Myeloma Overview

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.Theoriginator of all blood cells is an immature cell known as the stem cell.The stem cells give rise tocommitted or programmedstem cells, which then differentiate to form mature cellsthat circulate in our blood. There are 3 basic blood cell types:

  • Red blood cells carry oxygen to, and carbon dioxide from, allbodily tissues in order to maintain effective organ function.
  • Platelets, in combination with certain plasma proteins,help produceblood clots, whichprevent bleeding.
  • White blood cells are part of the immune system, which protects the body from pathogens (thingsthat can make us ill) such as infectious agents and precancerouscells. 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. Canceris a disorder characterized by transformation ofnormal cells toabnormal cells that grow and multiply uncontrollably. The net effect is the appearance of large numbers of abnormal cellscapable of forming bodilymasses, or tumors, with the capacityto 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 iserosion 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 skullvertebrae (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 recuryears 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 withany invasive tumor.

  • Normal plasma cells produce antibodies, also called immunoglobulins (Ig).The abnormal plasma cells in myelomado not produce the normal vast array of different immunoglobulins.Instead, myeloma cells may produce an abnormal immunoglobulincalled 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, hardlayer 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 nervedamage.
  • Boney destruction is often associated with high levels of blood calcium(hypercalcemia.)
  • Production of M proteinby 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 forfewer 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.

Other complications of myeloma may include the following:

  • Cryoglobulinemia: People with thisrare condition produce a protein that precipitates, or falls out of solution, when the blood is exposed to cold temperatures.
  • Amyloidosis: This rare complication occurs mostly in people whose myeloma produces the light chain components of immunoglobulins. The light chains combine with other substances in the blood to form a sticky protein called amyloid, which impairs the function of whichever organ in which it may accumulate.

Different types of myeloma are classified by the type of immunoglobulin produced by the abnormal plasma cells. Immunoglobulins (Ig) are made up of 2 components: light chains and heavy chains andfurther classified by the type of light(kappa or lambda) or heavy(alpha [IgA], gamma [IgG], mu [IgM], delta [IgD], and epsilon [IgE]) chains.

  • The most common monoclonal protein in myeloma is the IgG type.This means that the immunoglobulin is comprised of 2 IgG heavy chains and 2 light chains, either 2 kappa or 2 lambda.When the abnormal M protein is identified in myeloma, it is most often an IgG kappa type. However, any other combination is possible.
  • Less common, but still prevalent, are IgA-producing myeloma cells.
  • IgM myeloma is much less common.
  • IgD and IgE myelomas are very rare.
  • Some myelomas produce an incomplete immunoglobulin consisting of light chains only, known as Bence-Jones proteins, which are not identified by blood tests but readily identified in urine.
  • Some rare diseases are associated with plasma cell overproduction of heavy chains only. These are referred to as heavy chain diseases.Heavy chain diseases may or may not be similar to myeloma in their characteristics.
  • Nonsecretory myeloma occurs in about 1% of myelomas and represents malignant plasma cellsthat do not produce any immunoglobulin chains, heavy or light.

A plasma cell disorder related to myeloma is called monoclonal gammopathy of undetermined significance, or MGUS.

  • People with MGUS produce small amounts of monoclonal protein, but they have none of the symptoms or complications of myeloma.
  • MGUS is much more common than myeloma.The incidence of MGUS increases with age. It is uncommon in young individuals and reaches an incidence of approximately3%in people aged 70 years and older.

MGUS isbelieved to be a premyeloma condition, although not all patients with MGUSdevelop myeloma.About 30-40% of people with MGUS, given sufficient time, may progress to develop myeloma.


Myeloma is the second most common blood cancer, but it is not a common cancer. About 15,270 peoplewere expected tobe diagnosed with multiple myeloma in the United States in 2004, almost equally distributed between men and women. About 11,070 Americanswere expected to die of multiple myeloma in 2004.

  • Myeloma is predominantly a cancer of older people. More than 80% of people with myeloma are aged 60 years or older.
  • Myeloma is nearly twice as common in African Americans as in Americans of European, Hispanic, or Asian descent.