Myeloma

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The blood contains several different types of cells, each with an important job in the body. All blood cells develop in the bone marrow, the spongy substance within our bones. The originator of all blood cells is an immature cell known as the stem cell. The stem cells give rise to committed or programmed stem cells, which then differentiate to form mature cells that circulate in our blood. There are 3 basic blood cell types:

• Red blood cells carry oxygen to, and carbon dioxide from, all bodily tissues in order to maintain effective organ function.
• Platelets, in combination with certain plasma proteins, help produce blood clots, which prevent bleeding.
• White blood cells are part of the immune system, which protects the body from pathogens (things that can make us ill) such as infectious agents and precancerous cells. One of the most important subtypes of white blood cells is the lymphocyte. There are 2 major subtypes of lymphocytes: B lymphocytes and T lymphocytes (often called B cells and T cells). Some B lymphocytes mature into plasma cells. Plasma cells serve as producers of important protective proteins, called antibodies, which circulate and bind to various pathogens, rendering them harmless and susceptible to removal by other white cell components.

Myeloma is an accumulation of malfunctioning or "cancerous" plasma cells. Cancer is a disorder characterized by transformation of normal cells to abnormal cells that grow and multiply uncontrollably. The net effect is the appearance of large numbers of abnormal cells capable of forming bodily masses, or tumors, with the capacity to advance locally and invade adjacent tissues and organs or spread either through the lymphatics or the blood vessels into distant organs. The ultimate effect of this "malignant" upheaval is erosion and organ dysfunction.

• Most plasma cells reside in the bone marrow, and myeloma, accordingly, usually occurs within the marrow-containing large bones of the body, such as the skull, vertebrae (spine), and hips.
• Because they are present throughout the bone marrow, plasma cells that have undergone malignant transformation do so in clumps and usually at many sites, which explains the terminology "multiple myeloma." When only one site is detectable, it is referred to as a solitary plasmacytoma, and these respond dramatically to local radiation or surgical excision. However, the recurrence rate is high, and they may recur years later as solitary or multiple tumors.

Because plasma cells are part of the immune system and produce antibodies, the development of myeloma results in an impaired immune system with problems associated with antibody overproduction, as well as the problems associated with any invasive tumor.

• Normal plasma cells produce antibodies, also called immunoglobulins (Ig). The abnormal plasma cells in myeloma do not produce the normal vast array of different immunoglobulins. Instead, myeloma cells may produce an abnormal immunoglobulin called a monoclonal protein, or M protein. (Monoclonal means that all proteins produced by this cell line have exactly the same identity and the same impaired function, which is essentially a deficiency.) Accordingly, most patients with myeloma have difficulty fighting off infections.
• Plasma cell tumors in the bone marrow crowd out the normal components of the marrow, resulting thereby in decreased numbers of red blood cells, platelets, and other white blood cells. This problem then results in fatigue and shortness of breath (decreased red cell count), bleeding or easy bruising (low platelet count), and increased susceptibility to infections (low white blood cell count).
• In myeloma, the abnormal plasma cells eventually invade and destroy the outer, hard layer of bone. The destruction of bones (osteolysis), typically occurring in small areas at different sites, may lead to serious problems. Even a small osteolytic lesion can cause the bone to fracture and collapse. The net effect may be problems with mobility, severe pain, and in the presence of spinal involvement, moderate-to-severe nerve damage.
• Boney destruction is often associated with high levels of blood calcium (hypercalcemia.)
• Production of M protein by the abnormal plasma cells causes high protein levels in the blood. The extra protein can lodge in the kidneys and obstruct blood flow. The abnormal protein can be directly toxic to the cells in the kidneys as well. The kidneys may become functionally impaired and ultimately fail altogether as a result of the protein blockage.
• In some cases of myeloma, excess protein in the blood can cause a condition called hyperviscosity syndrome. The type and amount of immunoglobulin protein can result in thickening the blood beyond normal blood viscosity, which may result in alteration in a variety of bodily, including mental, processes. This syndrome accounts for fewer than 5% of people with myeloma.
• Not everyone with myeloma has bone or kidney involvement at the time of diagnosis, but if the disease progresses without treatment, these problems may ultimately arise.

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