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Multiple Myeloma, Amyloidosis, and Other Plasma Cell Disorders

Multiple Myeloma

Multiple myeloma is a blood cancer of the plasma cells and develops in the bone marrow, the soft spongy tissue found in the center of the bones. In addition to plasma cells, bone marrow also contains other blood cells, such as red cells, white cells, and platelets.

Plasma cells in a healthy individual create antibodies that help the body fight off infections and other diseases. In a person with multiple myeloma, the cancerous plasma cells make an abnormal antibody, called a monoclonal protein, or M protein, which can also be called an M-spike, monoclonal immunoglobulin, or paraprotein. The M protein builds up and pushes out the red cells, white cells, and platelets in the bone marrow.

Because there is less room for normal blood cells in the bone marrow, bone damage may occur causing bone pain, osteolytic lesions, which are weak spots on the bones, fractures, or increased levels of calcium in the blood, called hypercalcemia. Decreased blood cell numbers can also cause anemia, excessive bleeding, and a decreased ability to fight off germs or infections. The M protein buildup has the ability to cause kidney damage or damage to other organs if it accumulates too much in the blood or urine. 

Continued research is being done to understand exactly how multiple myeloma forms, but the exact reasoning has not yet been determined. While some mutations have been identified as genetic risk factors, multiple myeloma is not considered a hereditary disease and genetic mutations can vary from person to person.

Multiple myeloma is categorized into three stages, stage I, stage II, or stage III. Stage I is typically less aggressive, while stage III is the most aggressive. Classifying multiple myeloma by stage can lead to a better understanding of the best course of treatment or risk associated with the disease.

Amyloidosis

Amyloidosis is also a disorder of abnormal plasma cells in the bone marrow.

Antibodies are comprised of protein chains, two short light chains and two longer heavy chains. In amyloidosis, the abnormal plasma cells make too many light chains that build up in the tissue and form an abnormal protein, called an amyloid.

An amyloid buildup can cause organs throughout the body to enlarge, affecting the way they work. The heart, kidneys, liver, spleen, nervous system, and digestive tract may all be affected by an amyloid buildup.

There are several types of amyloidosis, some of which are hereditary, and some of which are caused by other factors, such as inflammatory diseases. Each type can impact specific organs or a combination of organs differently.

Light-chain (AL) amyloidosis: affects the kidneys, spleen, heart, and other organs. AL begins in the plasma cells within the bone marrow and create damaged proteins that can gather in other tissues causing damage to vital organs. Individuals with multiple myeloma or other bone marrow illness are more likely to have AL amyloidosis.

AA amyloidosis: most commonly affects the kidneys and is caused by fragments of the amyloid A protein. This form of amyloidosis can complicate inflammatory diseases such as rheumatoid arthritis (RA) or inflammatory bowel disease (IBS).

Transthyretin amyloidosis (ATTR): a type of amyloidosis that can be inherited from a family member. The protein transthyretin is mutates causing amyloid deposits in the liver, impacting that area of the body most prominently.  

Dialysis-related amyloidosis (DRA): this form of amyloidosis is caused by deposits of beta-2 microglobulin that builds up in the bones, joints, or tendons. This type is more common in older adults who have been on dialysis for more than 5 years. 

Other Plasma Cell Disorders

Other plasma cell disorders exist that contain similar characteristics to multiple myeloma and amyloidosis, but don’t meet the same criteria to be classified as them.

Monoclonal gammopathy of undetermined significance (MGUS)

In MGUS, abnormal plasma cells also make copies of the same abnormal antibody, but these cells do not cause the same problems seen in multiple myeloma. While there is still an increase in plasma cells, the cells still only account for less than 10% of the cells in the bone marrow. MGUS is not classified as a cancer, but can be pre-malignant, meaning an individual with MGUS may eventually develop multiple myeloma, lymphoma, or amyloidosis.

MGUS often presents with no symptoms and can be found during a routine blood test where a spike in M protein is observed. Although a patient may remain symptom free for some time, it’s important to continue regular checkups to monitor the M protein levels in the blood. In the event that the disease does progress to myeloma, regular checkups can mean starting treatment earlier and catching the disease at an earlier stage.

Developing symptoms such as bone pain, fatigue, weakness, weight loss, fever, night sweats, headache, dizziness, nerve pain, bleeding, anemia, or swollen lymph nodes may indicate disease progression.

Smoldering multiple myeloma (SMM)

Smoldering multiple myeloma is an early version of myeloma that does not cause an individual any problems or symptoms. Smoldering multiple myeloma contains some of the same signs as multiple myeloma, such as an increased amount of plasma cells in the bone marrow, however, blood counts remain normal and there is no sign of amyloidosis or damage to the bones or organs. SMM can take months to years to become active myeloma and some people never develop active disease.

Solitary plasmacytomas

Solitary plasmacytomas is a disorder classified by a plasmacytoma, or an abnormal plasma cell growth that is cancerous. Unlike multiple myeloma, solitary plasmacytoma only presents with one tumor, rather than multiple tumors in different locations. This disorder often develops in a bone, but can also start in other tissue areas, such as the lungs or other organs. Solitary plasmacytomas also has the ability to turn into multiple myeloma down the road.

Waldenstrom macroglobulinemia (WM)

Waldenstrom macroglobulinemia is a disorder that features a combination of cancer cells similar to multiple myeloma and non-Hodgkin lymphoma. WM cells make high amounts of an antibody known as a macroglobulin, but because each antibody is the same, they are considered M-proteins. The buildup of these antibodies leads to excess bleeding, vision problems, and nervous system problems. While WM is grouped with other plasma cell disorders due to the M-protein buildup, it is also grouped with non-Hodgkin lymphoma due to macroglobulin production.

 

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