Multiple Myeloma Flashcards
What is multiple myeloma?
- A blood cancer which develops from the plasma cells in the bone marrow
What are plasma cells?
- Plasma cells are part of the immune system
- They make proteins called antibodies
- Antibodies attack and kill bacteria and viruses so they are able to protect us from infections
What are the 5 main types of antibody?
- IgA
- IgG
- IgM
- IgD
- IgE
Where do plasma cells come from?
- The bone marrow produces stem cells
- Lymphoid stem cells
- Forms a lymphoblast
- Which can be a B or T lymphocyte
- The B lymphocyte produces plasma cells
What are the risk factors for Myeloma?
- Age ( more common in older people)
- Black/ African Decent
- More common in men
- Overweight
- Family History
- Lowered Immunity (HIV, SLE)
- MGUS (Monoclonal gammopathy of undetermined significance)
What is MGUS?
- MGUS excess of a single type of antibody or antibody component without other features of myeloma or cancer
- MGUS doesn’t typically cause any symptoms or need any treatment
- Only a small number of people with MGUS develop myeloma
What are the symptoms of Myeloma?
- Bone Pain
- Broken Bones
- Tiredness (fatigue), SOB = anaemia
- Infections that are consistent
- Nausea and loss of appetite
- Spinal Cord Compression (anywhere in your back/ worse when you cough/ stopping you sleep)
- High Calcium levels (feeling thirsty, passing urine more frequently, confusion and drowsiness)
What is CRAB ?
C - Calcium levels high - due to increased osteoclastic bone resorption caused by cytokine release ( constipation, nausea, poor appetite, abdominal pain, lethargy and confusion)
R - Renal Impairment (light chain deposition in the tubules) - dehydration, polydipsia, Anuria, polyuria, oedema
A - Anaemia (bone marrow infiltration suppresses erythropoioesis )
B - Bone Disease (bone lesions/pain - lytic bone lesions due to infiltration and osteoclast overactivity) - lower back/ pathological fractures
B- Bleeding: thrombocytopenia due to bone marrow infiltrations - bruising
I - Infection: Reduced production of normal immunoglobulins
Hyper-viscosity - blurred vision, headaches, nosebleeds and weight loss
What is Hyperviscosity Syndrome?
- high paraprotein levels
- Blurred vision, headaches, mucosal bleeding and dyspnoea
What is Spinal Cord Compression?
- Compression of the Spinal Cord due to metastasis
When to suspect Myeloma ?
- Unexplained Bone Pain
- Fatigue
- Hypercalcaemia
- Weight loss
- Cord Compression
- Hyperviscosity
- Recurrent infections
What are the symptoms of hypercalcaemia?
- bone pain, abdo pain, constipation, confusion, polyuria
What are the symptoms of cord compression?
- back pain, leg weakness, bladder/bowel dysfunction
What is involved in the screening for myeloma?
- Protein Electrophoresis ( gives us the characterisitic band patterns)
- Immunofixation ( fixes the antibodies in place, important for the identification of proteins after separation by electrophoresis)
- Urine Electrophoresis and serum free light chains ( this looks at the light chains which are secreted)
- Serum immunoglobulins
What typical pattern is seen in protein electrophoresis and Immunofixation for Myeloma?
- IgG, IgA or accompanying light chain
What would you think if you saw IgM monoclonal antibody seen on electrophoresis?
- Suggests Waldenstrom Macroglobulinemia
What is Waldenstrom Macroglobulinemia?
- A type of Non-Hodgkin’s Lymphoma
- Has high bound IgM
What is the results of the Urine Electrophoresis and serum free light chains?
- Looks at the light chains which are unbound to heavy chains
- The most important part is the ratio between kappa and lambda
- An elevated ration is suggestive of myeloma and requires further work-up
- In the urine electrophoresis: light chains are filtered by the kidneys into the urine, these are known as Bence-Jones proteins
What does it mean if patients have non-secretory MM?
- This is when the patient doesn’t have detectable paraprotein levels
What is the Diagnostic Criteria for Multiple Myeloma?
- Monoclonal Protein Present
- Bone marrow plasma cells >10%
- Organ Damage
How are monoclonal antibodies detected?
- Protein electrophoresis & immunoglobulins
- Serum Free Light Chains
+/- urine electrophoresis for Bence-Jones Protein
How is the Bone Marrow Infiltration measured?
- Bone Marrow Aspirate and Trephine with Cytogenetics
How is Myeloma- related organ damage measured?
- FBC, U+E, Bone Profile
- Imaging(whole body MRI)
- Skeletal Survey (X-ray)
- Staging
What is Smouldering?
- This is a precancerous conditions that alters certain proteins in the blood
- Increases plasma cells in the bone marrow
- Does not causes symptoms of the disease
How does Smouldering present?
- Monoclonal protein raised ( M protein)
- Bone Marrow plasma cells raised
- No organ damage
What is MGUS?
- This is a precancerous condition which is a premalignant plasma cell disorder
- It typically affects 3% of patients
- MGUS can progress to MM
How does MGUS present?
- Monoclonal protein low
- Bone Marrow plasma cells less than 10%
- No organ damage
How does MGUS present?
- Monoclonal protein low
- Bone Marrow plasma cells less than 10%
- No organ damage
What are the risk factors for multiple Myeloma?
- Body Weight
- Male Gender
- Age - increases as you get older
- MGUS
- Family History
- Lowered Immunity (HIV, Immunosuppression after an organ transplant )
What blood tests would you do for Multiple Myeloma?
- FBC
- Serum Protein Electrophoresis
- Serum Free Light Chain assay
- Calcium Level
- U+E
- Beta 2 microglobulin
- Albumin Levels
- LFTs
- ESR
- LDH
What blood tests would you do for Multiple Myeloma?
- FBC
- Serum Protein Electrophoresis
- Serum Free Light Chain assay
- Calcium Level
- U+E
- Beta 2 microglobulin
- Albumin Levels
- LFTs
- ESR and Plasma Viscosity = both raised
- LDH
What is Plasmacytoma?
- A tumour made up of plasma cells which come together in a lump
- Patients have a risk of developing Myeloma
- Doctors treat plasmacytoma with radiotherapy
What is Amyloidosis?
- This is a rare condition
- The plasma cells make an abnormal protein called amyloid
- Amyloid collects in body organs (kidneys, heart) and gradually causes damage
- Most develop myeloma
How is myeloma classified?
- Using the International Staging System
- This divides the stages into 3
How doctors classify myeloma?
- Look for signs and symptoms of myeloma ( CRAB)
- Then describe myeloma as symptomatic/ smouldering
Is Multiple Myeloma a curable condition?
- No, it is an incurable condition
What are the treatment principles of myeloma?
- Induction therapy
- ASCT
- Maintenance
- Relapse or refractory disease
What is the Chemotherapy Regime?
- Bortezomid
- Thalidomide
- Dexamethasone
What stem cell transplant is used in Myeloma?
- Autologous
- High dose chemotherapy and then their own stem cells are given
What is Myeloma Bone Disease?
- This is as a result of increased osteoclast activity and suppressed osteoblast activity
- This means more bone is being reabsorbed
- This causes cytokines to be released from the plasma cells and the stromal cells
Where do you typically see Myeloma Bone Disease?
- Skull
- Spine
- Long bones
- Ribs
- These are patches of thin bone that can be described as osteolytic lesions
- These lead to pathological fractures
What is Myeloma Renal Disease?
- High levels of immunoglobulins/ antibodies in the blood can block the flow through the tubules
- Hypercalcaemia impairs renal function
- Dehydration
- Meds such as bisphosphonates
What causes Hyperviscocity of the blood?
- When there are increased proteins like immunoglobulins and fibrinogen in the blood
- This increases the plasma viscosity
What are the symptoms of plasma viscosity?
- Easy bruising
- Easy bleeding
- Reduced/ loss of sight due to vascular disease in the eye
- Purple discolouration to the extremities
- Heart Failure
What are the 4 important investigations for myeloma?
B L I P
- Bence- Jones Proteins
- Serum- free Light chain assay
- Serum Immunoglobulins
- Serum Protein Electrophoresis
What further investigations are required?
- Bone Marrow Biopsy
- Imaging ( Whole Body MRI, Whole Body CT, Skeletal Survey)
What Bloods should you do if you are suspecting Myeloma?
- FBC
- Calcium
- ESR
- Plasma Viscosity
What X-ray signs do you see in Myeloma?
- punched out lesions
- lytic lesions
- Raindrop Skull
What is the management of Myeloma Bone Disease?
- Bisphosphonates
- Radiotherapy
- Orthopaedic Surgery
- Cement Augmentation ( injecting cement into vertebral fractures/ lesions to improve spine stability and pain
What is benign polyclonal hypogammaglobulinaemia?
- Benign condition that does not progress to malignancy
- Immune system makes too many immunoglobulins
