
- Peripheral neuropathy
- Increased thrombotic risk
- Teratogenic effects
What should patients be considered for if complete remission is achieved in myeloma?
Autologous stem cell transplantation
Why should autologous stem cell transplantation be considered in patients with complete remission from myeloma?
Can prolong disease free interval
What is considered in the management of more resistant cases of myeloma?
Allogenic stem cell transplantation
What needs to be weighed when considering allogenic stem cell transplantation for the treatment of myeloma?
Usage must be carefully weighed against risk to the patient
What supportive therapy may be used in myeloma?
- Radiotherapy
- Blood transfusions
- Immunisations
- Early intervention for bone disease
What is radiotherapy used to treat in myeloma?
- Localised lytic lesions
- Bone pain
- Spinal cord compression
What are blood transfusions used to treat in myeloma?
Anaemia
What is the purpose of immunisations in myeloma?
Protect against common pathogens
What is the purpose of early invention for bone disease in myeloma?
Prevent fractures
What is involved in early intervention for bone disease in myeloma?
- Use of bisphosphonates
- Percutaneous vertebroplasty
What more recent develops have been made in the treatment of myeloma?
- Proteasome inhibitors
- Thalidomide derivatives
Is myeloma curable?
No
Why is myeloma not curable?
In all cases, it will inevitably reoccur and become increasingly more resistant to therapeutic options, with second and third line therapies conferring more risk to the patient
What is the average 5 year survival rate for myeloma?
35%
