9- Haematological malignancy (Myeloma) Flashcards
Myeloma background
is a cancer of the plasma cells. These are a type of B lymphocyte that produce antibodies. Cancer in a specific type of plasma cell results in large quantities of a single type of antibody being produced.
Myeloma accounts for around 1% of all cancers.
Types (based on type of Ig)
o IgG (2/3)
o IgA (1/3)
o IgD and IgM rare
Multiple myeloma
is where the myeloma affects multiple areas of the body
Pathophysiology of myeloma
- Normally a variety of plasma cells produce various forms of Ig, however in myeloma one particular plasma cell clone begins to replicate in an uncontrolled manner -> one specific abnormal Ig will be massively overproduced by the large group of identical plasma cell clones
- Plasma cell clones accumulate in bone marrow, crowding out normal healthy tissue responsible for making normal blood cells
o Anaemia
o Low WBC
o Thrombocytopenia - Plasma cells produce paraprotein
o Abnormal antibody light chains which damage the kidneys by forming protein casts in renal tubule - Also secrete factors which activate osteoclasts -> break down bones -> widespread lytic lesions, bone pain and hypercalcaemia
monoclonal paraproteins
Myeloma is a cancer of a specific type of plasma cell where there is a genetic mutation causing it to rapidly and uncontrollably multiply.
These plasma cells produce one type of antibody. Antibodies are also called immunoglobulins. They are complex molecules made up of two heavy chains and two light chains arranged in a Y shape. They help the immune system recognise and fight infections by targeting specific proteins on the pathogen. They come in 5 main types: A, G, M, D and E. When you measure the immunoglobulins in a patient with myeloma, one of those types will be significantly abundant. More than 50% of the time this is immunoglobulin type G (IgG). This single type of antibody that is produced by all the identical cancerous plasma cells can be called a monoclonal paraprotein. This means a single type of abnormal protein.
The “Bence Jones protein” that can be found in the urine of many patients with myeloma is actually a part (subunit) of the antibody called the light chains.
myeloma RF
- Older age
- Male
- Black African ethnicity
- Family history
- Obesity
potentially precursor conditions of myeloma
MGUS and Smouldering MM
conditions associated with myeloma
- Amyloidosis
- Cryoglobulinemia
investigations for myeloma
Bloods
- FBC: Anaemia, neutropenia, thrombocytopaenia
- Bone profile (calcium raised)
- U&Es
- ESR (raised)
- Plasma viscosity
Blood film: rouleaux formation
Bone marrow biopsy
Imaging to look for lesions (only require one of these)
* Whole body MRI- gold standard
* Whole body CT
* Skeletal survey (xray images of the full skeleton)
Others
- Immunoglobulin measurement
- Protein electrophoresis of blood and urine
- Free light chain levels (paraproteins) (urine Bence-Jones protein)
NICE guidelines for testing for myeloma
BLIP
B – Bence–Jones protein (request urine electrophoresis)
L – Serum‑free Light‑chain assay
I – Serum Immunoglobulins
P – Serum Protein electrophoresis
Xray Signs
- 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
key presentations of myeloma
CRAB
- hyperCalcaemia
- renal failure
- anaemia
- bone lesions
further symptoms of myeloma
- Bone marrow infiltration- pancytopenia
o Anaemia
o Thrombocytopenia
o Neutropoenia - Bone disease- back pain
o Generalised osteopenia
o Lytic lesions
o Pathological fractures - Renal failure
- Neuropathy
- Hyper viscosity e.g. visual disturbance, headache
- Hypercalcaemia (due to breakdown of bone)
o Polyuria
o Polydipsia
o Abdo pain
o Constipation
o Lethargy
o confusion - Impaired immune system
- Bleeding diathesis
- Renal disease
- Can form solid tumours of plasma cells called plasmacytomas
Management of myeloma
The aim of treatment is to control disease. It usually takes a relapsing-remitting course and treatment aims to improve quality and quantity of life. Management will be undertaken by the haematology and oncology specialist multidisciplinary team.
1) First line treatment usually involves a combination of chemotherapy with:
- Bortezomid
- Thalidomide
- Dexamethasone
2) Stem cell transplantation can be used as part of a clinical trial where patients are suitable.
Patients require venous thromboembolism prophylaxis with aspirin or low molecular weight heparin whilst on certain chemotherapy regimes (e.g. thialidomide) as there is a higher risk of developing a thrombus.
more detailed management of myeloma
Initial therapy
- <65
o Initial induction chemotherapy
o Stem cell transplant - > 65
o Most unable to tolerate SCT
o Chemotherapy alone
Maintenance
- Chemotherapy regularly
Relapse
- Very difficult to cure and almost always relapse
- If they relapse undergo re-treatment with original agent or another agent or second autologous stem cell transplant
myeloma and anaemia
The cancerous plasma cells invade the bone marrow. This is described as bone marrow infiltration. This causes suppression of the development of other blood cell lines leading to anaemia (low red cells), neutropenia (low neutrophils) and thrombocytopenia (low platelets).
AL amyloidosis pathophysiology
- the L refers to light chain
- Abnormal plasma cells in bone marrow produce light chains that form amyloid proteins
- Amyloid proteins are only broken down very slowly so start to build up in tissues and organs
- Causes damage and symptoms
