Multiple Myeloma Flashcards
What is multiple myeloma a disease of?
Plasma cells (proliferation)
- fill up the bone marrow
- produce aberrant antibodies (immunoglobulins)
It is the …. most common haematological malignancy
Second
What is the median age at presentation?
70
But 10-15% are less than 45
Who is it more common in?
Men
Black Africans
What causes myeloma?
Genetic mutations - occurs as B lymphocytes differentiate into mature plasma cells (HLA Cw5 or Cw2 May play role)
Defects that carry poor prognosis: chromosome 13 abnormalities, p53 deletions
Environmental- exposure to agricultural, food, petrochemical industries, long term hair dye exposure
Radiation
MGUS - approx 19% develop MM
A typical antibody is composed of…
2 immunoglobulin (Ig) heavy chains 2 immunoglobulin (Ig) light chains
What 5 heavy chain isotypes are there?
MAGED
What 2 light chain isotypes are there?
Kappa
Lambda
What are the abnormal antibodies produced in myeloma called?
Paraproteins (also called M protein/ M spike / monoclonal gammopathy)
What is the most common immunoglobulin abnormality in multiple myeloma?
IgGk (55%)
How is myeloma classified?
Based on Ig product
IgG in 2/3
IgA in approx 1/3
Few are IgM or IgD
Other Ig levels are low (increased infection susceptibility)
What is Bence Jones proteinuria?
Free Ig light chains of kappa or lambda filtered by kidneys into urine
Usually light chains synthesised in excess and cleared by kidney - normally less than 10mg/ day. In MM more than 10mg/ day
Is Bence Jones proteinuria detected by traditional urine dipstick?
No - only detects albumin proteins
What does serum electrophoresis of plasma proteins show in MM?
Increased gamma globulins = monoclonal spike (M spike)
What can immunoelectrophoresis tell you?
Which type of immunoglobulin is abundant
What type of immunity is affected?
Humoral immunity - so increased risk of infection by staphylococcus aureus, e-coli etc
NOT viruses
How does it present?
CRABBI
C - hypercalcaemia R - renal failure A - anaemia B - bleeding B - bone pain I - infection risk
Why does hypercalcaemia occur?
Increased osteoclast activity with no corresponding increase in osteoblast activity - causing LYTIC lesions
Myeloma cells stimulate the production of specific cytokines that stimulate osteoclast activity. What are they?
IL-6 and RANK ligand
Where do the lytic lesions typically occur?
Skull
Vertebrae
What symptoms are associated with hypercalcaemia?
Weakness Nausea Constipation Confusion Polyuria and polydipsia
The bone destruction can lead to…
Pathological Fractures
Spinal cord compression
What causes the renal impairment?
Combination of factors: Obstruction due to Bence Jones proteins Direct toxicity of the light chains Hypercalcaemia Hyperuricaemia Long term use of NSAIDS can cause damage to kidneys
Renal failure occurs in what percentage of patients?
20-30%
What symptoms /signs can renal failure cause?
Oedema SOB Nausea and vomiting Weight loss Lethargy
What type of anaemia occurs?
Normocytic and normochromic
How frequently is anaemia a symptom?
70% of patients
Why does anaemia occur?
The bone marrow is infiltrated by malignant cells
Also get neutropenia and thrombocytopenia
Where does bone pain most often occur?
Back due to vertebral lytic lesions
What imaging detects the lytic lesions?
X-ray (bone scan not effective as osteoblasts not stimulated)
Why do patients get recurrent bacterial infections?
Immunoparesis
Neutropenia from disease process and due to chemotherapy
What infections are most commonly seen?
Pneumonia
Pyelonephritis
Why can hyperviscosity occur?
Increased circulating immunoglobulins
What can hyperviscosity cause?
Spontaneous bleeding - gums, epistaxis, rectal Visual changes Vertigo Headaches Reduced cognition
How can hyperviscosity be treated?
Plasmapheresis to remove light chains
What blood tests should be requested?
FBC - normocytic normochromic anaemia, WCC and platelets normal or low
U&E - raised urea and creatinine, hypercalcaemia
CRP - raised
ESR persistently raised
LFTS especially for ALP - usually normal as osteoblasts not activated
Other than bloods, what other investigations should be done?
Serum or urine electrophoresis - raised concentration of monoclonal IgG/IgA present (in urine they are known as Bence Jones proteins)
Immunoelectophoresis
Bone marrow aspiration and trephine biopsy confirms diagnosis if number of plasma cells significantly raised
What tests are useful prognostic indicators?
LDH
Beta 2 microglobulin
What imaging is done?
Skeletal survey - plain X-ray showing “pepper pot” appearance
MRI whole body to detect lesions not seen on X-ray
What does a blood film show?
Rouleaux formations = RBCs stacking together
What is the diagnostic criteria?
1) Monoclonal protein band in serum or urine electrophoresis
2) Increased plasma cells on marrow biopsy
3) Evidence of end organ damage - hypercalcaemia, renal damage, anaemia
4) bone lesions
Why is it important to accurately diagnose myeloma?
Treatment must begin immediately due to risk of complications occurring as a result of end organ damage
Is myeloma considered curable?
No , a chronic relapsing and remitting malignancy
Management aims to control symptoms, reduce complications and prolong survival
In younger, healthier patients, how is it managed?
Induction therapy: bortezomib (chemotherapy) plus dexamethasone
Then autologous stem cell transplant
In those unsuitable for transplantation, induction therapy is typically continued for how long and what does it consist of?
12-18 months or until paraprotein level plateaued
Consists of: thalidomide and alkylating agent plus dexamethasone
Do patients often relapse after initial therapy?
Yes, need 3 monthly monitoring - bloods, electrophoresis
If occurs - Bortezomib monotherapy
How should bone pain be managed?
Analgaesia- not NSAIDS
Zolendronic acid to all patients - reduce fracture rates and bone pain
How can anaemia be managed?
Transfusion
EPO
How can renal failure be managed?
Rehydrate
Dialysis may be needed if acute
How should infections be managed?
Annual influenza vaccination
Immunoglobulin replacement therapy
Treat rapidly with broad spec antibiotics until culture results known
