Multiple Myeloma

Multiple myeloma is a blood disorder related to lymphoma and leukemia, because it usually arises in the bone marrow. There is no cure for multiple myeloma, but treatments are available that slow its progression.

What Is Multiple Myeloma?

In multiple myeloma, a certain kind of white blood cell called a plasma cell begins to multiply abnormally within the bone marrow. Normally, plasma cells are responsible for producing antibodies that help fight infections. In multiple myeloma, however, excessive plasma cells release unhealthy levels of protein (called immunoglobulin) into the bones and blood. The excessive protein accumulates throughout the body, causing organ damage. 
The plasma cells also cause problems inside bones, where they multiply and crowd out normal blood cells. Inside the bone marrow, multiple myeloma plasma cells release chemicals that prompt the body to dissolve areas of bone. This creates weak areas of bone, which are called lytic lesions.
As multiple myeloma progresses, plasma cells begin to spill out of the bone marrow and deposit elsewhere in the body, causing further organ damage.

Causes of Multiple Myeloma

Multiple myeloma's cause is unknown. Certain risk factors slightly increase a person's chances of developing multiple myeloma. The risk factors are:
  • Being over age 65
  • Being male
  • Being African-American
  • Having a family member affected by multiple myeloma
A significant number of people with certain conditions will develop multiple myeloma. These conditions are:
  • Monoclonal gammopathy of uncertain significance (MGUS)
  • Solitary plasmacytoma
Rather than being causes of multiple myeloma, these conditions may be early forms of multiple myeloma.

Multiple Myeloma Symptoms

Early on, multiple myeloma may cause no symptoms. As multiple myeloma progresses, plasma cells accumulate in the bones, causing these symptoms:
  • Bone pain due to lytic bone disease
  • Weakness and fatigue due to anemia
  • Weight loss
  • Confusion, excessive thirst, constipation due to hypercalcemia
  • Kidney problems
  • Infections due to non-functioning immunoglobulins
Uncommonly, plasma cells may accumulate in purplish lumps visible underneath the skin. These masses are called extramedullary plasmacytomas.

Multiple Myeloma Diagnosis

Most often, testing for multiple myeloma begins after a doctor discovers abnormal blood tests in someone with or without symptoms of multiple myeloma. Some common lab-test clues to the presence of multiple myeloma are:
  • High blood calcium (hypercalcemia)
  • Anemia (low red blood cell count)
  • Elevated creatinine (impaired kidney function)
  • High protein levels in blood, combined with a low albumin level (a "globulin gap")
  • Protein in the urine
When a doctor suspects multiple myeloma, tests of the blood, urine, and bones can make the diagnosis. The most important lab tests of the blood and urine are:
  • Serum protein electrophoresis (SPEP) and immunoelectrophoresis (IFE)
  • Urine protein electrophoresis (UPEP) and urinary immunoelectrophoresis (UFE)
Ninety-seven percent of people with multiple myeloma have an abnormal result on SPEP, UPEP, or both tests. 
An abnormal SPEP (IFE) and/or UPEP (UFE) may lead doctors to recommend a bone marrow biopsy. A bone marrow biopsy is a necessary step in the diagnosis of multiple myeloma. A needle is inserted into a bone, usually in the hip, and a sample of bone marrow is extracted. A diagnosis of multiple myeloma is made when the biopsy reveals an abnormally high number of plasma cells in the bone marrow.
Imaging tests also help doctors make a diagnosis of multiple myeloma and measure its spread. Plain X-ray films of the body's large bones (called a skeletal survey) can identify spots of bone weakened by multiple myeloma. In a few people, a CT scanMRI, or PET scan may be needed to find bone involvement from multiple myeloma. 

Multiple Myeloma Treatment

In general, multiple myeloma treatment primarily helps people who already have signs of organ damage from multiple myeloma. These signs include anemia, high blood calcium, impaired kidney function, or bone lytic lesions.
The initial therapy to treat multiple myeloma is known as induction therapy, using various drugs (described below). In persons under the age of 70, this may be followed by autologous stem cell transplantation (SCT), In SCT, some of a person's stem cells are removed by a machine and are frozen and stored. The stem cells are taken from the person with multiple myeloma, usually after induction therapy. The procedure continues this way:
  • The person with multiple myeloma undergoes high-dose chemotherapy. The strong chemotherapy destroys almost all the cells in the bone marrow -- both healthy cells and the plasma cells causing the disease.
  • The harvested stem cells are then injected into the person's veins. They travel to the bone marrow, where they multiply and make new healthy blood cells.
  • Some people undergo two stem cell transplantation procedures 6 months apart. This is known as tandem stem cell transplantation. Patterns of stem cell transplantation are undergoing clinical trial to determine which pattern is most effective.
  • Allogeneic transplantation is usually reserved for patients with multiple myeloma who have progressed after autologous stem cell transplantation. However, there are clinical trials utilizing tandem autologous stem cell followed by reduced intensity allogeneic stem cell transplantation.
  • After SCT, patients are usually take maintenance therapy for up to 2 years, usually with thalidomide or lenalidomide.
Stem cell transplantation doesn't cure multiple myeloma, but it leads to longer survival. However, SCT can cause serious complications, especially vulnerability to infections.
Chemotherapy refers to drugs that kill cancer cells. Chemotherapy alone is not as effective as stem cell transplantation for multiple myeloma treatment. However, chemotherapy is often a good option for people at higher risk for complications from stem cell transplantation.
To treat multiple myeloma, doctors generally use a combination of chemotherapy and other drugs, which may include:
Doctors can choose from multiple combinations of chemotherapy drugs. Corticosteroids (such as prednisone or dexamethasone) are often given with chemotherapy, to reduce side effects. Interferon is a hormone-like drug that can help keep multiple myeloma in remission after chemotherapy.
Bisphosphonates are drugs used to treat bone damage from multiple myeloma. With multiple myeloma, the bisphophonates primarily used are Aredia (pamidronate) and Zometa (zoledronic acid), which are given intravenously through a vein. A serious side effect of jaw bone death can occur with use of these medications, although it is rare.
Radiation therapy may also help treat multiple myeloma. A beam of radiation is directed from a machine to a bone or other part of the body affected by multiple myeloma. The high-energy rays kill multiple myeloma plasma cells, helping to reduce pain and stabilize the weakened bone. Multiple myeloma cells are highly sensitive to radiation. 
People who aren't candidates for SCT, usually due to age, are given induction therapy followed by chemotherapy.
Multiple myeloma research is ongoing, including clinical trials to identify more effective chemotherapy drugs and combinations.

Multiple Myeloma Survival Rates

Multiple myeloma varies widely between people in its severity and progression. Some people with multiple myeloma will live for years with minimal symptoms. Others have rapid progression of life-threatening multiple myeloma. Identifying the forms of multiple myeloma is often challenging for doctors.
Systems have been developed that attempt to predict a person's survival. The simplest and most common tool uses the blood levels of two substances: albumin and beta-2-microglobulin. A higher albumin level and a lower beta-2-microglobulin level suggest a better chance for prolonged survival.
Other systems use multiple lab tests or tests of the genetics (DNA) in plasma cells to predict survival.
Determining that a person has a more aggressive form of multiple myeloma can help guide treatment and life planning. However, even the best prediction system cannot say how long an individual person will live with the disease. Most people with multiple myeloma will live for years after their diagnosis.

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