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multiple-myeloma

Multiple Myeloma

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What is Multiple Myeloma ? 

Myeloma is a cancer of the plasma cells in the bone marrow, the spongy tissue inside of bones. Myeloma begins when normal plasma cells change and grow uncontrollably. Plasma cells are a part of the body's immune system and produce antibodies that help the body fight infection. Abnormal plasma cells can suppress the growth of other cells in the bone marrow that produce red blood cells, white blood cells, and platelets. This suppression may result in anemia (from a shortage of red blood cells), excessive bleeding from cuts (from a shortage of platelets), and a decreased ability to fight infection (from a shortage of white blood cells and the body’s inability to respond to infection normally).

Like regular plasma cells, myeloma cells can produce antibodies. However, as the myeloma cells grow uncontrollably, there is overproduction of antibodies, leading to an accumulation in the blood and urine that may cause damage to the kidneys and other organs.

Myeloma often causes structural bone damage resulting in painful fractures (bone breaks). Myeloma is usually called multiple myeloma because most people (90%) have multiple bone lesions at the time it is diagnosed. Solitary plasmacytoma is a mass of myeloma cells that involve only one site in the bone or other organs (most commonly the upper respiratory tract, including the nose and throat). Extramedullary plasmacytoma describes myeloma that started outside of the bone marrow, such as the lymph glands, sinuses, throat, liver, or under the skin.

Risk Factors

A risk factor is anything that increases a person’s chance of developing cancer. Although risk factors often influence the development of cancer, most do not directly cause cancer. Some people with several risk factors never develop cancer, while others with no known risk factors do. However, knowing your risk factors and talking about them with your doctor may help you make more informed lifestyle and health care choices.

The causes of myeloma are not known or well understood, and there are currently no known ways to prevent it. There are also no strong risk factors for myeloma. Mutations in plasma cells are acquired, not inherited, so having a relative with the disease usually does not mean another family member is at higher risk for developing it. There appears to be a very slight increase in the incidence of the disease in first-degree relatives (parents or siblings) of people with multiple myeloma, but this link is not yet shown to be genetic.

The following factors can raise a person's risk of developing myeloma:

Age. Myeloma occurs most commonly in people over 60. The average age at diagnosis is 70. Only 2% of cases occur in people under 40.

Race. Myeloma occurs twice as frequently in black people than in white people for unclear reasons.

Exposure to radiation and chemicals. People who have been exposed to radiation or to asbestos, benzene, pesticides, and other chemicals used in rubber manufacturing may be at higher risk for developing myeloma.

Personal history. People with a history of a solitary plasmacytoma are at greater risk for developing multiple myeloma.

Monoclonal gammopathy of unknown significance (MGUS). A person with a low level of a certain antibody protein in his or her blood, called the M protein, have a 1% chance of developing myeloma or another blood-related cancer called lymphoma per year.

Gender. Myeloma is slightly more common in men.

Symptoms and Signs : People with multiple myeloma may experience the following symptoms and signs. Sometimes, people with multiple myeloma do not show any of these symptoms. For people with myeloma who have no symptoms, their cancer may be discovered by a blood test performed for some other reason, such as at an annual physical. Or, these symptoms may be caused by a medical condition that is not cancer. If you are concerned about a symptom or sign on this list, please talk with your doctor.

Anemia is a low level of red blood cells, which happens when the myeloma plasma cells crowd out normal red blood cells.

Fatigue is usually caused by anemia and occurs in most people with myeloma.

Bone pain, a common symptom, is caused by local bone damage and osteoporosis (general thinning of the bone), which makes the bone more likely to break. The back or ribs are the most common sites of bone pain, but any bone can be affected. Pain is usually worse with movement and at night. If cancer is in the spine, the vertebrae (individual bones that make up the spine) can collapse and cause nerve pain. In advanced multiple myeloma, a patient may lose inches from his or her height due to compressed vertebrae.

Kidney damage or failure

Weight loss, nausea, thirst, muscle weakness, and mental confusion symptoms are related to kidney failure, hypercalcemia (high calcium levels in the blood), or other imbalances in blood chemicals.

Hypercalcemia, resulting in symptoms of drowsiness, constipation, and kidney damage

Infections, especially of the upper respiratory tract and lungs

Blood clots, nosebleeds, bleeding gums, bruising, and hazy vision caused by hyperviscosity (thickened blood)

Your doctor will ask you questions about the symptoms you are experiencing, if any, to help find out the cause of the problem, called adiagnosis. This may include how long you’ve been experiencing the symptom(s) and how often.

If cancer is diagnosed, relieving symptoms and side effects remains an important part of cancer care and treatment. This may also be called symptom management, palliative care, or supportive care. Be sure to talk with your health care team about symptoms you experience, including any new symptoms or a change in symptoms.

Diagnosis :  Doctors use many tests to diagnose cancer and find out if it has metastasized (spread). Some tests may also determine which treatments may be the most effective. For most types of cancer, a biopsy (the removal of a small amount of tissue for examination under a microscope) is the only way to make a definitive diagnosis of cancer. If a biopsy is not possible, the doctor may suggest other tests that will help make a diagnosis. Imaging tests may be used to find out whether the cancer has metastasized. Your doctor may consider these factors when choosing a diagnostic test:

Age and medical condition

Type of cancer suspected

Severity of symptoms

Previous test results

In addition to a physical examination and biopsy, the following tests may be used to diagnose multiple myeloma:

Blood and urine tests. Myeloma cells secrete an antibody known as the M protein (monoclonal immunoglobulin). Levels of the M protein in a patient's blood and urine are used to determine the extent of the disease and to monitor the effectiveness of treatment. The levels of serum albumin (a blood protein made by the liver that is necessary for maintaining proper blood volume) and serum beta 2-microglobulin (β2-M, a small protein that plays a role in immunologic defense) are measured using blood tests; these results are important for staging. Blood tests are also used to measure kidney function, calcium levels, and blood counts (for possible anemia).

X-ray. An x-ray is a way to create a picture of the structures inside of your body using a small amount of radiation. X-rays are typically the first step in evaluating bones when myeloma is suspected or diagnosed.

Bone marrow biopsy and aspiration. These two procedures are similar and often done at the same time. Bone marrow has both a solid and a liquid part. A bone marrow biopsy is the removal of a small amount of solid tissue using a needle, and it is important to making a diagnosis of myeloma. An aspiration removes a sample of fluid with a needle. The sample(s) are then analyzed by a pathologist, a doctor who specializes in interpreting laboratory tests and evaluating cells, tissues, and organs to diagnose disease. A common site for a bone marrow biopsy and aspiration is the pelvic bone, which is located in the lower back by the hip. The skin in that area is usually numbed with medication beforehand, and other types of anesthesia (medication to block the awareness of pain) may be used. 

Fat pad aspirate. If M proteins are deposited in body tissues, it can cause organ dysfunction. This condition is called amyloidosis. If amyloidosis is a consideration, it may be necessary to take a sample of the abdominal fat pad (the collection of fat around a person's abdomen) for examination under a microscope, called a biopsy.

Molecular testing of the tumor. Your doctor may recommend running laboratory tests on a tumor sample to identify specific genes, proteins, and other factors unique to the tumor. Results of these tests may help guide your treatment options .

Magnetic resonance imaging (MRI). An MRI uses magnetic fields, not x-rays, to produce detailed images of the body. An MRI can show replacement of normal bone marrow by myeloma cells or plasmacytoma (a plasma cell tumor growing in bone or soft tissue), especially in the skull, spine, and pelvis. The detailed images may also show compression fractures of the spine or a tumor pressing on nerve roots. A contrast medium (a special dye) may be injected into a patient’s vein to create a clearer picture.

Computed tomography (CT or CAT) scan. A CT scan creates a detailed, cross-sectional view that shows any abnormalities or tumors in soft tissues. A computer then combines these images into a three-dimensional picture of the inside of the body. Sometimes, a contrast medium is injected into a patient’s vein to provide better detail, but it is used cautiously in patients with multiple myeloma because of a risk of kidney failure.

Positron emission tomography (PET) scan. A PET scan is a way to create pictures of organs and tissues inside the body. A small amount of a radioactive substance is injected into a patient’s body. This substance is absorbed mainly by organs and tissues that produce the most energy. Because cancer tends to use energy actively, it absorbs more of the radioactive substance. A scanner then detects this substance to produce images of the inside of the body.

Integrated PET-CT scan. An integrated PET-CT scan combines the images from a positron emission tomography (PET) scan and a computed tomography (CT) scan, performed at the same time on the same machine. Together, the two scans create a more complete image than either test can offer alone.

Stages : Staging is a way of describing where a cancer is located, if or where it has spread, and whether it is affecting the functions of other organs in the body. Doctors use diagnostic tests to determine the cancer's stage, so staging may not be complete until all of the tests are finished. Knowing the stage helps the doctor to decide what kind of treatment is best and can help predict a patient's prognosis (chance of recovery). There are different stage descriptions for different types of cancer.

In myeloma, it is important to begin with whether the patient is experiencing symptoms. It is common to classify patients with newly diagnosed myeloma as being either symptomatic from the disease (having symptoms and signs) or asymptomatic (without any symptoms). Patients without symptoms are generally watched closely without treatment, which is called active surveillance .  Patients with symptoms need treatment.

As described below, the symptoms related to the myeloma include hypercalcemia (elevated blood Calcium), poor Renal or kidney function, Anemia, or Bone pain or bone lesions (CRAB).

Calcium levels increased: serum calcium > 0.25 mmol/l above the upper limit of normal or > 2.75 mmol/l

Renal insufficiency: creatinine > 173 mmol/l

Anemia hemoglobin 2 g/dl below the lower limit of normal or hemoglobin < 10 g/dl

Bone lesions; lytic lesions or osteoporosis (thinning of the bones) with compression fractures (an MRI or CT test may clarify)

Other: symptomatic hyperviscosity, amyloidosis, and/or recurrent bacterial infections (more than 2 episodes in 12 months)

The Durie-Salmon system had traditionally been used for the staging of myeloma. This staging system is good for assessing the extent of the disease or size of the tumor. According to this system there are three stages; each stage is further subclassified into A or B depending on whether kidney function has been affected (with the subclassification B meaning there is significant kidney damage).

However, another classification system called the International Staging System (ISS) is now used more commonly. It defines the factors that influence patient survival. The ISS is based on data collected from patients with multiple myeloma from around the world. The system has three stages based on the measurement of serum albumin and the levels of serum β2-M. Recent efforts involve further classifying myeloma based upon patterns of gene expression in myeloma cells; this is an ongoing area of research.

Stage I :  Many patients with stage I myeloma show no symptoms because there are fewer cancer cells in the body. If the cancer has affected kidney function, the prognosis may be worse regardless of the stage. Factors characteristic of stage I include:

Durie-Salmon system 

Number of red blood cells within or slightly below normal range

Normal amount of calcium in the blood

Low levels of M protein in the blood or urine

No bone damage on x-rays

ISS

β2-M less than 3.5 grams per deciliter (gm/dL)

Albumin greater than or equal to 3.5 gm/dL

Stage II

Durie-Salmon system : More cancer cells are present in the body in stage II. Again, if kidney function is affected, then the prognosis worsens regardless of the stage. Criteria for stage II are defined as those that fit neither stage I nor stage III.

ISS

β2-M greater than 3.5 gm/dL, but not greater than 5.5 mg/dL, and/or

Albumin less than 3.5 gm/dL.

Stage III : Many cancer cells are present in the body at stage III. Factors characteristic of this stage are:

Durie-Salmon system

Anemia with a hemoglobin less than 8.5 gm/dL

Hypercalcemia

Advanced bone damage (more than three bone lesions)

High levels of M protein in the blood or urine, which is defined as:

Immunoglobulin G (IgG; an antibody in the blood that fights infection) value greater than 7 gm/dL

IgA (Immunoglobulin A; another specific type of antibody) value greater than 5 gm/dL

Urine light chain M component on electrophoresis greater than 12gm/24h. This is a type of protein that is usually cleared from the blood through the kidneys and then reabsorbed. If this is found in the urine, it could indicated multiple myeloma, and electrophoresis is the method that laboratory uses to identify and classify it.

ISS

β2-M greater than 5.5 gm/dL

Recurrent myeloma: Myeloma that returns after a period of being in control after treatment is called recurrent myeloma or relapsed myeloma. If there is a recurrence, the cancer may need to be staged again (called re-staging) using the system above.

Other classifications : Some people have no symptoms of myeloma, but they may have abnormal plasma cells producing an abnormal protein (M protein). Doctors generally monitor these people closely, and active treatment does not begin unless this condition turns into symptomatic myeloma.

Monoclonal gammopathy of unknown significance (MGUS) : This condition occurs when people have a low level of M protein (meaning there are small quantities of abnormal plasma cells), but they do not have any other evidence of myeloma, such as bone damage, excessive plasma cells, or low numbers of red blood cells. People with MGUS have a 1% chance per year of developing myeloma or lymphoma. For this reason, doctors monitor the health of people with MGUS on a regular basis.

Smoldering multiple myeloma (SMM) or asymptomatic myeloma :  People who are diagnosed with SMM have slightly higher levels of M protein and more plasma cells in the bone marrow than people with MGUS. There is still no evidence of symptoms or signs of myeloma, such as bone disease or anemia. But, a person with SMM may be prescribed bisphosphonates for symptoms of osteoporosis or osteopenia (a low density of bone minerals). Most people with SMM eventually develop myeloma. For this reason, doctors closely monitor the health of people with smoldering myeloma.

Prognosis : The International Staging System (ISS) of myeloma gives information about prognosis and predicts the person’s chance of recovery. Researchers are also looking at other ways to predict prognosis for patients with multiple myeloma. Some of these ways of evaluating prognosis include:

High levels of β2-M may indicate a large number of myeloma cells are present and kidney damage has occurred. The level of this protein increases as myeloma becomes more advanced.

Lower amounts of serum albumin may indicate a poorer prognosis.

Lactase dehydrogenase (LDH) is an enzyme; higher blood levels of LDH indicate a poorer prognosis.

Abnormalities of chromosomes in the cancer cells may show how aggressive the cancer is.

A plasma cell labeling index can be done in a specialized laboratory using bone marrow samples to find out how fast the cancer cells are growing.

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