Symptoms that May Indicate Multiple Myeloma

Multiple myeloma is plasma cell cancer. Plasma cells , found in the bone marrow, are an essential part of your immune system. Your immune system consists of many kinds of cells. These cells fight against diseases and infections by working together. Lymphocytes are a kind of white blood cells. These lymphocytes include B cells and T cells. The bone marrow, intestines, the bloodstream, and lymph nodes contain lymphocytes.

Plasma cells produce immunoglobulins (antibodies). They aid the body in attacking and killing the germs. The plasma cells are majorly seen in the bone marrow (the soft tissues within the bones). The bone marrow contains platelets, white blood cells, and red blood cells along with the plasma cells.

Multiple myeloma is when the plasma cells become out of control and cancerous. In multiple myeloma , abnormal plasma cells multiply rapidly in the bone marrow. Bone marrow is a soft, blood-producing tissue that fills in the center of most of the bones. As cancer cells do not mature and die as normal cells, they accumulate thus overwhelming the production of healthy cells eventually. Myeloma cells overcrowd the health cells in the bone marrow leading to fatigue and inability to fight the infections.

As healthy plasma cells, myeloma cells also continue trying to produce antibodies. However, myeloma cells produce abnormal antibodies that your body cannot use. In its place, the abnormal antibodies (M proteins or monoclonal proteins) build up in your body and cause problems like damage to the kidneys. Cancer cells can also cause damage to the bones that increases the risk of broken bones.

Causes of myeloma

The exact reason is unknown. Monoclonal gammopathy has been a precursor to multiple myeloma, though not always. Multiple myeloma is not as common as breast, colon, lung, or prostate cancer but is considered the second most common blood cancer after Non-Hodgkin’s lymphoma.

Risk factors of myeloma

1. Age. Increasing age is a risk factor. Older people are more prone. An increase in this condition is seen in people above 60 years of age
2. Gender. Men are more prone when compared to women
3. Race. African Americans show an increased rate of occurrence
4. Genetics. It runs in the family. If one person is affected, others in the family are at a higher risk
5. Environmental causes. A few environmental causes have been identified, but it is not definitive- these factors include radiation exposure, benzene, and insecticides
6. Obesity

Early signs and symptoms:

Early signs and symptoms may or may not be present, but if present, it can include the following :

1. Constipation
2. Nausea
3. Increased thirst
4. Loss of appetite and weight loss
5. Bone pain
6. Confusion
7. Frequent infections
8. Weakness (fatigue)
9. Weakness or numbness in your arms and legs

Characteristic features (definitive signs and symptoms) of multiple myeloma include the following:

a) Low blood count
Due to the malignant cells outnumbering the normal cells, the patients show a significantly low blood count. This can further lead to:

1. Anemia. (shortage in red blood cells) making the patient fatigued and weak.
2. Thrombocytopenia. (due to a decrease in platelet levels) leading to increased bleeding and bruising.
3. Leukopenia. (shortage of normal white blood cells) causes an increased risk of infections.

b) Calcium and bone problems
Bones are consistently remade. This helps keep them strong. The myeloma cells affect the cells that keep the bones strong. There are two types of bone cells that keep the bones strong and healthy by working together.

1. Osteoblasts lay down the new bone.
2. Osteoclasts break down the old bone.
   The myeloma cells produce a substance that indicates osteoclasts to speed up the process of dissolving the bone. Because of this, old bones are broken down without having new bones to replace them. This makes the bones weak and easily breakable. People who suffer from myeloma have a lot of instances of fractured bones. This rise in the bone break down in turn, leads to high blood calcium levels.

c) Hypercalcemia
An increased level of blood calcium is called hypercalcemia. This can cause the following:

1. Bone pain
2. Confusion
3. Drowsiness
4. Nausea
5. Somnolence
6. Constipation
7. Thirst
   If the level gets high enough, the patient may slip into a coma.

d) Nervous system symptoms
Due to bone damage, as explained above, spinal bones and lead to spinal cord compression (where the spinal nerves are pressed when the spinal bones collapse) and causes:

1. Sudden, severe back pain.
2. Numbness, more so in the legs.
3. Muscle weakness, most often in the legs.
   If spinal compression is not treated, it can lead to paralysis.

e) Hyperviscosity
Due to increased monoclonal proteins in the blood, the blood is thick and can slow the blood flow to the brain and cause the following:

1. Dizziness.
2. Confusion.
3. Stroke and slurred speech.
   A process called plasmapheresis can be done to remove the protein from the blood .
   f) Kidney problem
   Myeloma protein can damage the kidneys, as the kidneys bigins to fail, they lose the capacity to remove excess salt, fluid and body waste products, this can lead to the following symptoms:
4. Weakness.
5. Shortness of breath.
6. Itching.
7. Leg swelling.

g) Infection
Multiple myeloma hinder your body’s infection fighting abilities. This can cause increase in the frequency of the infections.

Diagnosis of multiple myeloma
Multiple myeloma is often detected with routine blood tests where the patient presents with low blood count and high total protein level but low albumin levels and high calcium levels. The doctor will conduct a physical examination to detect skin changes such as pallor from anemia, ecchymoses from thrombocytopenia, perform an abdominal, and neurological examination, observe bone tenderness, etc.

Next, bone evaluation is done. For this, a complete radiological skeletal bone scan is necessary to identify possible fractures or areas of disease infiltration. An MRI of the pelvis and spine is done to identify lesions. A whole-body low dose CT scan or PET scan may also be needed to identify other bone lesions.

With this, the doctor will prescribe further tests to detect monoclonal proteins in the blood or 24-hour urine samples by protein electrophoresis. Other tests are then performed, such as immunofixation (to identify the type of monoclonal protein) and tests to measure the levels of the serum-free light chain.

Various blood tests are done, which include the following:
● Complete blood count
● Serum Calcium
● Kidney Function Test (Urea/ Creatinine)
● Total protein, S. Albumin, and S. Globulin
● Beta 2 microglobulin
● S.LDH (lactase dehydrogenase)
● Cytogenetic testing

Complications of myeloma

1. Renal insufficiency. Renal failure is the most common complication associated with myeloma. As high as 25% of patients diagnosed with myeloma need dialysis in the long run.
2. Hematological complications. Since the malignant cells outnumber the normal cells, they cause anemia and bleeding disorders.
3. Increased infections. A decreased number of normal WBCs causes an increased incidence of infections, especially pneumonia, meningitis, influenza, etc.
4. Bone complications. Fractures, spinal compression, and hypercalcemia.

Staging of multiple myeloma
The lower the stage, the better the prognosis. The international system of staging has laid down guidelines based on the serum albumin levels and beta 2 microglobulin levels.

1. Stage 1: Serum beta 2 microglobulin<3.5 mg/dl and serum albumin>/= 3.5 g/dl.
2. Stage 2: Not in stage 1 or 3.
3. Stage 3: Serum beta 2 microglobulin>/= 5.5 mg/l.

Recurrent or relapsed myeloma
Myeloma that comes back after a time of staying under control after the treatment is known as relapsed myeloma or recurrent myeloma. If myeloma reoccurs, cancer will have to be staged once more. This is called re-staging.
Management of myeloma
Treatment should be started as early as possible with the aim to prevent organ damage.

Standard treatment options are as follows:

1. Targeted therapy. Drugs such as Bortezomib, carfilzomib , and ixazomib , block the action of a substance in myeloma cells that break down proteins. This kills the myeloma cells.
2. Biological therapy. Drugs such as thalidomide, lenalidomide, and pomalidomide are prescribed to boost the body’s immune system to identify the malignant cells and kill them.
3. Chemotherapy. Drugs kill fast-growing cells. High doses of chemotherapy drugs are used before the bone marrow transplant.
4. Corticosteroids. Prednisolone and dexamethasone, regulate the immune system to control inflammation in the body.
5. Bone marrow transplant. Also known as stem cell transplant, this is a procedure to replace the diseased bone marrow with healthy bone marrow.
6. Radiation therapy. This is used to kill the myeloma cells and stop their growth.

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Side effects of the treatment
● Loss of Appetite. Try to eat smaller meals and more frequently to combat this issue.
● Constipation. This is generally drug-induced. Laxatives can be used.
● Hair loss.
● Infertility.

Frequently Asked Questions (FAQs)

1. Can myeloma be prevented?
   Since the cause is unknown preventive measures are uncertain.
2. Is multiple myeloma curable?
   At present, there is no permanent cure for myeloma. It can only be managed with stem cell therapy and other measures.
3. What is the life expectancy?
   From the time of diagnosis, a period of 5 to 8 years can be expected based on the severity of the symptoms and the staging of the myeloma.

Read More : Understanding the most common bone marrow cancer: Multiple Myeloma