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MULTIPLE MYELOMA
By Lwitiko Mwakagile Amos
Medical Laboratory Scientist
Laboratory QMS Mentor
MULTIPLE MYELOMA
Myel- mean BONE MARROW while –Oma mean
TUMOUR
Multiple myeloma (MM), also known as plasma cell
myeloma, is a cancer of plasma cells, a type of white
blood cell that normally produces antibodies.
The cause of multiple myeloma is unknown.
Risk factors include obesity, radiation exposure,
family history, and certain chemicals
PATHOPHYSIOLOGY
B lymphocytes start in the bone marrow and move to the lymph
nodes.
As they progress, they mature.
When they are activated to secrete antibodies, they are known as
plasma cells
The immune system keeps the proliferation of B cells and the
secretion of antibodies under tight control.
When chromosomes and genes are damaged, often through
rearrangement, this control is lost.
As a result stimulates abnormal antibodies overproduction
NORMAL FORMATION OF BLOOD CELLS
PATHWAYS
ABNORMAL FORMATION OF BLOOD CELLS
PATHWAYS
CAUSE OF MULTIPLE MYELOMA
The cause of multiple myeloma is
generally unknown
But there is various risk factors that
may lead into development of multiple
myeloma
These risk factors are as follows;
1. Monoclonal gammopathy of undetermined
significance (MGUS)
Is a plasma cell disease in which plasma cells
secrete abnormal antibodies called monoclonal
paraproteins or myeloma proteins or M
Proteins(gammopathy), into the blood.
This abnormal protein is usually found during
standard laboratory blood or urine tests.
MGUS resembles multiple myeloma and
similar diseases
Cont….
But the levels of antibodies are lower and the
number of plasma cells in the bone marrow is
also lower.
Rarely has symptoms or major problems
MGUS transforms to multiple myeloma at the
rate of 1% to 2% per year, and almost all cases of
multiple myeloma are preceded by MGUS
2. Smoldering myeloma
Is a disease of plasma cells secreting monoclonal
paraprotein causes the relatively benign disease of
monoclonal gammopathy of undetermined
significance.
This clone proliferates and may slowly evolve into
more aggressive sub-clones that cause smoldering
multiple myeloma.
Further and more rapid evolution causes the
malignant stage of multiple myeloma
Cont….
Smoldering myeloma, however, is not a malignant disease.
It is characterized as a pre-malignant disease that lacks
symptoms
Is associated with bone marrow biopsy showing the presence
of an
Abnormal number of clonal myeloma cells
Blood and/or urine containing a myeloma protein
Therefore is a significant risk of developing into a malignant
disease
3. Obesity is related to multiple myeloma with each increase of
body mass index
4. Occupational exposure to aromatic
hydrocarbon solvents
• Evidence has shown that these solvents such as
benzene, toluene and xylene have a role in causation
of multiple myeloma.
• The risk of multiple myeloma occurring is greater in
occupations such as;
Firefighter
Hairdresser
Agricultural
Industrial
5. Epstein–Barr virus (EBV)
Rarely, Epstein–Barr virus (EBV) is associated
with multiple myeloma,
When associated with immunocompromised
individuals due to e.g. HIV/AIDS, organ
transplantation, or a chronic inflammatory
condition such as rheumatoid arthritis there is a
high risk of developing multiple myeloma.
SIGNS AND SYMPTOMS
Bone pain, especially in spine or chest
Nausea
Constipation
Loss of appetite
Mental fogginess or confusion
Fatigue
Frequent infections
Weight loss
Weakness or numbness in your legs
Excessive thirst
CLINICAL COMPLICATION
1. Bone complications and pain
Bone pain affects almost 70% of people
with multiple myeloma and is one of the
most common symptoms.
Myeloma bone pain usually involves the
spine and ribs, and worsens with activity.
2. Anemia
The anemia found in myeloma is usually
normocytic and normochromic (normal size and
Hb content respectively but abnormal number of
RBC).
It results from the replacement of normal bone
marrow by infiltrating tumor cells and inhibition
of normal red blood cell production.
3. Impaired kidney function
Impaired kidney function may develop, either acutely or chronically,
and with any degree of severity.
The most common cause of kidney failure in multiple myeloma is due
to proteins secreted by the malignant cells.
Myeloma cells produce monoclonal proteins of varying types, most
commonly immunoglobulins (antibodies) and free light chains,
resulting in abnormally high levels of these proteins in the blood.
Depending on the size of these proteins, they may be excreted
through the kidneys.
Cont…
Kidneys can be damaged by the effects of proteins or light chains
(interfere with absorption process).
Increased bone resorption leads to hypercalcemia and causes
nephrocalcinosis (calcium deposition in renal parenchyma), thereby
contributing to kidney failure.
Amyloidosis (accumulation of abnormal proteins in renal
parenchyma) is a distant third in the causation.
 People with amyloidosis have high levels of amyloid
protein that can be excreted through the kidneys and
cause damage to the kidneys and other organs
4. Infection
Infections are common with multiple myeloma, since the
disease impairs functioning of blood components that
normally resist pathogens.
The most common infections are pneumonias, urinary
tract infections, and sepsis.
The greatest risk period for the occurrence of infection is
in the initial few months after the start of a new MM drugs
therapy.
Many drug therapies further suppress the normal immune
response
5. Neurological impairment
Spinal cord may be affected leading to loss of bowel
or bladder control
6. Mouth
The initial symptoms may involve pain, numbness,
swelling, expansion of the jaw, tooth mobility.
Multiple myeloma in the mouth can cause common
tooth problem
DIAGNOSIS
1. BLOOD TEST
i) Protein electrophoresis of the blood and urine; which might show
the presence of a paraprotein (monoclonal protein, or M protein) band.
There might be a reduction or no change of the other (normal)
immunoglobulins.
One type of paraprotein is the Bence Jones protein, which is a
urinary paraprotein composed of free light chains.
Quantitative measurements of the paraprotein are necessary to
establish a diagnosis and to monitor the disease.
NORMAL SERUM AND URINE PROTEIN
ELECTROPHORESIS
ABNORMAL SERUM AND URINE PROTEIN ELECTROPHORESIS
WITH ADDITIONAL GAMMA MYELOMA PROTEINS
ii) Electrolyte test
Calcium level may be eleveted (when osteoclasts are
breaking down bone, releasing it into the
bloodstream)
iii)Renal function test
Serum creatinine level may elevate due to reduced
kidney function.
2.BONE MARROW BIOPSY
Is usually performed to estimate the percentage
of bone marrow occupied by plasma cells
PREVENTION?

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MULTIPLE MYELOMA.pptx

  • 1. MULTIPLE MYELOMA By Lwitiko Mwakagile Amos Medical Laboratory Scientist Laboratory QMS Mentor
  • 2. MULTIPLE MYELOMA Myel- mean BONE MARROW while –Oma mean TUMOUR Multiple myeloma (MM), also known as plasma cell myeloma, is a cancer of plasma cells, a type of white blood cell that normally produces antibodies. The cause of multiple myeloma is unknown. Risk factors include obesity, radiation exposure, family history, and certain chemicals
  • 3. PATHOPHYSIOLOGY B lymphocytes start in the bone marrow and move to the lymph nodes. As they progress, they mature. When they are activated to secrete antibodies, they are known as plasma cells The immune system keeps the proliferation of B cells and the secretion of antibodies under tight control. When chromosomes and genes are damaged, often through rearrangement, this control is lost. As a result stimulates abnormal antibodies overproduction
  • 4. NORMAL FORMATION OF BLOOD CELLS PATHWAYS
  • 5. ABNORMAL FORMATION OF BLOOD CELLS PATHWAYS
  • 6.
  • 7. CAUSE OF MULTIPLE MYELOMA The cause of multiple myeloma is generally unknown But there is various risk factors that may lead into development of multiple myeloma These risk factors are as follows;
  • 8. 1. Monoclonal gammopathy of undetermined significance (MGUS) Is a plasma cell disease in which plasma cells secrete abnormal antibodies called monoclonal paraproteins or myeloma proteins or M Proteins(gammopathy), into the blood. This abnormal protein is usually found during standard laboratory blood or urine tests. MGUS resembles multiple myeloma and similar diseases
  • 9. Cont…. But the levels of antibodies are lower and the number of plasma cells in the bone marrow is also lower. Rarely has symptoms or major problems MGUS transforms to multiple myeloma at the rate of 1% to 2% per year, and almost all cases of multiple myeloma are preceded by MGUS
  • 10. 2. Smoldering myeloma Is a disease of plasma cells secreting monoclonal paraprotein causes the relatively benign disease of monoclonal gammopathy of undetermined significance. This clone proliferates and may slowly evolve into more aggressive sub-clones that cause smoldering multiple myeloma. Further and more rapid evolution causes the malignant stage of multiple myeloma
  • 11. Cont…. Smoldering myeloma, however, is not a malignant disease. It is characterized as a pre-malignant disease that lacks symptoms Is associated with bone marrow biopsy showing the presence of an Abnormal number of clonal myeloma cells Blood and/or urine containing a myeloma protein Therefore is a significant risk of developing into a malignant disease 3. Obesity is related to multiple myeloma with each increase of body mass index
  • 12. 4. Occupational exposure to aromatic hydrocarbon solvents • Evidence has shown that these solvents such as benzene, toluene and xylene have a role in causation of multiple myeloma. • The risk of multiple myeloma occurring is greater in occupations such as; Firefighter Hairdresser Agricultural Industrial
  • 13. 5. Epstein–Barr virus (EBV) Rarely, Epstein–Barr virus (EBV) is associated with multiple myeloma, When associated with immunocompromised individuals due to e.g. HIV/AIDS, organ transplantation, or a chronic inflammatory condition such as rheumatoid arthritis there is a high risk of developing multiple myeloma.
  • 14. SIGNS AND SYMPTOMS Bone pain, especially in spine or chest Nausea Constipation Loss of appetite Mental fogginess or confusion Fatigue Frequent infections Weight loss Weakness or numbness in your legs Excessive thirst
  • 15. CLINICAL COMPLICATION 1. Bone complications and pain Bone pain affects almost 70% of people with multiple myeloma and is one of the most common symptoms. Myeloma bone pain usually involves the spine and ribs, and worsens with activity.
  • 16. 2. Anemia The anemia found in myeloma is usually normocytic and normochromic (normal size and Hb content respectively but abnormal number of RBC). It results from the replacement of normal bone marrow by infiltrating tumor cells and inhibition of normal red blood cell production.
  • 17. 3. Impaired kidney function Impaired kidney function may develop, either acutely or chronically, and with any degree of severity. The most common cause of kidney failure in multiple myeloma is due to proteins secreted by the malignant cells. Myeloma cells produce monoclonal proteins of varying types, most commonly immunoglobulins (antibodies) and free light chains, resulting in abnormally high levels of these proteins in the blood. Depending on the size of these proteins, they may be excreted through the kidneys.
  • 18. Cont… Kidneys can be damaged by the effects of proteins or light chains (interfere with absorption process). Increased bone resorption leads to hypercalcemia and causes nephrocalcinosis (calcium deposition in renal parenchyma), thereby contributing to kidney failure. Amyloidosis (accumulation of abnormal proteins in renal parenchyma) is a distant third in the causation.  People with amyloidosis have high levels of amyloid protein that can be excreted through the kidneys and cause damage to the kidneys and other organs
  • 19. 4. Infection Infections are common with multiple myeloma, since the disease impairs functioning of blood components that normally resist pathogens. The most common infections are pneumonias, urinary tract infections, and sepsis. The greatest risk period for the occurrence of infection is in the initial few months after the start of a new MM drugs therapy. Many drug therapies further suppress the normal immune response
  • 20. 5. Neurological impairment Spinal cord may be affected leading to loss of bowel or bladder control 6. Mouth The initial symptoms may involve pain, numbness, swelling, expansion of the jaw, tooth mobility. Multiple myeloma in the mouth can cause common tooth problem
  • 21. DIAGNOSIS 1. BLOOD TEST i) Protein electrophoresis of the blood and urine; which might show the presence of a paraprotein (monoclonal protein, or M protein) band. There might be a reduction or no change of the other (normal) immunoglobulins. One type of paraprotein is the Bence Jones protein, which is a urinary paraprotein composed of free light chains. Quantitative measurements of the paraprotein are necessary to establish a diagnosis and to monitor the disease.
  • 22. NORMAL SERUM AND URINE PROTEIN ELECTROPHORESIS
  • 23. ABNORMAL SERUM AND URINE PROTEIN ELECTROPHORESIS WITH ADDITIONAL GAMMA MYELOMA PROTEINS
  • 24. ii) Electrolyte test Calcium level may be eleveted (when osteoclasts are breaking down bone, releasing it into the bloodstream) iii)Renal function test Serum creatinine level may elevate due to reduced kidney function.
  • 25. 2.BONE MARROW BIOPSY Is usually performed to estimate the percentage of bone marrow occupied by plasma cells