What is Multiple Myeloma Multiple myeloma is one of several diseases that are collectively known as plasma cell dyscrasias.

In general, the term myeloma refers to cancer of special types of white blood cells called plasma cells. Plasma cells are important components of the immune system that help the body fight infections caused by microorganisms such as bacteria, viruses, and fungi. Plasma cells are found primarily in the bone marrow and develop from white blood cells called B-lymphocytes. When microorganisms invade the body, B-lymphocytes respond by transforming into plasma cells which, in turn, produce proteins called antibodies that help to destroy the invading microorganisms and, thereby, eradicate the infection. There are five types (classes) of antibodies (immunoglobulins) produced by plasma cells: IgG, IgM, IgA, IgD, and IgE. Each plasma cell produces a specific class of antibodies. Under normal conditions, the body only produces plasma cells when they are needed to help fight off infections. Once the infection has been eliminated from the body, the old plasma cells die off. Certain genetic mutations can cause plasma cells to become abnormal and continue to divide over and over again and, eventually, form a tumor. These abnormal plasma cells, called myeloma cells are cancer cells that produce a specific type of antibody (monoclonal antibody) called M proteins. The monoclonal antibody that is typically overproduced by the myeloma cells is usually of the IgG or IgA variety. Most commonly, a whole monoclonal antibody is produced, however, in about 20% of cases, only a partial antibody called a light chain is produced by the myeloma cells. Light chains do not remain in the circulation and are found mainly in the urine. The M proteins in patients with multiple myeloma can be detected in the blood and/or urine by specialized techniques known as protein electrophoresis andimmunofixation. Since plasma cells originate from the bone marrow, when plasma cells grow out of control, become abnormal myeloma cells, and produce tumors, the tumors usually develop in the bone marrow. If only a single tumor is present, it is called a solitary plasmacytoma. Typically, however, several tumors can be found throughout the bone marrow and, in these cases, the condition is called multiple myeloma. In patients with multiple myeloma, the number of myeloma cells in the bone marrow increases signficantly and usually accounts for more than 20% of the total population of cells found in the bone marrow. The abundance of cancerous plasma cells in the bone marrow can lead to complications including: y Anemia - an abnormally low number of red blood cells in the bloodstream that can cause severe fatigue and weakness. y Thrombocytopenia - an abnormally low number of platelets in the circulation that can lead to bleeding and/or bruising problems. y Leukopenia - an abnormally low number of white blood cells in the circulation that increases the risk for developing severe, lifethreatening infections. y Myeloma bone disease - myeloma cells produce a variety of substances (mediators) that stimulate cells called osteoclasts to resorb (dissolve) bone at a much faster rate than cells called osteoblastscan produce new bone. This increased rate of bone resorption in patients with myeloma can cause weak, brittle bones (osteoporosis) and, thereby, increase the risk for developing fractures. Knowledge is Critical when Dealing with a Life-Altering Condition such as Multiple Myeloma y These 2 classification systems, which play a key role in both planning treatment and predicting the outcome (prognosis) are known as the: o Durie-Salmon staging system o International staging system Understanding the Standard Treatments...and the Treatment Options Because currently there is no known cure for multiple myeloma, understanding the standard treatments - and the treatment options - is critical in attempting to prolong survival and maintain the patient's overall functional ability and quality of life. As you read through the section of the Guidebook that focuses on the treatments for multiple myeloma, you will specifically learn about: y Which patients with multiple myeloma are candidates for an approach known as "watchful waiting", where the progress of the disease is monitored carefully but no specific treatment is required. y The various phases in the treatment of multiple myeloma for patients whose disease has progressed to the point where treatment becomes necessary. These treatment phases are grouped into the following categories: o Initial or induction chemotherapy o Consolidation therapy o Maintenance therapy o Salvage therapy y The role of stem cell transplantation in the management of patients with multiple myeloma, including the risks and benefits of this procedure. y The treatment options available to patients with multiple myeloma who experience a relapse orrecurrence of the disease after initially having gone into remission. y The role of plasmapharesis - the direct removal of abnormal antibody proteins from the bloodstream - in the management of patients with multiple myeloma. y A detailed overview of the risk of infections in people with multiple myeloma, including practical recommendations for reducing the risks of developing potentially life-threatening bacterial, viral, and fungal infections.

The treatment options that are available for the management of patients with multiple myeloma who develop myeloma bone disease - areas of bone destruction caused by multiple myeloma that significantly increase the risk of developing pathologic fractures. y The prognosis (outlook) for people with multiple myeloma and important prognostic factors that have a significant impact in predicting the overall chances of recovery and survival. y The role of complementary and alternative therapies in the management of people with multiple myeloma. y Quality of life issues such as sleep disorders, fatigue, weight loss, and psychological stress that often confront people with multiple myeloma and tips for how to minimize their impact and better cope with these important issues. y Important questions to ask your doctor about multiple myeloma. Plasma cells, also called plasma B cells, plasmocytes, and effector B cells, are white blood cells which produce large volumes of antibodies. They are transported by the blood plasma and the lymphatic system. Like all blood cells, plasma cells ultimately originate in the bone marrow; however, these cells leave the bone marrow as B cells, before terminal differentiation into plasma cells, normally in lymph nodes. y Multiple myeloma (from Greek myelo-, bone marrow), also known as plasma cell myeloma or Kahler's disease (after Otto Kahler), is [1] a cancer ofplasma cells, a type of white blood cell normally responsible for the production of antibodies. Collections of abnormal cells accumulate in bones, where they cause bone lesions (abnormal areas of tissue), and in the bone marrow where they interfere with the production of normal blood cells. Most cases of myeloma also feature the production of a paraprotein, an abnormal antibody that can cause kidney problems and interferes with the production of normal antibodies leading to immunodeficiency. Hypercalcemia (high calcium levels) is often encountered.[1] Myeloma is diagnosed with blood tests (protein electrophoresis, peripheral blood smear), microscopic examination of the bone marrow (bone marrow biopsy), and radiographs of commonly involved bones. Myeloma is generally thought to be incurable, but remissions may be induced with steroids,chemotherapy, thalidomide and stem cell transplants. Newer drugs, such as lenalidomide and bortezomib, are often used in more advanced disease.Radiation therapy is sometimes used to treat bone lesions that are causing symptoms.[1] The disease develops in 1 4 per 100,000 people per year. It is more common in men, and is twice as common in blacks as it is in whites. With conventional treatment, the prognosis is 3 4 years, which may be extended to 5 7 years or longer with advanced treatments. Multiple myeloma is the second most common hematological malignancy (13%) and constitutes 1% of all cancers.[1] Pathophysiology B lymphocytes start in the bone marrow and move to the lymph nodes. As they progress, they mature and display different proteins on their cell surface. When they are activated to secrete antibodies, they are known as plasma cells. Multiple myeloma develops in B lymphocytes after they have left the part of the lymph node known as the germinal center. The normal cell line most closely associated with MM cells is generally taken to be either an activated memory B cell or the precursor to plasma cells, the plasmablast.[9] The immune system keeps the proliferation of B cells and the secretion of antibodies under tight control. When chromosomes and genes are damaged, often through rearrangement, this control is lost. Often, a promoter gene moves (or translocates) to a chromosome where it stimulates an antibody gene to overproduction. A chromosomal translocation between the immunoglobulin heavy chain gene (on chromosome_14, locus q32) and [10] an oncogene (often 11q13, 4p16.3, 6p21, 16q23 and 20q11 ) is frequently observed in patients with multiple myeloma. This mutation results in dysregulation of the oncogene which is thought to be an important initiating event in the pathogenesis of myeloma. The result is proliferation of a plasma cell clone and genomic instability that leads to further mutations and translocations. The chromosome 14 abnormality is observed in about 50% of all cases of myeloma. Deletion of (parts of) chromosome 13 is also observed in about 50% of cases. [11] Production of cytokines ) (especially IL-6) by the plasma cells causes much of their localised damage, such as osteoporosis, and creates a microenvironment in which the malignant cells thrive.Angiogenesis (the attraction of new blood vessels) is increased. The produced antibodies are deposited in various organs, leading to renal failure, polyneuropathy and various other myelomaassociated symptoms.