Multiple myeloma , also known as plasma cell myeloma , is a plasma cell cancer, a type of white blood cell that is usually responsible for producing antibodies. Often, no symptoms are seen at first. When advanced, bone pain, bleeding, frequent infections, and anemia may occur. Complications may include amyloidosis.
The cause is unknown. Risk factors include drinking alcohol, obesity, radiation exposure, family history, and certain chemicals. The underlying mechanism involves abnormal plasma cells producing abnormal antibodies that can cause kidney problems and too much blood. Plasma cells can also form mass in the bone marrow or soft tissue. When only one mass is present, it is known as a plasmacytoma while more than one is known as multiple myeloma. Multiple myeloma diagnosed based on blood or urine tests find abnormal antibodies, bone marrow biopsy found cancer plasma cells, and medical imaging found bone lesions. Another common finding is high blood calcium levels.
Multiple myeloma is considered treatable, but is generally incurable. Remission can be carried with steroids, chemotherapy, thalidomide or lenalidomide, and stem cell transplantation. Bisphosphonates and radiation therapy are sometimes used to relieve pain from bone lesions.
Globally, multiple myeloma affects 488,000 people and result in 101,100 deaths by 2015. In the United States, it develops at 6.5 per 100,000 people per year and 0.7% of people are affected at some point in their lives. It usually occurs around the age of 61 years and is more common in men than women. Without treatment, typical survival is seven months. With current treatments, survival is usually 4-5 years. This provides a five-year survival rate of about 49%. The word myeloma comes from the Greek myelo - which means "marrow" and -oma meaning "tumor".
Video Multiple myeloma
Signs and symptoms
Since many organs can be affected by myeloma, symptoms and signs vary widely. Mnemonic which is sometimes used to remember some common symptoms of multiple myeloma is CRAB: C = calcium (elevated), R = renal failure, A = anemia, B = bone lesion. Myeloma has many other possible symptoms, including opportunistic infections (eg, pneumonia) and weight loss. Symptoms of crabs and the proliferation of monoclonal plasma cells in the bone marrow are part of multiple myeloma diagnostic criteria.
Bone pain
Bone pain affects nearly 70% of patients and is the most common symptom. Bone myeloma pain usually involves the spine and ribs, and worsens with activity. Permanent local pain may indicate pathologic fracture. Vertebral involvement can lead to spinal cord compression or kyphosis. Myeloma bone disease is caused by overexpression of receptor activator for nuclear factor? B ligand (RANKL) by bone marrow stroma. RANKL activates osteoclasts, which absorb bones. The resulting bone lesions are lytic (natural causes of damage), and are best seen in plain photographs, which may exhibit "puncture-out" resorptive lesions (including the appearance of "crescent rays" on radiography). The decomposition of bone also leads to the release of calcium into the blood, leading to hypercalcemia and related symptoms.
Anemia
Anemia found in myeloma is usually normocytic and normochromic. This results from normal bone marrow replacement by infiltration tumor cells and inhibition of normal production of red blood cells (hematopoiesis) by cytokines.
Kidney failure
Kidney failure may develop acutely and chronically.
The most common cause of renal failure in multiple myeloma is due to the protein secreted by malignant cells. Myeloma cells produce monoclonal proteins of various types, most commonly immunoglobulins (antibodies) and free light chains, which produce abnormally high levels of abnormal protein in the blood. Depending on the size of this protein, they can be excreted through the kidneys. The kidneys can be damaged by the effects of protein or light chains. Increased bone resorption leads to hypercalcaemia and causes nephrocalcinosis, thus contributing to renal failure. Amyloidosis is a distant third in its cause. Patients with amyloidosis have high levels of amyloid proteins that can be excreted through the kidneys and cause damage to the kidneys and other organs.
The light chain produces many effects that can manifest as Fanconi syndrome (type II tubular tubular kidney).
Infection
The most common infections are pneumonia and pyelonephritis. Common pneumonia pathogens include S. pneumoniae, S. aureus and pneumoniae, while common pathogens cause pyelonephritis including E. coli and other Gram-negative organisms. The greatest risk period for infection occurs in the first few months after the onset of chemotherapy. Increased risk of infection is due to immune deficiency. Although total immunoglobulin level is usually increased in multiple myeloma, the majority of monoclonal antibody antibodies are ineffective from clonal plasma cells. Selected patient groups with documented hypogamaglobulinemia may benefit from replacement immunoglobulin therapy to reduce the risk of infection.
Neurological symptoms
Some symptoms (eg, weakness, confusion, and fatigue) may be caused by anemia or hypercalcaemia. Headaches, visual changes, and retinopathy may be the result of blood hyperviscosity depending on the nature of the paraprotein. Finally, radicular pain, loss of bowel or bladder control (due to spinal cord involvement leads to cord compression) or carpal tunnel syndrome, and other neuropathies (due to peripheral peripheral nerve infiltration by amyloid) may occur. This can lead to paraplegia in late-presentation cases.
When the disease is well controlled, neurologic symptoms can result from current treatments, some of which can cause peripheral neuropathy, which manifests itself as numbness or pain in the hands, feet, and lower legs.
Maps Multiple myeloma
Cause
The cause is generally unknown.
Risk factors
- Monoclonal gammopathy with immeasurable significance (MGUS) increases the risk of developing multiple myeloma. MGUS changes into multiple myeloma at levels of 1% to 2% per year, and almost all cases of multiple myeloma are preceded by MGUS.
- Some myeloma that burns increases the risk of developing multiple myeloma. Individuals diagnosed with this premalignant disorder develop multiple myeloma at a rate of 10% per year for the first 5 years, 3% per year for the next 5 years, and then 1% per year.
- Obesity associated with multiple myeloma with any increase in body mass index of 5 increases the risk by 11%.
A family predisposition to myeloma exists. Hyperphosphorylation of a number of paratargan proteins - an autosomal inherited tendency dominant, emerges a common mechanism in this family. This tendency is more common in African-American patients with myeloma and may contribute to higher myeloma levels in this group.
Pathophysiology
B lymphocytes begin in the bone marrow and move to the lymph nodes. As they progress, they mature and display different proteins on the surface of their cells. When they are activated to secrete antibodies, they are known as plasma cells.
Multiple myeloma develops in B lymphocytes after they leave part of the lymph nodes known as germinal centers. Normal cell lines most closely related to MM cells are generally regarded as cell B active memory or plasma cell precursors, plasmablast.
The immune system keeps B cell proliferation and antibody secretion under strict control. When chromosomes and genes are damaged, often by rearrangement, this control is lost. Often, the promoter's genes move (or translocate) to the chromosome where it stimulates the antibody gene for overproduction.
Translocation of chromosomes between the immunoglobulin chain gene (on chromosome 14, locus q32) and oncogene (often 11q13, 4p16.3, 6p21, 16q23 and 20q11) are often observed in patients with multiple myeloma. This mutation results in the dysregulation of oncogens which is considered an important initiation event in the pathogenesis of myeloma. The result is the proliferation of plasma cell clones and genomic instability leading to further mutations and translocations. Chromosomal abnormalities 14 are observed in about 50% of all myeloma cases. Removal of chromosome 13 part is also observed in about 50% of cases.
The production of cytokines (especially IL-6) by plasma cells causes much of their local damage, such as osteoporosis, and creates a microenvironment in which malignant cells develop. Angiogenesis (the formation of new blood vessels) increases.
The resulting antibodies are stored in various organs, leading to kidney failure, polyneuropathy, and other myeloma-related symptoms.
Epigenetic
In a study investigating the DNA methylation profile of some myeloma cells and normal plasma cells, a gradual demethylation from stem cells to plasma cells was observed. The observed methylation pattern of CpG in the intronic region with elevated chromatin-related markers in multiple myeloma is similar to that of undifferentiated precursors and stem cells. These results can represent the epigenetic reprogramming of de novo in multiple myeloma, leading to the acquisition of methylation patterns associated with stemness.
Genetics
Mutations in a number of genes have been linked to this condition. These include ATM, BRAF, CCND1, DIS3, FAM46C, KRAS, NRAS and TP53.
Development
The recently described genetic and epigenetic changes occur gradually. The initial change, often involving one of the chromosomal translocations called 14, forms a clone of bone marrow plasma cells that causes an asymptomatic disturbance called monoclonal gammopathy of unspecified significance (MGUS). MGUS is a pramalignant disorder characterized by an increase in plasma cell count in the bone marrow or circulating immunoglobulin myeloma protein. Genetic or epigenic changes further produce new clones of bone marrow plasma cells, usually offspring of the original clones, which lead to more serious but still asymptomatic premalignant disorders called smoldering multiple myeloma. Some mild myeloma is characterized by an increase in the number of bone marrow plasma cells or myeloma protein levels circulating above that are seen in MGUS.
Genetic and epigenetic changes subsequently lead to more aggressive new plasma cell clones that cause a further increase in circulating myeloma protein levels, an increase in the number of bone marrow plasma cells, or one or more specific developments. a series of "CRAB" symptoms (see the diagnostic section below). This last change is the basis for diagnosing multiple myeloma maligna and treating illness.
In a small percentage of multiple myeloma cases, genetic and epigenetic changes further lead to the development of plasma clones moving from the bone marrow into the circulation, invading the distant tissues, thereby causing the most virulent of all plasma cell dyscrasias, plasma cell leukemia. Thus, fundamental genetic instability in plasma cells or their precursors leads to the development of the following disorders:
Being asymptomatic, monoclonal gammapathy with unexplained significance and multiple smears of myeloma are usually accidentally diagnosed by detecting myeloma proteins in serum protein electrophoresis tests performed for other purposes. Monoclonal gammopathy of undetermined significance is a relatively stable condition affecting 3% of people aged 50 and 5% of people aged 70 years; it develops into multiple myeloma at a rate of 0.5-1% of cases per year; smoldering multiple myeloma do so at a rate of 10% per year for the first 5 years but then fall sharply to 3% per year over the next 5 years and then to 1% per year.
Overall, about 2-4% of cases of multiple myeloma eventually develop into plasma cell leukemia.
Diagnosis
The presence of unexplained anemia, renal dysfunction, high erythrocyte sedimentation (ESR), lytic bone lesion, increased beta-2 microglobulin, or high serum protein (especially globulin or immunoglobulin) may trigger further tests.
Blood tests
Globulin levels may be normal in existing disease. A doctor will ask for blood and urine electrophoresis proteins, which may indicate the presence of a paraprotein band (monoclonal protein, or M protein), with or without other immunoglobulin (normal) reductions (known as immune paresis). One type of paraprotein is the Bence Jones protein which is a urine paraprotein composed of light free chains (see below). Quantitative measurements of paraproteins are needed to make the diagnosis and to monitor disease. Paraproteins are abnormal immunoglobulins produced by tumor clones.
In theory, multiple myeloma can produce all classes of immunoglobulins, but paraprotein IgG is the most common, followed by IgA and IgM. IgD and myeloma IgE are very rare. In addition, light and/or heavy chains (antibody building blocks) can be secreted separately: - or light chains-or any of five types of heavy (? -, -, -, - or heavy-chain) chains. Patients without evidence of monoclonal protein may have "non-secretory" mieloma (not producing immunoglobulins); this represents about 3% of all myeloma multiple patients.
Additional findings may include: increased calcium (when osteoclasts break bone, release calcium into the bloodstream), increase serum creatinine due to reduced kidney function, primarily due to decomposition of paraprotein in the kidney, although the cast also contains complete immunoglobulin, protein and Tamm albumin -Horsfall.
Other useful laboratory tests include quantitative measurements of IgA, IgG, IgM (immunoglobulin) to seek immune paresis, and beta-2 microglobulin that provides prognostic information. In peripheral blood smear, rouleaux formation of red blood cells is often seen, although this is not specific.
The recent introduction of commercial immunoassay for the measurement of free light chains has the potential to offer an increase in monitoring disease progression and response to treatment, especially where paraproteins are difficult to measure accurately by electrophoresis (eg in mild chain myeloma, or where the paraprotein level is very low). Initial studies have also shown that free-chain measurements of light can also be used, in conjunction with other markers, to assess the developmental risks of monoclonal gammopathy of undetermined significance (MGUS) to multiple myeloma.
This test, serum-free light chain test, was recently recommended by the International Myeloma Working Group for screening, diagnosis, prognosis, and plasma plasma cell dysregulation monitoring.
Histopathology
Bone marrow biopsy is usually done to estimate the percentage of bone marrow that is occupied by plasma cells. This percentage is used in the diagnostic criteria for myeloma. Immunohistochemistry (staining of certain cell types using antibodies to surface proteins) can detect plasma cells that express immunoglobulins in the cytoplasm and occasionally on the cell surface; myeloma cells are usually CD56, CD38, CD138, CD319 positive and CD19 and CD45 negative. Cytogenetics may also be performed in myeloma for prognostic purposes, including myeloma-specific FISH and virtual karyotype.
Plasma cells seen in multiple myeloma have several possible morphologies. First, they can have normal plasma cell appearance: large cells are two or three times the size of peripheral lymphocytes. Because they are actively producing antibodies, Golgi apparatus will usually produce brightly colored areas adjacent to the nucleus, called halo perinuklear. The single nucleus (with a single nucleolus with nuclear vesicular chromatin) is eccentric, displaced by abundant cytoplasm. Other common visible morphologies, but those unusual in normal plasma cells, include:
- Strange cells, which are multinucleated.
- Mott cells, containing multiple clumped cytoplasm droplets or other inclusions (sometimes confused with auer stems, usually seen in myeloid explosions)
- The fire cells, having a fiery red cytoplasm.
Historically, CD138 has been used to isolate myeloma cells for diagnostic purposes. However, this antigen disappears rapidly ex vivo. Recently, however, it was found that the surface of CD319 antigen (SLAMF7) is much more stable and allows strong insulation of malignant plasma cells from delayed or even cryopreserved samples.
The prognosis varies greatly depending on various risk factors. The Mayo Clinic has developed a risk stratification model called Stratification Mayo for Myeloma and Risk-adapted Therapy (mSMART) that divides people into high risk categories and standard risks. People with chromosome 13 or hypodiploidy removal by conventional cytogenetics, t (4; 14), t (14; 16) or 17p- by molecular genetic studies, or with high plasma cell labeling index (3% or more) are considered to have high risk myeloma.
Medical description
A person's diagnostic examination with multiple myeloma assumptions usually includes skeletal surveys. This is a series of X-ray skulls, axial skeletons and proximal long bones. Myeloma activity occasionally presents as a "lytic lesion" (with normal localized bone loss due to resorption), and to the X-ray skull as "pitted lesion" (crown skull). Lesions can also be sclerotic seen as radiodens. Overall, the myeloma radiodensity is between -30 and 120 units of Hounsfield (HU). Magnetic resonance imaging (MRI) is more sensitive than simple X-rays in detecting lysis lesions, and may replace skeletal surveys, especially when vertebral disease is suspected. Sometimes a CT scan is performed to measure the size of a soft tissue plasmasitoma. Bone scan is usually not an additional value in the examination of myeloma patients (no new bone formation; lytic lesions are not well visualized in bone scan).
Diagnostic criteria
In 2003, the International Myeloma Working Group approved diagnostic criteria for symptomatic myeloma, asymptomatic myeloma and MGUS, which was later updated in 2009:
- Symptomatic myeloma (all three criteria must be met):
- Clonal plasma cell & gt; 10% in bone marrow biopsy or (in any amount) in biopsies from other tissues (plasmacytoma)
- Monoclonal protein (Myeloma protein) in both serum and urine (except in case of non-secretory myeloma)
- Evidence of end-organ damage associated with plasma cell disruption (damage to related organs or tissues, commonly referred to as "CRAB" acronym):
- Hyper C alcemia (corrects calcium & gt; 2.75 mmol/l, & gt; 11 mg/dL)
- R enzyme insufficiency caused by myeloma
- A nemia (hemoglobin & lt; 10 g/dl)
- B one lesion (lesion lesion or osteoporosis with compression fracture)
Note: Recurrent infections alone in patients without CRAB features are not sufficient to make a diagnosis of myeloma. Patients who lack CRAB features but have evidence of amyloidosis should be considered amyloidosis and not myeloma. Abnormalities such as crabs are common with many diseases, and it is imperative that these abnormalities are felt directly related to plasma cell-related disorders and any attempts made to exclude other causes of anemia, kidney failure, etc.
- Asymptomatic/burning myeloma:
- Serum M protein & gt; 30 g/l (3 g/dL) or
- Clonal plasma cell & gt; 10% in bone marrow biopsy and
- No organ or tissue damage related to myeloma
- Monochlonal gammopathy with undetermined significance (MGUS):
- Paraprotein serum & lt; 30 g/l (3 g/dL) and
- Clonal plasma cells & lt; 10% in bone marrow biopsy and
- No organ or tissue damage related to myeloma or associated B cell lymphoproliferative disorder
Related conditions include solitary plasmacytoma (plasma single-cell tumor, usually treated with irradiation), plasma dyscrasia cells (where only antibodies produce symptoms, eg, AL amyloidosis), and peripheral neuropathy, organomegaly, endocrineopathy, monoclonal plasma cell disorders, and skin changes.
Staging
- International Staging System
International Staging System (ISS) for myeloma published by International Myeloma Working Group in 2005:
- Stage I:? 2 microglobulin (? 2M) & lt; 3.5 mg/L, albumin> = 3.5 g/dL
- Phase II :? 2M & lt; 3.5 mg/L and albumin & lt; 3.5 g/dL; or? 2M 3.5-5.5 mg/L apart from serum albumin
- Stage III :? 2M> = 5,5Ã, mg/L
Note that the ISS should be used only in patients who meet the diagnostic criteria for myeloma. Patients with MGUS and myeloma asymptomatic having renal dysfunction from unrelated causes such as diabetes or hypertension may have increased? 2M levels of renal dysfunction and can not be considered as myeloma stage III. This is one of the limits of the ISS. It does not really measure the burden of the tumor or its extent unlike the staging systems used in other cancers. This is more of a prognostic index than a true staging system. For this reason, it is recommended that ISS be used in conjunction with the Durie-Salmon Staging System (see below).
- Durie-Salmon staging system
First published in 1975, the Durie-Salmon staging system is still in use. However, one limitation of the Durie-Salmon staging system is the subjectivity in determining the rate of bone disease.
- stage I: all
- Hb & gt; 10 g/dL
- normal calcium
- Skeletal survey: normal or single plasmasitoma or osteoporosis
- Serum paraprotein level & lt; 5 g/dL if IgG, & lt; 3 g/dL if IgA
- Expression of urinary tract chains & lt; 4 g/24 hours
- stage II: meets both I and III criteria
- stage III: one or more
- Hb & lt; 8.5 g/dL
- high calcium & gt; 12 mg/dL
- Skeletal survey: Three or more lytic bone lesions
- Paraprotein serum & gt; 7 g/dL if IgG, & gt; 5 g/dL if IgA
- Light urine chain excrescence & gt; 12 g/24 hours
Stages I, II, and III Durie-Salmon staging systems can be divided into A or B depending on serum creatinine:
- A: serum creatinine & lt; 2 mg/dL (& lt; 177? Mol/L)
- B: serum creatinine & gt; 2 mg/dL (& gt; 177? Mol/L)
Prevention
The risk of multiple myeloma can be reduced by maintaining a normal weight.
Treatment
Treatment for multiple myeloma is focused on therapies that decrease the clonal plasma cell population and consequently reduce the signs and symptoms of the disease. If the disease is completely asymptomatic (ie paraprotein and abnormal bone marrow population but no end-organ damage), as in the asymptomatic ("smoldering") myeloma, treatment is usually delayed, or limited to clinical trials.
In addition to the direct treatment of plasma cell proliferation, bisphosphonates (eg, pamidronate or zoledronic acid) are routinely given to prevent fractures; they have also been observed to have a direct anti-tumor effect even in patients without known skeletal disease. If necessary, red blood cell transfusion or erythropoietin may be used for the management of anemia.
Initial therapy
The initial treatment of multiple myeloma depends on the age and comorbidity of the patient.
Preferable treatments for those under 65 years of age are high-dose chemotherapy, generally with a bortezomib-based regimen, and lenalidomide-dexamethasone. This is followed by an autologous hematopoietic stem cell transplant (ASCT) - a patient's own stem cell transplant. This is not curative, but prolongs overall survival and complete remission. Allogenic stem cell transplantation, transplantation of healthy person stem cells into affected patients, has the potential to heal, but is used in very small percentages of patients (and in relapse settings, not as part of initial treatment). In addition, there is a 5-10% associated mortality rate associated with allogeneic stem cell transplantation.
People over the age of 65 and people with significant concomitant diseases often can not tolerate stem cell transplantation. For these patients, the standard of care is chemotherapy with melphalan and prednisone. Recent studies among these populations showed better results with new chemotherapy regimens, for example, with bortezomib. Treatment with bortezomib, melphalan, and prednisone had an overall survival estimated at 83% at 30 months, lenalidomide plus low dose dexamethasone 82% survived at 2 years and melphalan, prednisone and lenalidomide had 90% survival at 2 years. A head-to-head study comparing this regimen was not done in 2008.
A 2009 review noted "deep vein thrombosis and pulmonary embolism are a major side effect of thalidomide and lenalidomide.Lenalidomide causes more myelosuppression, and thalidomide leads to more sedation The peripheral neuropathy induced by chemotherapy and thrombocytopenia is a major side effect of bortezomib."
Treatment of associated hyperviscosity syndrome may be necessary to prevent neurological symptoms or renal failure.
Maintenance therapy
Most people, including those treated with ASCT, will recur after initial treatment. Treatment therapy using prolonged toxicity treatment is often used to prevent recurrence. A 2017 meta-analysis shows that post-ASCT treatment therapy with lenalidomide improves free survival and overall survival in people at standard risk. The 2012 clinical trials show that people with medium and high risk diseases benefit from a bortezomib-based maintenance regimen.
Relapse
Myeloma's natural history of relapse after treatment. This may be due to tumor heterogeneity. Depending on the patient's condition, previous treatment modalities are used and the duration of remission, the options for recurrent disease include re-treatment with the original agent, use of other agents (such as melphalan, cyclophosphamide, thalidomide or dexamethasone alone or in combination), and second autologous stem cell transplant.
Later in the course of the disease, "treatment resistance" occurs. This may be a reversible effect, and some new treatment modalities may re-sensitize the tumor to standard therapy. For patients with recurrent disease , bortezomib is a recent addition to therapeutic arsenal, primarily as second-line therapy, since 2005. Bortezomib is a proteasome inhibitor. Also, lenalidomide (Revlimid), a less toxic analogous thalidomide, shows promise to treat myeloma. Newly approved thalidomide derivative pomalidomide (Pomalyst in the US) can be used for multiple and refractory myeloma.
In the 21st century, more patients survive longer, as a result of stem cell transplants (with their own or donors) and treatments combining bortezomib (Velcade), dexamethasone and melfalan or cyclophosphamide. This seems to keep the monoclonal peak at a reasonable level. Hope for survival has increased. New treatments are under development.
Kidney failure in multiple myeloma can be acute (reversible) or chronic (irreversible). Acute renal failure is usually lost when the levels of calcium and paraprotein are controlled. Treatment of chronic renal failure depends on the type of renal failure and may involve dialysis.
Several new options are approved for advanced disease management:
- ixazomib - a available orally available proteasome inhibitor shown in combination with lenalidomide and dexamethasone in persons who have received at least one previous therapy;
- panobinostat - an orally available histone deacetylase inhibitor used in combination with bortezomib and dexamethasone in people who have received at least 2 previous chemotherapy regimens, including bortezomib and immunomodulatory agents (such as lenalidomide or pomalidomide);
- carfilzomib - the indicated proteasome inhibitor:
- as a single agent for the treatment of patients with multiple myeloma relapsing or refractory who have received one or more treatment lines;
- in combination with dexamethasone or with dexamethasone lenalidomide for treatment of patients with recurrent or refractory multiple myeloma who have received 1-3 therapy pathways;
- elotuzumab - human monoclonal antibody with immunostimulant against SLAMF7 (also known as CD319). It is FDA approved for the treatment of patients who have received one to three previous treatments (in combination with lenalidomide and dexamethasone);
- daratumumab - a monoclonal antibody to CD38 is indicated for the treatment of patients with multiple myeloma who have received at least three previous therapy lines including proteasome inhibitors and immunomodulatory agents or double refractory agents for proteasome inhibitors and immunomodulatory agents.
Palliative care
Some national cancer treatment guidelines recommend early palliative care for people with multiple myeloma advanced at the time of diagnosis as well as for anyone who has significant symptoms.
Palliative care is appropriate at each stage of multiple myeloma and can be given in conjunction with curative treatment. In addition to overcoming the symptoms of cancer, palliative care helps manage unwanted side effects, such as pain and nausea related treatments.
Prognosis
With high-dose therapy followed by autologous stem cell transplant, mean survival was estimated in 2003 to be about 4.5 years, compared with a median of about 3.5 years with "standard" therapy. Overall the 5-year survival rate is about 35%.
The International Staging System can help predict survival, with average survival (in 2005) of 62 months for stage 1, 45 month disease for stage 2 disease, and 29 months for stage 3 disease.
The prognosis for patients with multiple myeloma, as in other diseases, is not the same for everyone. The mean age of onset is 70 years. Older patients often have other serious illnesses, which affect survival. Younger patients may have longer survival rates.
Genetic testing
Some mieloma centers now use genetic testing, which they call "the gene sequence." By examining DNA, oncologists can determine whether patients at high risk or low risk of cancer return quickly after treatment.
Cytogenetic analysis of myeloma cells can be a prognostic value, with chromosome 13 removal, non-hyperdiploidy and balanced translocation t (4; 14) and t (14; 16) giving a worse prognosis. Cytogenetic abnormalities 11q13 and 6p21 are associated with a better prognosis.
Such prognostic markers are always generated by retrospective analysis, and it is possible that the development of new treatments will increase the prospects for those who are traditionally "at risk" disease.
SNP array karyotyping can detect changes in the number of copies of prognostic significance that may be missed by targeted FISH panels. In MM, the lack of proliferative clones makes conventional informative cytogenetics only ~ 30% of cases.
- Virtual karyotyping identifies chromosomal abnormalities in 98% of MM cases
- del (12p13.31) is an independent negative marker
- amp (5q31.1) is a beneficial marker
- The prognostic effects of amp (5q31.1) over-rides hyperdiploidy and also identifies patients who benefit greatly from high-dose therapy.
Arrange-based karyotyping can not detect balanced translocations, such as t (4; 14) seen at ~ 15% MM. Therefore, FISH for this translocation should also be performed if using the SNP array to detect the change in the number of copies of the genome from the prognostic significance in MM.
Epidemiology
Globally, multiple myeloma affects 488,000 people and results in 101,100 deaths by 2015. This is up from 49,000 in 1990.
United States
In the United States by 2016, there will be about 30,330 new cases and 12,650 deaths. These figures are based on assumptions made using data from 2011, which estimates the prevalence as 83,367 people, the incidence as 6.1 per 100,000 people per year, and deaths of 3.4 per 100,000 people per year.
Multiple myeloma is the second most common blood cancer (10%) after non-Hodgkin's lymphoma. It represents about 1.8% of all new cancers and 2.1% of all cancer deaths.
Multiple myeloma affects men less than women. African Americans and Native Pacific Islands have the highest reported incidence of illness in the United States and Asia. Recent studies have 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 causes of cancer death.
English
Myeloma is the 17th most common cancer in the UK (about 4,800 people diagnosed with the disease in 2011), and it is the 16th most common cause of death (about 2,700 people die in 2012).
History
The alternative name of Kahler's disease is after Otto Kahler.
Other animals
Multiple myeloma affects many other species. The disease has been diagnosed in dogs, cats, and horses.
In dogs, multiple myeloma accounts for about 8% of all haemopoietic tumors. Multiple myeloma occurs in older dogs, and is not specifically associated with men or women. No offspring appear excessively in case reviews have been done. Diagnosis in dogs is usually delayed due to early non-specificity and possible clinical signs. Diagnosis usually involves the study of bone marrow, X-rays, and plasma protein studies. In dogs, protein studies usually reveal an increase in monoclonal gammaglobulin to IgA or IgG in the same incident. In rare cases, elevated globulin is IgM, which is referred to as Waldenström macroglobulinemia. The prognosis for early control and return to good quality of life in dogs is good. 43% of dogs starting with a combination chemotherapy protocol achieve complete remission. Long-term survival is normal, with an average of 540 days reported. The disease eventually relapsed, becoming resistant to the available therapies. Complications of renal failure, sepsis, or pain can cause animal death, often by euthanasia.
See also
References
External links
- Multiple myeloma in Curlie (based on DMOZ)
Source of the article : Wikipedia
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