Memorial Sloan-Kettering also treats patients with related plasma-cell diseases. These diseases include systemic light-chain amyloidosis (AL), a rare and often fatal disease, and less serious disease conditions, such as solitary plasmacytoma and monoclonal gammopathy of undetermined significance (MGUS).
Select from the list below to learn more about these related blood disorders.
Amyloidosis
Amyloidosis is a group of related diseases in which a complex protein called an amyloid builds up in one or multiple organs, such as the kidney, heart, central nervous system, and/or the liver. As the protein accumulates, it interferes with organ function and eventually causes the affected organs to fail.
Each year, 3,000 cases of amyloidosis are diagnosed in the United States. Symptoms include fatigue and weight loss, and may also include a feeling of fullness if the liver is involved; numbness and tingling in the lower extremities if proteins accumulate in the central nervous system; shortness of breath and dizziness on standing if the heart is affected; and fluid accumulation in the legs if the kidney is affected. Treatment is usually aimed at eliminating the source of the abnormal protein.
There are three major forms of amyloidosis:
The most common form of amyloidosis is called immunoglobulin light-chain, systemic or primary amyloidosis (AL). In patients with this disease, abnormal plasma cells produce a type of protein called an immunoglobulin light-chain protein. The median age at diagnosis is 63.
About one-third of people with AL have a significant amount of protein in their urine (a condition called albuminuria) and have few symptoms of organ involvement. Another third develop protein accumulation in the heart, experience shortness of breath when they exert themselves, and have abnormal findings on a heart study called an echocardiogram. In a quarter of patients with AL, the protein builds up in the liver and gastrointestinal tract, causing stomach discomfort on the right side, abdominal swelling, weight loss, early fullness with eating, and gastrointestinal bleeding. Approximately one-fifth of patients with AL experience peripheral neuropathy, which is degeneration of the nerves in the extremities. This causes sensorimotor symptoms (decreased movement and sensation) that begin in the lower extremities. Other symptoms include light headedness with changes in position, diarrhea or constipation, and erectile dysfunction.
Familial or hereditary amyloidosis (AF) develops among people who inherit a specific genetic abnormality. In the most common type of AF, the liver produces an abnormal form of a protein called transthyretin. Treatment for this form of amyloidosis is liver transplantation.
Secondary amyloidosis (AA), very rare in the developed world, is caused by inflammation resulting from either infectious chronic diseases (tuberculosis, bronchiectasis, osteomyelitis, leprosy) or inflammatory chronic diseases (rheumatoid arthritis, granulomatous ileitis). Treatment involves eliminating the source of inflammation.
To diagnose amyloidosis, physicians use a number of tests, including blood and urine studies, bone marrow studies, and a biopsy taken from an affected organ or a site rich in blood vessels (such as abdominal fat, the gums or gingiva, or the rectum). In over 95 percent of patients with AL, protein (free monoclonal light-chain) is found in the blood.
Treatment
Treatment for AL amyloidosis usually involves combination chemotherapy or stem cell transplantation to eliminate the abnormal plasma cells. For patients who cannot undergo stem cell transplantation, oral therapy with melphalan plus dexamethasone is easily administered and is, in some respects, equivalent to melphalan-based stem cell transplantation. However, oral melphalan involves a risk of stem cell injury and the development of myelodysplastic syndrome (MDS) and secondary leukemia. For those in whom melphalan plus dexamethasone are not effective, doctors may add bortezomib or thalidomide plus dexamethasone.
New Approaches
Our researchers have documented the effectiveness of using thalidomide plus dexamethasone in low doses to treat AL patients after stem cell transplant, if they have not achieved complete responses. In addition, we are testing the use of bortezomib (Velcade®) for AL patients whose disease persists despite treatment and also for patients whose disease relapses after a period of remission.
Memorial Sloan-Kettering investigators have identified a number of unique aspects of amyloidosis, including the role that various genes play in the disease and the frequency with which patients have two different proteins that can cause amyloidosis. We have an active research program seeking to understand why some patients respond so well to stem cell transplantation and others do not. By studying the specific tissues involved — plasma cells, abdominal tissues, and biopsy tissues — we hope to unlock important secrets of this devastating illness over the coming years.
Solitary Plasmacytoma
In rare cases, doctors diagnose a disorder similar to multiple myeloma called solitary plasmacytoma. Patients with this disorder have a localized tumor of plasma cells in the bone, but they have no myeloma cells in their bone marrow and no symptoms of myeloma. For 70 percent of patients with a solitary plasmacytoma, their condition will eventually progress to multiple myeloma. When this type of tumor develops outside the bone — in the lungs, throat, or other organs — it is called an extramedullary plasmacytoma. And 50 percent of those with extramedullary plasmacytoma will develop multiple myeloma.
Monoclonal Gammopathy of Undetermined Significance (MGUS)
Monoclonal gammopathy of undetermined significance (MGUS) is a condition in which patients have moderately elevated levels of a specific protein in the blood. As in multiple myeloma, this protein (called M protein) is produced by plasma cells. In 80 percent of patients with MGUS, however, the protein levels remain constant over time, and symptoms of myeloma do not develop. Some MGUS patients can experience peripheral neuropathy, which is pain or burning sensations in the extremities.
MGUS is more common than myeloma, occurring in 1 percent of Americans over the age of 50 and in 4 percent over age 70. Each year, in 1 to 2 percent of people with MGUS, the condition will progress to a lymphoproliferative disorder (usually multiple myeloma, less often amyloidosis or Waldenström’s macroglobulinemia).
As long as the abnormal protein level does not rise, MGUS requires no treatment. However, patients should have their serum protein levels monitored regularly. Researchers are investigating ways to prevent MGUS from progressing to multiple myeloma, including vaccines, thalidomide, and strategies to block abnormal plasma-cell survival signals.
