Multiple myeloma (MM) is a cancer of the plasma cells, a type of white blood cell. Plasma cells are an important part of the immune system because they produce antibodies called immunoglobulins that help the body fight infection.
MM begins in the bone marrow—the soft, spongy tissue that fills the center of bones. The bone marrow is where blood cells such as red blood cells, white blood cells, and platelets are made. Patients with MM develop a large number of abnormal plasma cells in their bone marrow. The cancerous plasma cells multiply, building up in the marrow and crowding out normal, healthy blood cells.
This buildup of myeloma cells can lead to medical problems and complications:
- A reduction in blood cell production
- Damage to nearby bones
- Organ damage
- Problems with blood clotting and circulation
There is currently no cure for the majority of MM patients, but it is a treatable disease.
There are different forms of myeloma-related conditions. Some require treatment and some do not. All myeloma conditions require regular check-ups to monitor whether the disease is progressing.
- Monoclonal gammopathy of undetermined significance (MGUS)
People who have MGUS have a small number of myeloma cells in the bone marrow, but these cells are not forming a tumor and symptoms of myeloma are not present. This condition is usually discovered during a routine blood exam that shows unusual levels of protein in the blood.
- MGUS is a pre-cancerous condition. Therefore, check-ups should occur every 6 months to monitor the condition and make sure that it does not develop into MM. MGUS develops into MM in only a small number of patients.
- A diagnosis of MGUS should not be made without a chromosome analysis, gene array, MRI, and/or a PET/CT scan.
- Asymptomatic (Smoldering/Indolent) Myeloma
Asymptomatic myeloma falls somewhere between MGUS and symptomatic multiple myeloma. In this condition, a person has a greater number of myeloma cells than a person with MGUS. However, the disease does not cause any damage to the body and the typical myeloma symptoms are not present, though patients may exhibit anemia due to causes other than myeloma.
- Asymptomatic myeloma can be stable for many months or years, but it ultimately tends to progress. The patient will likely need treatment at some point. He or she will need to be monitored to see if the disease progresses and if symptoms appear.
- Symptomatic (Active) Myeloma
This type of myeloma represents overt cancer. A person with symptomatic myeloma has more myeloma cells than a person with asymptomatic myeloma or MGUS.
- At this point, the disease is causing the body damage, such as bone damage, anemia, kidney problems, or hypercalcemia (high levels of calcium in the blood).
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Several factors influence the risk of developing multiple myeloma:
- Age: Growing older increases the chance of developing multiple myeloma. Most people with myeloma are diagnosed after age 65. This disease is rare in people younger than 35.
- Being male: More men are diagnosed with multiple myeloma each year than women. It is not known why.
- Family history of multiple myeloma: Studies have found that a person's risk of multiple myeloma may be higher if a close relative had the disease.
- Personal history of monoclonal gammopathy of undetermined significance (MGUS): MGUS is a benign (non-cancerous) condition in which abnormal plasma cells make M proteins. Some people with MGUS develop multiple myeloma. People with MGUS get regular lab tests and physical exams to watch for any signs of disease development.
- Race: The risk of multiple myeloma is highest among African Americans and lowest among Asian Americans. The reason for this is not known.
Researchers continue to study other risk factors such as being exposed to certain chemicals or viruses, having alterations in certain genes, eating certain foods, or being obese.
Common symptoms of multiple myeloma include the following:
- Bone pain, usually in the back and ribs
- Broken bones, usually in the spine
- Feeling very thirsty
- Feeling weak and very tired
- Frequent infections and fevers
- Frequent urination
- Nausea or constipation
- Weight loss
Other health problems can also cause these symptoms. People with these symptoms should see their doctor.
There is no routine test to screen for multiple myeloma. Myeloma is usually detected in patients that go to the doctor because of other health problems. Doctors often detect it after a blood test or suspect it after an x-ray of a broken bone.
To diagnose multiple myeloma, a doctor may order some of the following tests:
- Blood tests: Doctors check for specific substances in the blood that indicate myeloma, such as levels of certain proteins, calcium, and creatinine.
- Urine tests: The lab checks for Bence Jones protein, a type of M protein in urine, which is then collected over a 24-hour period. If the lab finds a high level of Bence Jones protein in the urine sample, doctors will monitor the kidneys. Bence Jones protein can clog the kidneys and damage them.
- X-rays: The patient may have x-rays to check for broken or thinning bones. An x-ray of the whole body can be done to see how many bones could be damaged by the myeloma.
- Biopsy: The doctor removes tissue to look for cancer cells. A biopsy is the only sure way to know whether myeloma cells are in the bone marrow. There are two ways a doctor can obtain a bone marrow sample. Some people will have both procedures during the same visit:
- Bone marrow aspiration: The doctor uses a thick, hollow needle to remove samples of bone marrow.
- Bone marrow biopsy: The doctor uses a thick, hollow needle to remove a small piece of bone and bone marrow.
To be diagnosed with MM, a person must have one major condition and one minor condition, or they must have three minor conditions.
- Confirmed plasmacytoma (solid tumor of plasma cells)
- Bone marrow sample in which 30% or more cells are plasma cells
- High levels of monoclonal protein (M-protein) in the blood or urine
- Bone marrow sample in which 10-29% cells are plasma cells
- Smaller levels of M-protein levels in blood or urine
- Holes in bones from myeloma growth
- Abnormally low levels of antibodies in the blood
If the biopsy shows myeloma cells, it is important to know the stage (extent) of the disease to plan the best treatment. Staging may involve having more tests:
- Blood tests: The doctor tests for levels of specific substances in the blood, including albumin and beta-2-microglobulin.
- CT scan: Doctors often use CT scans to take pictures of tissue inside the body. An x-ray machine linked to a computer takes several pictures. The pictures may show whether cancer has spread to lymph nodes or other areas in the body.
- Magnetic resonance imaging (MRI): This procedure uses a magnet, radio waves, and a computer to make a series of detailed pictures of areas inside the body.
Stages of Multiple Myeloma
Staging is the process of finding out the extent of a person's myeloma. There are two staging systems that myeloma doctors consult:
- Durie-Salmon staging
In this system, there are three stages of myeloma: Stage I, Stage II, and Stage III. The stage depends on certain factors:
- The amount of myeloma cells in the body
- The amount of damage the myeloma cells have caused to the bone
- Levels of M-protein in the blood or urine
- Blood calcium levels
- Albumin and hemoglobin levels
- Myeloma can also be further classified into Group A or Group B, based on damage to the kidneys. Group A indicates normal kidney function. Group B indicates abnormal kidney function. A person could be classified as Stage IIB, for example.
- International Staging System (ISS)
This staging system is based on the albumin level (more or less than 3.5 mg/dL) and B2-microglobulin level (< 3.5; 3.5-5 or > 5 mg/L). The lower the stage, the better the outcome. This staging system is based on outcomes of more than 10,000 cancer cases.
At Huntsman Cancer Institute (HCI), multiple myeloma is treated by a team of specialists, including hematologic oncologists (doctors who specialize in cancers of the blood), medical oncologists, nurses, dietitians, social workers, and other professionals.
Treatment options for multiple myeloma include medications, autologous stem cell transplant, and allogeneic stem cell transplant.
Proteasome inhibitors. Proteasomes are enzymes found in cells. They help control cell function and growth by controlling the breakdown of important proteins. Proteasome inhibitors blocks the activity of proteasomes. This disrupts the growth and survival of cancer cells, especially myeloma cells.
Immunomodulatory drugs (IMIDs) is a cancer drug used to treat multiple myeloma. It is taken by mouth. IMIDs work against cancer cells by affecting the immune system. IMIDs works to slow or kill myeloma cells. It directly affects the tumor cells. It also affects the blood vessels and other substances surrounding a tumor that help feed the cancer cell's growth.
Autologous Stem Cell Transplant
Autologous stem cell transplant is a procedure where a patient's own healthy bone marrow stem cells are collected before high-dose chemotherapy and then given back after the treatment. This way, the healthy stem cells are not damaged by the high-dose chemotherapy.
After chemotherapy, patients go through a period where they are more likely to get infections and bleeding. Giving a patient back his or her unharmed stem cells significantly reduces the length of this period to about one week. The stem cells help the body rebuild the blood and immune system more quickly. Without the transplant, it would take six to eight weeks for the person's blood counts to return to normal levels.
Most autologous transplants can be done safely on an outpatient basis with careful monitoring. Learn more in our video about HCI's Blood and Marrow Transplant program.
What are the steps in an autologous stem cell transplant?
- The first step is to collect the bone marrow stem cells. In the past, this was done by going into the bone marrow to get the stem cells. Today we use a method called mobilization. With mobilization, the patient receives some chemotherapy combined with growth factors. This tricks the stem cells into leaving the bone marrow and going into the peripheral blood, where they can be collected more easily.
- The stem cells are collected using an intravenous line, or central line, that is inserted into the chest. Blood is withdrawn and circulated through an apheresis machine, which is a device that separates white blood cells from the rest of the blood. The white blood cells contain the stem cells.
- White blood cells make up less than 1% of our blood. When the white cells are collected, the rest of the blood (the other 99%) is returned to the patient through the machine. The stem cells are frozen until it is time to give them back to the patient.
- Next, the patient receives chemotherapy to fight the myeloma. The chemotherapy contains anti-cancer drugs. These chemotherapy drugs will have certain side effects, so the patient may get other medications to fight the side effects.
- The next step is to give back some of the healthy stem to the patient. Some of the cells are thawed and given back, or infused, through the central line in the chest. The rest of the stem cells will stay frozen and be stored for use during the second transplant. When the stem cells are infused, they move from the blood back to the bone marrow.
- The infused cells now have the important job of rebuilding the blood and immune system. The patient is monitored to see if engraftment occurs. Engraftment is when the body starts to reproduce the white blood cells and platelets and can once again fight infection. Engraftment usually occurs 12 to 15 days after the stem cells have been given back.
We ask patients to stay in the Salt Lake City area for about three weeks during their transplant. The transplant is usually done on an outpatient basis, and patients don't need to spend the night at the hospital. However, patients will need to return to the hospital frequently for monitoring.
Tandem Autologous Transplant
A tandem autologous transplant means that two autologous transplants are done within six months. This is also known as a double autologous transplant. Studies have shown improved response and survival rates with tandem transplants compared to a single transplant. Patients usually live longer and have a better quality of life. Learn more in our video about HCI's Blood and Marrow Transplant program.
The period of time between the first transplant and second transplant is about two and a half to three months. Data show that with autologous transplants, half of myeloma patients will survive more than ten years after the start of treatment. For myeloma patients who receive conventional chemotherapy, the median survival rate is two and a half to three years, with only five percent of patients living ten years or more.
Allogeneic Stem Cell Transplant
An allogeneic stem cell transplant is a procedure where the stem cells are taken from another individual who is genetically similar or matched to the patient. The donor's cells must match the patient's, just as with a kidney or other organ transplantation.
In many cases, the stem cell donor is related to the recipient, typically a brother or sister. Stem cells from unrelated donors can also be used if there is a match. It may also be possible to use cells from banked cord blood.
High-dose chemotherapy followed by an allogeneic transplant has the potential to possibly provide better long-term control of myeloma (with longer time without disease progression) than autologous transplants. However, it is a risky procedure with a high death rate of 20% to 50% from the procedure itself. As a result, this type of transplant is rarely performed.
A safer type of allogeneic transplant is much more common. This type of transplant is called a mini-allogeneic transplant. It is also called a reduced intensity or non-myeloablative allogeneic transplant. A mini-transplant uses lower doses of chemotherapy prior to transplant. As a result, the rate of death due to the procedure is very low, similar to that of an autologous transplant.
These studies discover and evaluate new and improved cancer treatments. Patients are encouraged to talk with their doctors about participating in a clinical trial or any questions regarding research studies. For more information, also visit HCI's clinical trials website.
When you or someone you love is diagnosed with cancer, concerns about treatments and managing side effects, hospital stays, and medical bills are common. You may also worry about caring for your family, employment, or how to continue normal daily activities.
Here's where you can go for support:
- Your health care team can answer your questions and talk to you about your concerns. They can help you with any side effects and keep you informed of all your treatments, test results, and future doctor visits.
- Our Patient and Family Support Services professionals offer HCI patients and their families emotional support and resources for coping with cancer and its impact on daily life.
- The Linda B. and Robert B. Wiggins Wellness-Survivorship Center offers support groups, classes, and activities aimed to increase the quality of life and well-being of HCI patients and their families.
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Did You Know?
- Multiple myeloma can also be referred to as Kahler disease, myelomatosis, and plasma cell myeloma.
- An estimated 20,520 new cases of multiple myeloma will be diagnosed in the United States this year.
The sources for this information are the National Cancer Institute and specialists at Huntsman Cancer Institute.