Multiple Myeloma Flashcards
Haemapoietic stem cell seperates into what?
Lymphoid and myeloid stem cell, NK cells
Lymphoid stem cell gives us what
T and B lymphocyte
Myeloid stem cells give us what
Eryhtrocyte
Platelets
Mast cell
Eosinophil
Polymorph
monocyte
osteoclast
Different types of leukaemia
Acute myeloid leukaemia
Acute lymphoblastic leukaemia
Chronic myeloid leukaemia
Chronic lymphocytic leukaemia
Acute leukaemia
– primitive early cells – high proliferative rate – chemo targets cell in division
Chronic leukaemia
lower proliferative rate – insensitive to chemo
What is a myeloma?
Bone marrow cancer
Cancer of differentiated B-lymphocytes, known as plasma cells
What is a multiple myeloma?
is where the myeloma affects multiple areas of the body.
Features of multiple myelomas
- The accumulation of malignant plasma cells in the bone marrow leading to progressive bone marrow failure
- The production of a characteristic paraprotein
- Kidney failure
- Destructive bone disease and hypercalcaemia
What are multiple myelomas assosciated with?
devastating osteolytic bone disease charcterised by:
Osteoporosis
Pepper pot skull
Punch through lesions
Mechanisms include an increase in bone resorption, decrease in bone formation and an uncoupling of resorption and formation leading to rapid bone loss.
What is the pneumonic for melanoma signs and symptoms?
SPIKEY OLD CRAB
C
Calcium
Ca>0.25mmol/l above upper limit of normal or >2.75mmol/l
R
Renal
renal impairment, creatinine>173mmol
Pathogenesis and treatment of renal failiure in multiple myeloma
A
– anaemia
2g <NR or <10g/dl
B
Bone
lytic lesions, osteoporosis compression, spinal cord compression
Problem with myeloma
myeloma remains almost always incurable; it is a remitting, relapsing condition which inexorably progresses to refractory disease and death
Multiple myeloma incidence
10% of all haematological cancers; overall, the second commonest haematological cancer after non-Hodgkins lymphoma
incidence 60-70 per million; approx 4,000 new cases of myeloma per anum in the UK
Median age diagnosis 70 years
Survival ranges from few months to 20 years sometimes
Monoclonal gammopathy of undetermined significance (MGUS)
<30g/dl, <10% plasma cells in the bone marrow, no related organ or tissue impairment (ROTI), no evidence of amyloid or other lymphoproliferative disorder (LPD)
an excess of a single type of antibody or antibody components without other features of myeloma or cancer.
often an incidental finding in an otherwise healthy person - significance unclear.
It may progress to myeloma and patients are often followed up routinely to monitor for progression.
Smouldering myeloma
> 30g/l and/or >10% plasma cells in BM, but no ROTI
20% risk per year of progression in first year, then diminishes to about 5% per year after 5 years and then stabilises
progression of MGUS with higher levels of antibodies or antibody components.
premalignant and more likely to progress to myeloma than MGUS.
Waldenstrom’s macroglobulinemia is a type of smouldering myeloma where there is excessive IgM specifically.
Symptomatic myeloma
diagnostic criteria as evidence of related organ or tissue impairment (ROTI) or amyloid
Is MGUS common?
Yes
present in 3% people aged 50, 5% aged 70 – 1% risk per year of progression; majority of cases of MM present de novo but now recognised that most have had a preceding MGUS phase
Pathophysiology of myeloma
accumulation of malignancy plasma cells in the bone marrow> production of paraprotein [increased amount of plasma protein]> increased proteinuria [protein in urine]> renal disease + destruction bone disease
Pathophysiology of myeloma and antibodies:
When you measure the immunoglobulins in a patient with myeloma, one of those types will be significantly abundant.
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.
How does the destructive bone disease happen?
increased plasma cells 🡪 osteoclasts 🡪 increased bone degraded
Signs and symptoms of multiple myeloma:
hypercalcaemia
tiredness
malaise
increased susceptibility to fractures
opportunistic infections. CRAB
Investigations for myelomas:
Urine electrophoresis
Serum electrophoresis - IgG or IgA
BM aspirate + trephine biopsy
FBC - low WBC
Imaging - whole body MRI, xray
Types of antibodies:
IgG, IgA, IgD, IgM, IgE
GAYMED
Features of antibodies:
antibodies have 2 heavy chains & 2 light chains [kappa & lambda] therefore myeloma are classified by the type of light & heavy chain produced [some people only have light chain myelomas]
Treatment approach of multiple myelomas:
Diagnosis:
1. Asymptomatic myeloma > regular monitoring
2. Symptomatic myeloma > Candidate for stem cell transplant > Yes: Induction treatment, stem cell transplant/ No: non-intensive drug treatment
What is bone marrow infiltration?
cancerous plasma cells invade the bone marrow.
How does bone marrow infiltration cause anaemia?
causes suppression of the development of other blood cell lines leading to anaemia (low red cells), neutropenia (low neutrophils) and thrombocytopenia (low platelets). PANCYTOPENIA
What do osteoclasts do?
Osteoclasts absorb bone
What do osteoblasts do?
osteoblasts deposit bone
What happens in myeloma bone disease?
result of increased osteoclast activity and suppressed osteoblast activity.
caused by cytokines released from the plasma cells and the stromal cells (other bone cells) when they are in contact with the plasma cells.
What are the common places for bone disease to happen?
skull, spine, long bones and ribs
What are osteolytic lesions?
in some areas the bone becomes very thin whereas others remain relatively normal.
these weak points in bone lead to pathological fractures
Hypercalcaemia in myeloma
All the osteoclast activity causes a lot of calcium to be reabsorbed from the bone into the blood. This results in hypercalcaemia (high blood calcium).
Plasmacytomas
These are individual tumours made up of the cancerous plasma cells.
They can occur in the bones, replacing normal bone tissue or can occur outside bones in the soft tissue of the body.
Why do we get renal impairment in myelomas?
High levels of immunoglobulins (antibodies) can block the flow through the tubules
Hypercalcaemia impairs renal function
Medications used to treat the conditions such as bisphosphonates can be harmful to the kidneys
Why is plasma viscosity higher in myelomas?
Plasma viscosity increases when there are more proteins in the blood.
These are proteins like immunoglobulins and fibrinogen, both of which increase with inflammation.
In myeloma there are large amounts of immunoglobulins in the blood causing the plasma viscosity to be significantly higher.
What issues does plasma viscosity cause?
- Easy bruising
- Easy bleeding
- Reduced or loss of sight due to vascular disease in the eye
- purplish palmar erythema
- Heart failure
Risk factors
Older age
Male
Black African ethnicity
Family history
Obesity
Suspecting myeloma
FBC (low white blood cell count in myeloma)
Calcium (raised in myeloma)
ESR (raised in myeloma)
Plasma viscosity (raised in myeloma)
If any of these are positive or myeloma is still suspected do an urgent serum protein electrophoresis and a urine Bence-Jones protein test.
Myeloma testing (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 information on the disease.
Imaging for bone lesions:
1.Whole body MRI
2.Whole body CT
3.Skeletal survey (xray images of the full skeleton)
Patients only require one investigation but may not tolerate or be suitable for MRI or CT.
X-ray 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
First line treatment:
First line treatment usually involves a combination of chemotherapy with:
Bortezomid
Thalidomide
Dexamethasone
When can stem cell transplantation be used?
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.
Management of myeloma bone disease:
Myeloma bone disease can be improved using bisphosphonates. These suppress osteoclast activity.
Radiotherapy to bone lesions can improve bone pain.
Orthopaedic surgery can stabilise bones (e.g. by inserting a prophylactic intramedullary rod) or treat fractures.
Cement augmentation involves injecting cement into vertebral fractures or lesions and can improve spine stability and pain
