What is multiple myeloma?
Multiple myeloma is a type of cancer of the plasma cell.
Cancer, to put it in simple terms, is the uncontrolled division of cells.
Lymphocytes are one of the main cells that maintain the body’s immunity. These lymphocytes have B-cells and T-cells which are all part of the body’s defense mechanism. When B cells are activated, they get converted to plasma cells.
Plasma cells are a key component of the white blood cells. They help in producing antibodies. Now, what are antibodies? These are structures that our body makes to kill and defeat foreign bodies, bacterias, and other disease-causing agents.
How does multiple myeloma work?
B-cells from the bone marrow move to the lymph nodes. When they are activated, they become plasma cells. They have various proteins on the cell structure.
In a healthy individual, the immune system controls the proliferation (production) of plasma cells.
Usually, in case of multiple myeloma, there is translocation of the chromosome between the immunoglobulin heavy chain and oncogene.
This results in uncontrolled production of plasma cells which further mutate and lead to more complications.
The plasma cells produce a substance called cytokines, which is increased, causing majority of the localised damage.
The blood vessels and tissues are occluded and blocked by the increased plasma cells leading to further complications.
What are the causes of multiple myeloma?
The cause for multiple myeloma is not established as a pin-point factor but the risk factors may be deciphered.
- CHEMICAL AGENTS: increased exposure to pesticides, herbicides and other chemical effluents have shown to increase the rate of risk of multiple myeloma.
- MONOCLONAL GAMULTIPLE MYELOMAOPATHY OF UNDETERMINED SIGNIFICANCE: a benign proliferation of plasma cells can occur where there is high amounts of monoclonal antibody. This condition is called monoclonal gammopathy of undetermined significance or MGUS. MGUS resembles multiple myeloma but with lower antibody levels. This condition is shown to transform into multiple myeloma at the rate of 1-2%
- SMOULDERING MYELOMA: a type of proliferative disease of plasma cells. It is the pre-malignant stage of multiple myeloma.
- OBESITY: obesity by increase of body mass index by 5 is shown to significantly increase the chances of developing multiple myeloma by 11%.
- AGE: the ages 65 and above are at an increased risk than others.
- RACE: the African-American race is more prone to the disease than the other races.
What are the symptoms associated with multiple myeloma?
- BONE RELATED SYMPTOMS:
- Bone pain: affects almost 70%.
- Pain usually involves the spine and ribs. Spinal chord may get compressed and lead to kyphosis.
- Myeloma genes stimulate a factor called RANKL which further activates osteoclasts which are cells that break down bone structure. This can lead to pathologic fractures and weak bones.
- Also, the calcium from the bones are released into the blood leading to hypercalcaemia.
- Anaemia occurs by replacement of healthy bone marrow with defective bone marrow which leads to reduced red blood cells.
- KIDNEY RELATED SYMPTOMS:
- Multiple myeloma produces increased number of proteins, especially immunoglobulins and free light chains. These get accumulated in the blood and then into the kidneys.
- Bone resorption also leads to excess calcium in the blood which then accumulates in the kidney tubules. This causes a condition called nephrocalcinosis.
- Amyloidosis is a complication of multiple myeloma which is the accumulation of an abnormal protein called amyloid.
- All these stresses to the kidney causes kidney failure.
- Although the number of immunoglobulins are elevated, most are defective and hence non-functional.
- The patient is at a risk for infections especially pneumonia and pyelonephritis.
- The bacterias that cause pneumonia are S. pneumoniae, K. pneumoniae, S. aureus.
- The bacterias that cause pyelonephritis are E. coli and other gram negative bacterias.
- The patient is at maximum risk only during the initial stages.
- NEUROLOGICAL SYMPTOMS:
- Patient may face headaches, retinopathy and visual disturbances.
- This is mainly due to the increased viscosity of blood.
- Patient may also face pain, loss of bowel and bladder control, carpal tunnel syndrome, and other neuropathies.
- This results from spinal cord compression.
What are the tests done to detect multiple myeloma?
- Protein electrophoresis: presence of a paraprotein or M protein, with or without increased levels of immunoglobulin. There may be increased immunoglobulins of all the types although the most common type that’s found is the IgG and IgA.
- Serum calcium and creatinine levels: the serum calcium and creatinine levels are elevated.
- Bone marrow biopsy: shows the defective cells of the bone marrow. Immunohistochemistry is a type of procedure that is done to stain the cells using antibodies on surface proteins.
The defective plasma cells are also seen. They have various altered morphologies like multiple nuclei, cytoplasmic droplets or a distinct fiery red cytoplasm which is called as flame cells.
- Radiographic imaging: X-ray images are taken of various regions, namely skull, spinal cord, and long bones.
The radiographic images show lesions of various types. Sometimes, “lytic lesions” with disappearance of bone structure due to resorption is seen. They may demonstrate “punched-out lesions” which is also known as pepper pot skull. The lesions may also be “sclerotic”.
MRIs and CT scans can also be taken which provide better quality imaging. This can be used to accurately measure the size of the lesions.
There are certain well-defined diagnostic features to differentiate between multiple myeloma and other similar disorders.
Criteria for multiple myeloma: (all three criteria must be met)
- Clonal plasma cells greater than 10% on bone marrow biopsy or in any other biopsy.
- A monoclonal protein in either serum or urine.
- Evidence of an end-organ damage which is related to the plasma cell disorder. This is commonly referred to with the abbreviation “CRAB”
- C: hypercalcaemia
- R: Renal insufficiency
- A: Anaemia
- B: bone lesions like osteoporosis and pathologic fractures.
What are the treatment modalities for multiple myeloma?
Treatment may not be necessary if the patient does not show any symptoms. Instead, constant, periodic monitoring of the patient is required so that the adverse complications can be prevented and managed at the best.
For a patient with symptoms, the staging of multiple myeloma is done. There are certain guidelines for the staging of multiple myeloma, which makes the mode of treatment much easier.
- Targeted therapy: drugs focus on the specific abnormalities within the cancer cell and try to negate the survival capacity of the cancer cells.
Bortezomib, carfilzomib, ixazomib are some drugs which blocks the action of the substance which breaks down proteins. This kills the cells.
They can be taken in pill or intravenous injection.
- Biologic therapy: they are drugs which use the body’s immune system. They enhance the immune system cells which makes them kill the cancer cells. Some of the drugs used are thalidomide, lenalidomide, pomalidomide. These are taken in pill form.
- Chemotherapy: these are drugs that kill the cancer cells which are growing uncontrollably. High doses are given before bone marrow transplant. It may be given intravenously in the arm.
- Corticosteroids: these are drugs which regulate the immune system and control inflammation. Drugs such as prednisolone and dexamethasone are prescribed.
- They are also active against myeloma cells. They can be taken in pill form.
- Bone marrow transplant: it is the treatment which involves replacement of the defective bone marrow with the healthy donor bone marrow. there are two types of bone marrow transplant. AUTO transplants where the bone marrow stem cells are from the person itself. ALLO transplants are stem cells from a compatible donor.
- Radiation therapy: using high intensity radiations, the cancer cells are destroyed and their rapid increase in number is reduced. They are mostly used when the increased cells cause tumours.
Treatment of complications:
- Pain management: pain medications (analgesics)
- Bone pain: if the analgesics fail to relieve the pain, radiation therapy and surgery may also be employed.
- Kidney complications: in severe cases, dialysis may be needed.
- Infections: prophylactic antibiotics may be prescribed; general hygiene of the patient is to be maintained well.
- Bone resorption: bisphosphonate medications like pamidronate, zoledronic acid, may help to prevent or slow down bone resorption.
- Anaemia: medications, and supplements may be recommended by doctors to increase the red blood count.
What is the prognosis of the disease?
Prognosis is a prediction of the outcome of the treatments by considering certain vital factors which are believed to be affecting it.
The prognosis of multiple myeloma mainly depends on the staging. Other factors that affect the prognosis are the age, patient’s body weight, diet and habits.
Cost of treatment:
Indian doctors are medically advanced with years of experience in handling difficult and complex cases of a wide variety. This treatment comes at a lower price than most developed countries in the world while still having advanced technologies and support.
The cost of treatment in India (with respect to stem cell transplant) is around $10800 to $12250.
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