Multiple myeloma (also known as MM, myeloma, plasma cell myeloma, or as Kahler's disease after Otto Kahler) is a type of cancer of plasma cells which are immune system cells in bone marrow that produce antibodies. Its prognosis, despite therapy, is generally poor, and treatment may involve chemotherapy and stem cell transplant. It is part of the broad group of diseases called hematological malignancies. The International Statistical Classification of Diseases and Related Health Problems (most commonly known by the abbreviation ICD) provides codes to classify diseases and a wide variety of signs, symptoms, abnormal findings, complaints, social circumstances and external causes of injury or disease. ... The International Statistical Classification of Diseases and Related Health Problems 10th Revision (ICD-10) is a coding of diseases and signs, symptoms, abnormal findings, complaints, social circumstances and external causes of injury or diseases, as classified by the World Health Organization (WHO). ... // C00-D48 - Neoplasms (C00-C14) Malignant neoplasms, lip, oral cavity and pharynx (C00) Malignant neoplasm of lip (C01) Malignant neoplasm of base of tongue (C02) Malignant neoplasm of other and unspecified parts of tongue (C03) Malignant neoplasm of gum (C04) Malignant neoplasm of floor of mouth (C05) Malignant neoplasm of... The International Statistical Classification of Diseases and Related Health Problems (most commonly known by the abbreviation ICD) provides codes to classify diseases and a wide variety of signs, symptoms, abnormal findings, complaints, social circumstances and external causes of injury or disease. ... The following is a list of codes for International Statistical Classification of Diseases and Related Health Problems. ... The International Classification of Diseases for Oncology (ICD-O) is a domain specific extension of the International Statistical Classification of Diseases and Related Health Problems for tumor diseases. ... The International Classification of Diseases for Oncology (ICD-O) is a domain specific extension of the International Statistical Classification of Diseases and Related Health Problems for tumor diseases. ... The Mendelian Inheritance in Man project is a database that catalogues all the known diseases with a genetic component, and - when possible - links them to the relevant genes in the human genome. ... The Disease Bold textDatabase is a free website that provides information about the relationships between medical conditions, symptoms, and medications. ... MedlinePlus (medlineplus. ... eMedicine is an online clinical medical knowledge base that was founded in 1996. ... Medical Subject Headings (MeSH) is a huge controlled vocabulary (or metadata system) for the purpose of indexing journal articles and books in the life sciences. ... Otto KahlerAustrian internist, born January 8, 1849, Prague; died January 24, 1893, Vienna. ... Cancer is a class of diseases or disorders characterized by uncontrolled division of cells and the ability of these to spread, either by direct growth into adjacent tissue through invasion, or by implantation into distant sites by metastasis (where cancer cells are transported through the bloodstream or lymphatic system). ... Plasma cells (also called plasma B cells or plasmocytes) are cells of the immune system that secrete large amounts of antibodies. ... A scanning electron microscope image of a single neutrophil (yellow), engulfing anthrax bacteria (orange). ... Each antibody binds to a specific antigen; an interaction similar to a lock and key. ... Prognosis (older Greek πρόγνωσις, modern Greek πρόγνωση - literally fore-knowing, foreseeing) is a medical term denoting the doctors prediction of how a patients disease will progress, and whether there is chance of recovery. ... Chemotherapy is the use of chemical substances to treat disease. ... Bone marrow transplantation (BMT) or hematopoietic stem cell transplantation (HSCT) is a medical procedure in the field of hematology and oncology that involves transplantation of hematopoietic stem cells (HSC). ... Although hematological malignancies are a form of cancer, they are generally treated by specialists in hematology, although in many hospitals oncology specialists also manage these diseases. ...

Clinical features

Because many organs can be affected by myeloma, the symptoms and signs vary greatly. A mnemonic sometimes used to remember the common tetrad of multiple myeloma is CRAB - C = Calcium (elevated), R =Renal failure, A = Anemia, B = Bone lesions.^[1] Myeloma has many possible symptoms, and all symptoms may be due to other causes. They are presented here in decreasing order of incidence. For other uses, see Mnemonic (disambiguation). ...

Bone pain

Myeloma bone pain usually involves the spine and ribs, and worsens with activity. Persistent localized pain may indicate a pathological fracture. Involvement of the vertebrae may lead to spinal cord compression. Myeloma bone disease is due to proliferation of tumor cells and release of IL-6, also known as osteoclast activating factor (OAF), which stimulates osteoclasts to break down bone. These bone lesions are lytic in nature and are best seen in plain radiographs, which may show a "punched-out" resorptive lesions. The breakdown of bone also leads to release of calcium into the blood, leading to hypercalcemia and its associated symptoms. Spinal cord compression develops when the spinal cord is compressed by a tumor, abscess or other lesion. ... Interleukin-6 (IL-6) is a pro-inflammatory cytokine secreted by T cells and macrophages to stimulate immune response to trauma, especially burns or other tissue damage leading to inflammation. ... An osteoclast (from the Greek words for bone and broken) is a type of bone cell that removes bone tissue by removing the bones mineralized matrix. ... For other uses, see Calcium (disambiguation). ... Hypercalcaemia is an elevated calcium level in the blood. ...

Infection

The most common infections are pneumonias and pyelonephritis. Common pneumonia pathogens include S pneumoniae, S aureus, and K pneumoniae, while common pathogens causing pyelonephritis include E.coli and other gram-negative organisms. The increased risk of infection is due to immune deficiency resulting from diffuse hypogammaglobulinemia, which is due to decreased production and increased destruction of normal antibodies. This article is about human pneumonia. ... Pyelonephritis is an ascending urinary tract infection that has reached the pyelum (pelvis) of the kidney (nephros in Greek). ... Binomial name (Klein 1884) Chester 1901 Streptococcus pneumoniae, or pneumococcus, is a Gram-positive, alpha-hemolytic diplococcus bacterium and a member of the genus Streptococcus. ... Binomial name Rosenbach 1884 Staphylococcus aureus , literally Golden Cluster Seed and also known as golden staph, is the most common cause of staph infections. ... Binomial name Klebsiella pneumoniae (Schroeter 1886) Trevisan 1887 Klebsiella pneumoniae is a Gram-negative, nonmotile, encapsulated, lactose-fermenting, facultatively anaerobic, rod-shaped bacterium found in the normal flora of the mouth, skin, and intestines. ... E. coli redirects here. ... Bacteria that are Gram-negative are not stained dark blue or violet by Gram staining, in contrast to Gram-positive bacteria. ... Hypogammaglobulinemia is a type of immune deficiency. ... Each antibody binds to a specific antigen; an interaction similar to a lock and key. ...

Renal failure

Renal failure may develop both acutely and chronically. It is commonly due to hypercalcemia (see above). It may also be due to tubular damage from excretion of light chains, also called Bence Jones proteins, which can manifest as the Fanconi syndrome (type II renal tubular acidosis). Other causes include glomerular deposition of amyloid, hyperuricemia, recurrent infections (pyelonephritis), and local infiltration of tumor cells. Renal failure is the condition in which the kidneys fail to function properly. ... Acute renal failure (ARF) is a rapid loss of renal function due to damage to the kidneys, resulting in retention of nitrogenous (urea and creatinine) and non-nitrogenous waste products that are normally excreted by the kidney. ... Chronic renal failure (CRF, or chronic kidney failure, CKF, or chronic kidney disease, CKD) is a slowly progressive loss of renal function over a period of months or years and defined as an abnormally low glomerular filtration rate, which is usually determined indirectly by the creatinine level in blood serum. ... Hypercalcaemia is an elevated calcium level in the blood. ... Schematic diagram of an typical antibody showing two Ig heavy chains (blue) linked by disulphide bonds to two Ig light chains (green). ... Bence Jones proteins are often found in the blood and urine of patients suffering from a malignant disease of the bone marrow. ... Fanconi syndrome (also known as Fanconis syndrome) is a disorder in which the proximal tubular function of the kidney is impaired, resulting in improper reabsorption of electrolytes and nutrients back into the bloodstream. ... Renal tubular acidosis, or RTA, is a medical condition in which the kidneys fail to dispose of a normal amount of acid into the urine, which may lead to acidosis (where the blood becomes too acidic). ... For other uses, see Amyloid (disambiguation). ... Hyperuricemia is the presence of high levels of uric acid in the blood. ... Pyelonephritis is an ascending urinary tract infection that has reached the pyelum (pelvis) of the kidney (nephros in Greek). ...

Anemia

The anemia found in myeloma is usually normocytic and normochromic. It results from the replacement of normal bone marrow by infiltrating tumor cells and inhibition of normal red blood cell production (hematopoiesis) by cytokines. This article discusses the medical condition. ... Haematopoiesis is the formation of blood cellular components. ... Cytokines are small protein molecules that are the core of communication between immune system cells, and even between immune system cells and cells belonging to other tissue types. ...

Neurological symptoms

Common problems are weakness, confusion and fatigue due to hypercalcemia. Headache, visual changes and retinopathy may be the result of hyperviscosity of the blood depending on the properties of the paraprotein. Finally, there may be radicular pain, loss of bowel or bladder control (due to involvement of spinal cord leading to cord compression) or carpal tunnel syndrome and other neuropathies (due to infiltration of peripheral nerves by amyloid). It may give rise to paraplegia in late presenting cases. Hypercalcaemia is an elevated calcium level in the blood. ... A headache (cephalalgia in medical terminology) is a condition of pain in the head; sometimes neck or upper back pain may also be interpreted as a headache. ... Retinopathy is a general term that refers to some form of non-inflammatory damage to the retina of the eye. ... A paraprotein is an abnormal protein in the urine or blood, most often associated with multiple myeloma. ... Radicular Pain is pain experienced along the dermatome (or sensory distribution) of a nerve due to pressure on the nerve root. ... The Spinal cord nested in the vertebral column. ... This article is about the medical condition. ... Neuropathy strictly speaking is any disease that affects the neurons of the nervous system. ... The peripheral nervous system or PNS, is part of the nervous system, and consists of the nerves and neurons that reside or extend outside the central nervous system--to serve the limbs and organs, for example. ... For other uses, see Amyloid (disambiguation). ... Paraplegia is an impairment in motor and/or sensory function of the lower extremities. ...

Diagnosis

Investigations

The presence of unexplained anemia, kidney dysfunction, a high erythrocyte sedimentation rate (ESR) and a high serum protein (especially raised immunoglobulin) may prompt further testing. A doctor will request protein electrophoresis of the blood and urine, which might show the presence of a paraprotein (monoclonal protein, or M protein) band, with or without reduction of the other (normal) immunoglobulins (known as immune paresis). One type of paraprotein is the Bence Jones protein which is a urinary paraprotein composed of free light chains (see below). Quantitative measurements of the paraprotein are necessary to establish a diagnosis and to monitor the disease. The paraprotein is an abnormal immunoglobulin produced by the tumor clone. Very rarely, the myeloma is nonsecretory (not producing immunoglobulins). This article discusses the medical condition. ... The kidneys are organs that filter wastes (such as urea) from the blood and excrete them, along with water, as urine. ... The erythrocyte sedimentation rate (ESR), also called a sedimentation rate, sed rate or Biernacki Reaction, is a non-specific measure of inflammation that is commonly used as a medical screening test. ... A representation of the 3D structure of myoglobin, showing coloured alpha helices. ... Schematic of antibody binding to an antigen An antibody is a protein complex used by the immune system to identify and neutralize foreign objects like bacteria and viruses. ... Schematic representation of a protein electrophoresis gel In chemistry and medicine, protein electrophoresis is a method of analysing a mixture of proteins by means of gel electrophoresis, mainly in blood serum (blood plasma is not suitable). ... A paraprotein is an abnormal protein in the urine or blood, most often associated with multiple myeloma. ... Bence Jones proteins are often found in the blood and urine of patients suffering from a malignant disease of the bone marrow. ... Schematic of antibody binding to an antigen An antibody is a protein complex used by the immune system to identify and neutralize foreign objects like bacteria and viruses. ...

In theory, multiple myeloma can produce all classes of immunoglobulin, but IgG paraproteins are most common, followed by IgA and IgM. IgD and IgE myeloma are very rare. In addition, light and or heavy chains (the building blocks of antibodies) may be secreted in isolation: κ- or λ-light chains or any of the five types of heavy chains (α-, γ-, δ-, ε- or μ-heavy chains).

Additional findings include: a raised calcium (when osteoclasts are breaking down bone, releasing calcium into the bloodstream), raised serum creatinine due to reduced renal function, which may be due to paraprotein deposition in the kidney. For other uses, see Calcium (disambiguation). ... In medicine (nephrology) renal function is an indication of the state of the kidney and its role in physiology. ... The kidneys are organs that filter wastes (such as urea) from the blood and excrete them, along with water, as urine. ...

Workup

The workup of suspected multiple myeloma includes a skeletal survey. This is a series of X-rays of the skull, axial skeleton and proximal long bones. Myeloma activity sometimes appear as "lytic lesions" (with local disappearance of normal bone due to resorption), and on the skull X-ray as "punched-out lesions" (pepper pot skull). Magnetic resonance imaging (MRI) is more sensitive than simple X-ray in the detection of lytic lesions, and may supersede skeletal survey, especially when vertebral disease is suspected. Occasionally a CT scan is performed to measure the size of soft tissue plasmacytomas. A skeletal survey is a series of X-rays of all the bones in the body, or at least the axial skeleton and the large cortical bones. ... In the NATO phonetic alphabet, X-ray represents the letter X. An X-ray picture (radiograph) taken by Röntgen An X-ray is a form of electromagnetic radiation with a wavelength approximately in the range of 5 pm to 10 nanometers (corresponding to frequencies in the range 30 PHz... “MRI” redirects here. ... CAT apparatus in a hospital Computed axial tomography (CAT), computer-assisted tomography, computed tomography, CT, or body section roentgenography is the process of using digital processing to generate a three-dimensional image of the internals of an object from a large series of two-dimensional X-ray images taken around...

A bone marrow biopsy is usually performed to estimate the percentage of bone marrow occupied by plasma cells. This percentage is used in the diagnostic criteria for myeloma. Immunohistochemistry (staining particular cell types using antibodies against surface proteins) can detect plasma cells which express immunoglobulin in the cytoplasm but usually not on the surface; myeloma cells are typically CD56, CD38, CD138 positive and CD19 and CD45 negative.^[1] Cytogenetics may also be performed in myeloma for prognostic purposes. A bone marrow biopsy is a medical procedure used as part of a test in the diagnosis of several conditions including leukemia. ... Immunohistochemistry or IHC refers to the process of localizing proteins in cells of a tissue section exploiting the principle of antibodies binding specifically to antigens in biological tissues. ... Neural Cell Adhesion Molecule (NCAM, also the cluster of differentiation CD56) is a homophilic binding glycoprotein expressed on the surface of neurons, glia and skeletal muscle. ... CD38 (cluster of differentiation 38) is a glycoprotein found on the surface of many immune cells (white blood cells), including CD4+, CD8+, B and natural killer cells. ... Syndecan 1 is a proteoglycan. ... The introduction to this article provides insufficient context for those unfamiliar with the subject matter. ... In immunology, the CD45 antigen (CD stands for cluster of differentiation) is a protein which is a leucocyte common antigen, a type I transmembrane protein present on all differentiated hematopoietic cells except erythrocytes that assists in the activation of those cells (a form of co-stimulation). ... A metaphase cell positive for the bcr/abl rearrangement using FISH Cytogenetics is the study of the structure of chromosome material. ...

Other useful laboratory tests include quantitative measurement of IgA, IgG, IgM (immunoglobulins) to look for immune paresis, and β2-microglobulin which provides prognostic information. On peripheral blood smear the rouleaux formation of red blood cells is commonly seen. IGA may stand for: Koji Igarashi, a video game producer Interactive genetic algorithm International Geothermal Association Independent Glass Association International Gothic Association International Gamers Award International Goat Association Irish Games Association Irish Geological Association ImmunoGlobulin A - see IgA nephritis which is a renal disease IGA (supermarkets) Independent Grocers Association or... Schematic of antibody binding to an antigen An antibody is a protein complex used by the immune system to identify and neutralize foreign objects like bacteria and viruses. ... IGM might be an acronym or abbreviation for: The polymeric immunoglobulin, IgM International Grandmaster, a chess ranking intergalactic medium Intragroup medium - see: Intracluster medium IG Metall - the dominant German metalworkers union IGM is an acronym created by Robinson Technologies for several early BBS door games, including Legend of the Red... Schematic of antibody binding to an antigen An antibody is a protein complex used by the immune system to identify and neutralize foreign objects like bacteria and viruses. ...

The recent introduction of a commercial immunoassay for measurement of free light chains potentially offers an improvement in monitoring disease progression and response to treatment, particularly where the paraprotein is difficult to measure accurately by electrophoresis (for example in light chain myeloma, or where the paraprotein level is very low). Initial research also suggests that measurement of free light chains may also be used, in conjunction with other markers, for assessment of the risk of progression from monoclonal gammopathy of undetermined significance (MGUS) to multiple myeloma.^{[citation needed]} Monoclonal gammopathy of undetermined significance (MGUS, unknown or uncertain may be substituted for undertermined) is a condition in which a low or non-quantifiable level of a monoclonal paraprotein is detected in the blood by means of protein electrophoresis. ...

Diagnostic criteria

In 2003, the International Myeloma Working Group^[1] agreed on diagnostic criteria for symptomatic myeloma, asymptomatic myeloma and MGUS (monoclonal gammopathy of undetermined significance): Year 2003 (MMIII) was a common year starting on Wednesday of the Gregorian calendar. ... Monoclonal gammopathy of undetermined significance (MGUS, unknown or uncertain may be substituted for undertermined) is a condition in which a low or non-quantifiable level of a monoclonal paraprotein is detected in the blood by means of protein electrophoresis. ...

• Symptomatic myeloma:
  1. Clonal plasma cells >10% on bone marrow biopsy or (in any quantity) in a biopsy from other tissues (plasmacytoma)
  2. A monoclonal protein (paraprotein) in either serum or urine
  3. Evidence of end-organ damage (related organ or tissue impairment, ROTI):
     • Hypercalcemia (corrected calcium >2.75 mmol/L)
     • Renal insufficiency attributable to myeloma
     • Anemia (hemoglobin <10 g/dL)
     • Bone lesions (lytic lesions or osteoporosis with compression fractures)
     • Frequent severe infections (>2 a year)
     • Amyloidosis of other organs
     • Hyperviscosity syndrome
• Asymptomatic myeloma:
  1. Serum paraprotein >30 g/L AND/OR
  2. Clonal plasma cells >10% on bone marrow biopsy AND
  3. NO myeloma-related organ or tissue impairment
• Monoclonal gammopathy of undetermined significance (MGUS):
  1. Serum paraprotein <30 g/L AND/OR
  2. Clonal plasma cells <10% on bone marrow biopsy AND
  3. NO myeloma-related organ or tissue impairment

Related conditions include solitary plasmacytoma (a single tumor of plasma cells, typically treated with irradiation), plasma cell dyscrasia (where only the antibodies produce symptoms, e.g. AL amyloidosis), and POEMS syndrome (peripheral neuropathy, organomegaly, endocrinopathy, monoclonal plasma cell disorder, skin changes). This article does not cite any references or sources. ... Brain biopsy A biopsy (in Greek: bios = life and opsy = look/appearance) is a medical test involving the removal of cells or tissues for examination. ... Plasmacytoma refers to a malignant monoclonal plasma cell tumor growing either in bone or soft tissue. ... Monoclonal antibodies (mAb) are antibodies that are identical because they were produced by one type of immune cell, all clones of a single parent cell. ... A paraprotein is an abnormal protein in the urine or blood, most often associated with multiple myeloma. ... Blood plasma is the liquid component of blood, in which the blood cells are suspended. ... This article or section is in need of attention from an expert on the subject. ... Hypercalcaemia is an elevated calcium level in the blood. ... Renal failure is when the kidneys fail to function properly. ... This article discusses the medical condition. ... A lesion is a non-specific term referring to abnormal tissue in the body. ... Osteoporosis is a disease of bone in which the bone mineral density (BMD) is reduced, bone microarchitecture is disrupted, and the amount and variety of non-collagenous proteins in bone is altered. ... Infection is also the title of an episode of the television series Babylon 5; see Infection (Babylon 5). ... Hyperviscosity syndrome is an increase in the viscosity of the blood. ... Plasmacytoma refers to a malignant monoclonal plasma cell tumor growing either in bone or soft tissue. ... Dyscrasia (from Greek Dyskrasia, meaning bad mixture), in Ancient Greek medicine, is the imbalance of the four humours, and was believed to be the direct cause of all disease. ... POEMS syndrome is a rare syndrome, the main features of which are polyneuropathy (peripheral nerve damage), organomegaly (enlargement of liver or spleen), endocrinopathy (damage to hormone-producing glands)/edema, M-protein (an abnormal antibody) and skin changes. ...

Staging

International Staging System

The International Staging System (ISS) for myeloma was published by the International Myeloma Working Group in 2003 ^[2]:

• Stage I: β₂-microglobulin (β2M) < 3.5 mg/L, albumin >= 3.5 g/dL
• Stage II: β2M < 3.5 and albumin < 3.5; or β2M between 3.5 and 5.5
• Stage III: β2M > 5.5

Durie-Salmon staging system

First published in 1975, the Durie-Salmon staging system ^[3] is still in use, but has largely been superseded by the simpler ISS: A small protein that forms part of the Class I MHC (Major Histocompatibility Complex). ... You may be looking for albumen, or egg white. ...

• stage 1: all of
  • Hb > 10g/dL
  • normal calcium
  • Skeletal survey: normal or single plasmacytoma or osteoporosis
  • Serum paraprotein level < 5 g/dL if IgG, < 3 g/dL if IgA
  • Urinary light chain excretion < 4 g/24h
• stage 2: fulfilling the criteria of neither 1 nor 3
• stage 3: one or more of
  • Hb < 8.5g/dL
  • high calcium > 12mg/dL
  • Skeletal survey: 3 or more lytic bone lesions
  • Serum paraprotein >7g/dL if IgG, > 5 g/dL if IgA
  • Urinary light chain excretion > 12g/24h

Stages 1, 2 and 3 of the Durie-Salmon staging system can be divided into A or B depending on serum creatinine:

• A: serum creatinine < 2mg/dL (< 177 umol/L)
• B: serum creatinine > 2mg/dL (> 177 umol/L)

Pathophysiology

Multiple myeloma develops in post-germinal center B lymphocytes. B cells are lymphocytes that play a large role in the humoral immune response (as opposed to the cell-mediated immune response). ...

A chromosomal translocation between the immunoglobulin heavy chain gene (on the fourteenth chromosome, locus 14q32) and an oncogene (often 11q13, 4p16.3, 6p21, 16q23 and 20q11^[4]) 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) the thirteenth chromosome is also observed in about 50% of cases. Chromosomal translocation of the 4th and 20th chromosome. ... Figure 1: A representation of a condensed eukaryotic chromosome, as seen during cell division. ... An oncogene is a modified gene that increases the malignancy of a tumor cell. ...

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. Cytokines are a group of proteins and peptides that are used in organisms as signaling compounds. ... Interleukin-6 (IL-6) is a pro-inflammatory cytokine secreted by T cells and macrophages to stimulate immune response to trauma, especially burns or other tissue damage leading to inflammation. ... Osteoporosis is a disease of bone in which the bone mineral density (BMD) is reduced, bone microarchitecture is disrupted, and the amount and variety of non-collagenous proteins in bone is altered. ... Angiogenesis is the physiological process involving the growth of new blood vessels from pre-existing vessels. ...

The produced antibodies are deposited in various organs, leading to renal failure, polyneuropathy and various other myeloma-associated symptoms.

Epidemiology

There are approximately 45,000 people in the United States living with multiple myeloma, and the American Cancer Society estimates that approximately 14,600 new cases of myeloma are diagnosed each year in the United States. It follows from here that the average survival at diagnosis is about three years. The American Cancer Society (ACS) is a medical organization with a corporate attitude in the United States. ...

Multiple myeloma is the second most prevalent blood cancer (10%) after non-Hodgkin's lymphoma. It represents approximately 1% of all cancers and 2% of all cancer deaths. Although the peak age of onset of multiple myeloma is 65 to 70 years of age, recent statistics indicate both increasing incidence and earlier age of onset. Non-Hodgkins lymphoma is a type of cancer. ...

Multiple myeloma affects slightly more men than women. African Americans and Native Pacific Islanders have the highest reported incidence of this disease in the United States and Asians the lowest. Results of a recent study found the incidence of myeloma to be 9.5 cases per 100,000 African Americans and 4.1 cases per 100,000 Caucasian Americans. Among African Americans, myeloma is one of the top 10 leading causes of cancer death.

Treatment

Treatment for multiple myeloma is focused on disease containment and suppression. If the disease is completely asymptomatic (i.e. there is a paraprotein and an abnormal bone marrow population but no end-organ damage), treatment may be deferred.

Although allogeneic stem cell transplant might cure the cancer, it is considered investigational given the high treatment-related mortality of 5-10% associated with the procedure. In addition to direct treatment of the plasma cell proliferation, bisphosphonates (e.g. pamidronate or zoledronic acid) are routinely administered to prevent fractures and erythropoietin to treat anemia. Bone marrow transplantation or hematopoietic stem cell transplantation (HSCT) is a medical procedure in the field of hematology and oncology that involves transplantation of hematopoietic stem cells (HSC). ... In pharmacology, bisphosphonates (also called: diphosphonates) is a class of drugs that inhibits the resorption of bone. ... Pamidronate disodium (brand name Aredia®) is a bisphosphonate used to prevent bone loss, and treat osteoporosis. ... Zoledronate (Zometa®, Novartis) is a bisphosphonate, used to prevent osteoporosis and skeletal fractures, particularly in patients with cancers such as multiple myeloma and prostate cancer. ... Erythropoietin (IPA pronunciation: , alternative pronunciations: ) or EPO is a glycoprotein hormone that is a cytokine for erythrocyte (red blood cell) precursors in the bone marrow. ...

Initial therapy

Initial treatment is aimed at treating symptoms and reducing disease burden. Commonly used induction regimens include dexamethasone with or without thalidomide and cyclophosphamide, and VAD (vincristine, adriamycin, and dexamethasone). Low-dose therapy with melphalan combined with prednisone can be used to palliate symptoms in patients who cannot tolerate aggressive therapy. Plasmapheresis can be used to treat symptomatic protein proliferation (hyperviscosity syndrome). Dexamethasone is a potent synthetic member of the glucocorticoid class of steroid hormones. ... This article is about the drug. ... Cyclophosphamide (the generic name for Cytoxan, Neosar) is a nitrogen mustard alkylating agent, used to treat various types of cancer and some autoimmune disorders. ... Vincristine (Oncovin®), also known as leurocristine, is a vinca alkaloid from the Madagascar periwinkle (Catharanthus roseus, formerly Vinca rosea and hence its name). ... Doxorubicin or Adriamycin® or hydroxyldaunorubicin is a DNA-interacting drug widely used in chemotherapy. ... Melphalan hydrochloride ( Alkeran®) is a chemotherapy drug belonging to the class of nitrogen mustard alkylating agents. ... Plasmapheresis (from the Greek plasma, something molded, and apheresis, taking away) is the removal, treatment, and return of (components of) blood plasma from blood circulation. ... Hyperviscosity syndrome is an increase in the viscosity of the blood. ...

In younger patients, therapy may include high-dose chemotherapy, melphalan, and autologous stem cell transplantation. This can be given in tandem fashion, i.e. an autologous transplant followed by a second transplant. Nonmyeloablative (or "mini") allogeneic stem cell transplantation is being investigated as an alternative to autologous stem cell transplant, or as part of a tandem transplant following an autologous transplant (also known as an "auto-mini" tandem transplant). Chemotherapy is the use of chemical substances to treat disease. ... Melphalan hydrochloride ( Alkeran®) is a chemotherapy drug belonging to the class of nitrogen mustard alkylating agents. ... Bone marrow transplantation or hematopoietic stem cell transplantation (HSCT) is a medical procedure in the field of hematology and oncology that involves transplantation of hematopoietic stem cells (HSC). ... Bone marrow transplantation or hematopoietic stem cell transplantation (HSCT) is a medical procedure in the field of hematology and oncology that involves transplantation of hematopoietic stem cells (HSC). ...

A 2007 trial indicated that the addition of thalidomide to reduced-intensity chemotherapy (melphalan and prednisone, MP) in patients between 65-75 led to a marked prolongation (median 51 versus 33 months) in survival. Reduced intensity melphalan followed by a stem cell transplant was inferior to the MP-thalidomide regimen (median survival 38 months).^[5]

Relapse

The natural history of myeloma is of relapse following treatment. Depending on the patient's condition, the prior treatment modalities used and the duration of remission, options for relapsed disease include re-treatment with the original agent, use of other agents (such as melphalan, cyclophosphamide, thalidomide or dexamethasone, alone or in combination), and a second autologous stem cell transplant.

Later in the course of the disease, "treatment resistance" occurs. This may be a reversible effect,^[4] and some new treatment modalities may re-sensitize the tumor to standard therapy. For patients with relapsed disease, bortezomib (or Velcade®) is a recent addition to the therapeutic arsenal, especially as second line therapy. Bortezomib is a proteasome inhibitor. Finally, lenalidomide (or Revlimid®), a less toxic thalidomide analog, is showing promise for treating myeloma. Bortezomib (originally PS-341 and marketed as Velcade by Millennium Pharmaceuticals) is the first therapeutic proteasome inhibitor to be tested in humans. ... A proteasome is a barrel-shaped multi-protein complex that can digest other proteins into short polypeptides and amino acids in an ATP-driven reaction. ... Lenalidomide (initially known as CC-5013 and marketed as Revlimid® by Celgene) is a derivative of thalidomide introduced in 2004. ...

Renal failure in multiple myeloma can be acute (reversible) or chronic (irreversible). Acute renal failure typically resolves when the calcium and paraprotein levels are brought under control. Treatment of chronic renal failure is dependent on the type of renal failure and may involve dialysis. Acute renal failure (ARF) is a rapid loss of renal function due to damage to the kidneys, resulting in retention of nitrogenous (urea and creatinine) and non-nitrogenous waste products that are normally excreted by the kidney. ... Chronic renal failure (CRF, or chronic kidney failure, CKF, or chronic kidney disease, CKD) is a slowly progressive loss of renal function over a period of months or years and defined as an abnormally low glomerular filtration rate, which is usually determined indirectly by the creatinine level in blood serum. ... In medicine, dialysis is a type of renal replacement therapy which is used to provide an artificial replacement for lost kidney function due to renal failure. ...

Prognosis

The International Staging System can help to predict survival, with a median survival of 62 months for stage 1 disease, 45 months for stage 2 disease, and 29 months for stage 3 disease.^[2]

Cytogenetic analysis of myeloma cells may be of prognostic value, with deletion of chromosome 13, non-hyperdiploidy and the balanced translocations t(4;14) and t(14;16) conferring a poorer prognosis. The 11q13 and 6p21 cytogenetic abnormalities are associated with a better prognosis. A metaphase cell positive for the bcr/abl rearrangement using FISH Cytogenetics is the study of the structure of chromosome material. ... Prognosis (older Greek πρόγνωσις, modern Greek πρόγνωση - literally fore-knowing, foreseeing) is a medical term denoting the doctors prediction of how a patients disease will progress, and whether there is chance of recovery. ...

Prognostic markers such as these are always generated by retrospective analyses, and it is likely that new treatment developments will improve the outlook for those with traditionally 'poor-risk' disease.

See also

• Waldenström macroglobulinemia
• Multiple Myeloma Research Consortium
• Multiple Myeloma Research Foundation
• MM Support Network

Waldenström macroglobulinemia (WM) is cancer involving a subtype of white blood cells called lymphocytes. ... The Multiple Myeloma Research Consortium (MMRC) is a unique research model that was developed to accelerate the development of novel, cutting-edge treatments for patients afflicted by multiple myeloma by catalyzing, promoting, and facilitating collaborative research between industry and academia. ... The Multiple Myeloma Research Foundation or MMRF is a non-profit organization based in New Canaan, Connecticut dedicated to accelerating the search for a cure of multiple myeloma. ... The Multiple Myeloma Research Consortium (MMRC) is a unique research model that was developed to accelerate the development of novel, cutting-edge treatments for patients afflicted by multiple myeloma by catalyzing, promoting, and facilitating collaborative research between industry and academia. ...

References

1. ^ ^{a b c} International Myeloma Working Group. Criteria for the classification of monoclonal gammopathies, multiple myeloma and related disorders: a report of the International Myeloma Working Group. Br J Haematol 2003;121:749-57. PMID 12780789.
2. ^ ^{a b} Greipp PR, San Miguel J, Fonseca R, Avet-Loiseau H, Jacobson JL, Rasmussen E, Crowley J, Durie BMG. Development of an international prognostic index (IPI) for myeloma: report of the international myeloma working group. Hematology Journal 2003;4:S42. NLM ID 100965523.
3. ^ Durie BG, Salmon SE. A clinical staging system for multiple myeloma. Correlation of measured myeloma cell mass with presenting clinical features, response to treatment and survival. Cancer 1975;36:842–854. PMID 1182674.
4. ^ ^{a b} Kyle RA, Rajkumar SV. Multiple myeloma. N Engl J Med 2004;351:1860-73. PMID 15509819.
5. ^ Facon T, Mary JY, Hulin C et al (2007). "Melphalan and prednisone plus thalidomide versus melphalan and prednisone alone or reduced-intensity autologous stem cell transplantation in elderly patients with multiple myeloma (IFM 99–06): a randomised trial". Lancet 370: 1209-1218. 

The New England Journal of Medicine (NEJM) is a peer-reviewed medical journal published by the Massachusetts Medical Society. ...

External links

• The Velcade Three Myeloma patients compaigning for access to a life prolonging cancer drug
• Myeloma UK
• International Myeloma Foundation
• Multiple Myeloma Research Foundation
• MM Support Network
• Myeloma Euronet - European Network of Myeloma Patient Groups
• The Leukemia & Lymphoma Society's Myeloma Page