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Early symptomsThe accumulation of malignant plasma cells can result in tiny cracks or fractures in bones. Bone destructionBone pain, particularly in the backbone, hips, and skull, is often the first symptom of multiple myeloma. Hypercalcemia affects about one-third of multiple myeloma patients.Serum proteinsThe accumulation of M-proteins in the serum (the liquid portion of the blood) may cause additional complications, such as hyperviscosity syndrome, or thickening of the blood (though rare in multiple myeloma patients). DiagnosisBlood and urine testsOften, the original diagnosis of multiple myeloma is made from routine blood tests that are performed for other reasons. Approximately 5% of multiple myeloma cases are not progressing at diagnosis, and may not progress for months or years.
Since multiple myeloma often progresses slowly, and since the treatments can be toxic, the disease may not be treated until M-protein levels in the blood are quite high. However, with very sensitive testing, a few myeloma cells are usually detectable and eventually lead to a recurrence of the disease, in the bone or elsewhere in the body.PreventionThere are no clearly-established risk factors for multiple myeloma and it is possible that a combination of factors interact to cause the disease.
An estimated 16,000 patients were diagnosed with multiple myeloma in 2005, and about 11,300 patients died of their disease in the same year. Multiple myeloma is a neoplasm of malignant plasma cells phenotypically expressing CD38, CD56, and CD138. The natural history of multiple myeloma is one of progressive bone destruction, refractory cytopenias, and end-organ damage in the form of renal and cardiac dysfunction. The clinical manifestations of multiple myeloma can be divided into three categories—plasma cell growth in bone marrow and skeletal disease, immunologic abnormalities, and effects of abnormal paraprotein.
The most common manifesting symptom of multiple myeloma is bone pain, usually involving the spine or chest. Renal dysfunction can have many causes in patients with multiple myeloma and is present in about 50% of patients at diagnosis.
Multiple myeloma should be suspected in older adults presenting with back pain, constitutional symptoms (sweats, weight loss), and elevated total protein levels. Evidence of end-organ damage (hypercalcemia, renal insufficiency, anemia, lytic bone lesions) is required for the diagnosis of symptomatic multiple myeloma. The staging evaluation of patients with multiple myeloma should include diagnostic tests as well as prognostic tests.
Adapted from Jacobson JL, Hussein MA, Barlogie B, et al: A new staging system for multiple myeloma patients based on the Southwest Oncology Group (SWOG) experience. Patients with multiple myeloma occasionally have associated complications that require immediate attention, including hypercalcemia, renal failure, and spinal cord compression. The use of bisphosphonates (pamidronate or zoledronic acid) is recommended for almost all myeloma patients with lytic lesions or significant osteoporosis and normal renal function.
In addition, bisphosphonate therapy has analgesic properties for pain related to lytic lesions and possibly antineoplastic properties, and is effective treatment for hypercalcemia in multiple myeloma patients. Patients with plasma cell dyscrasias, and specifically multiple myeloma, have an increased risk of venous thromboembolic events. A number of response criteria have been used to assess the efficacy of therapy for multiple myeloma.
Although conventional therapy cannot cure multiple myeloma, it can effect a temporary remission. Thalidomide, an oral immunomodulatory drug, is efficacious for patients with relapsed and refractory multiple myeloma. Possible explanations for this finding include the inferiority of total body irradiation as a preparative regimen in multiple myeloma (when compared with high-dose melphalan), and the more intensive standard chemotherapy arm in this study, which consisted of VBMCP therapy (vincristine, carmustine, melphalan, cyclophosphamide, and prednisone in 5-week cycles) for 1 year. More recently, preliminary results of a randomized clinical trial conducted by the Intergroupe Français du Myelome (IFM) have suggested a role for thalidomide maintenance therapy.
Despite effective first-line therapy, all patients with multiple myeloma will experience a progression of their disease.
Multiple myeloma is a plasma cell neoplasm characterized by a monoclonal gammopathy, bone marrow plasmacytosis, and end-organ damage. A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. Maintenance therapy with alternate-day prednisone improves survival in multiple myeloma patients. Criteria for evaluating disease response and progression in patients with multiple myeloma treated by high-dose therapy and haemopoietic stem cell transplantation.
Kyphoplasty in the treatment of osteolytic vertebral compression fractures as a result of multiple myeloma. Phase III clinical trial of thalidomide plus dexamethasone compared with dexamethasone alone in newly diagnosed multiple myeloma: A clinical trial coordinated by the Eastern Cooperative Oncology Group. Pegylated liposomal doxorubicin, vincristine, and dexamethasone provide significant reduction in toxicity compared with doxorubicin, vincristine, and dexamethasone in patients with newly diagnosed multiple myeloma: A phase III multicenter randomized trial.
Zoledronic acid versus pamidronate in the treatment of skeletal metastases in patients with breast cancer or osteolytic lesions of multiple myeloma: A phase III, double-blind, comparative trial. Criteria for the classification of monoclonal gammopathies, multiple myeloma and related disorders: A report of the International Myeloma Working Group.
Pegylated liposomal doxorubicin, vincristine, and dexamethasone provide significant reduction in toxicity compared with doxorubicin, vincristine, and dexamethasone in patients with newly diagnosed multiple myeloma: A Phase III multicenter randomized trial. Similar to leukemias and lymphomas, multiple myeloma falls into the general category of hematologic (blood) cancers.
Diagnosed in an estimated 24,050 people this year, multiple myeloma is a type of blood cancer that starts in plasma cells inside bone marrow and develops when normal plasma cells transform and grow uncontrollably. To fully understand multiple myeloma, it’s important to first gain a general knowledge of bone marrow, lymphocytes and plasma cells (see Figures 1 and 2). While the exact cause of multiple myeloma is unknown, certain factors can raise your risk, including a family history of multiple myeloma, exposure to radiation, obesity, and other plasma cell diseases such as monoclonal gammopathy of undetermined significance.
Studies have also found that most people with multiple myeloma have identifiable genetic mutations in their plasma cells.
Symptoms of the disease vary among patients and depend on the number of myeloma cells in the body and the area of the body where they collect. One common symptom of multiple myeloma is recurrent fevers and infections, especially pneumonia, sinus infections, infections of the kidneys or bladder, skin infections and shingles. Bone pain, especially in the back, ribs and hips, is another common symptom of multiple myeloma. Also ask about pain management right from the start, and continually alert your doctor at the first sign of pain. A medical history of a condition called monoclonal gammopathy of undetermined significance (MGUS) is also a risk factor for multiple myeloma. These particles can block small blood vessels and cause pain and numbness in the toes, fingers, and other extremities during cold weather.Amyloidosis is a rare complication of multiple myeloma. Most patients have stage III multiple myeloma at diagnosis.Prognostic indicatorsPrognostic indicators for multiple myeloma may be used instead of, or in addition to, the staging system described above.

These drugs can slow the progression of bone disease, reduce pain, and help prevent bone fractures.
Multiple myeloma is a disorder of older adults, with a median age at diagnosis of approximately 65 years. Although most back pain often results from bone marrow replacement, discrete lytic lesions, or vertebral compression fractures, spinal cord compression must always be considered and ruled out, especially when back pain is not well explained by routine x-rays.
Anemia in multiple myeloma is multifactorial and is secondary to bone marrow replacement by malignant plasma cells, chronic inflammation, relative erythropoietin deficiency, and vitamin deficiency. Plasma cell leukemia, a condition in which plasma cells comprise greater than 20% of peripheral leukocytes, is typically a terminal stage of multiple myeloma and is associated with short survival. Patients with myeloma often suffer from repeated infections, similar to those seen in patients with reduced levels of immunoglobulins. Antibodies to factor X are occasionally present in patients with multiple myeloma and result in abnormal bleeding. Vertebroplasty and kyphoplasty have resulted in major improvement in regard to diminishing the pain of compression fractures.
Immediate adverse effects of bisphosphonate therapy include flulike symptoms associated with the first infusion and renal dysfunction, which is in part related to the infusion rate. The past decade has witnessed the addition of a number of exciting novel therapeutic agents for relapsed and newly diagnosed myeloma. The landmark study included 399 patients with newly diagnosed multiple myeloma who underwent three or four cycles of VAD chemotherapy. A number of principles are inherent to the treatment of patients with relapsed or refractory multiple myeloma. Correlation of measured myeloma cell mass with presenting clinical features, response to treatment, and survival. As these abnormal cells multiply, they prevent the growth of healthy cells in the bone marrow. In time, the myeloma cells accumulate in bone marrow, solid parts of bone and occasionally in other organs. Multiple myeloma is more common in older adults than in youths, in men than in women, and in African-Americans than in Caucasians.
For example, in about half of those with multiple myeloma, part of one chromosome in the myeloma cells has switched with part of another chromosome.
Some people with multiple myeloma may not have symptoms early in the course of the disease, and doctors may simply monitor the condition until specific symptoms appear. These infections may occur because the overgrowth of myeloma cells suppresses the growth of healthy white blood cells (which fight infections). The pain is caused by bone damage and osteoporosis (thinning of the bone), which can lead to bone fractures; the pain often gets worse at night and with movement.
Pain management works best when it’s done proactively rather than reactively, and ideally, pain should be addressed long before it becomes an emergency.
This type of pain can be treated in several ways, including radiation, drug therapy (pain medications and bone-strengthening bisphosphonates), orthopedic surgeries and procedures, ablation treatments, vertebroplasty (a procedure in which bone cement is injected into collapsed spinal vertebrae), and more. About 3 percent of all people over age 50 have MGUS in the United States, and about 1 percent of them progress to multiple myeloma or lymphoma. Multiple myeloma accounts for approximately 1% of all cancers and 2% of all deaths from cancer. About 80% of individuals with multiple myeloma are anemic due to low red blood cell formation. Since all of the multiple myeloma M-proteins in the blood and urine are identical, electrophoresis of blood and urine from a patient with multiple myeloma shows a large M-protein spike, corresponding to the high concentration of monoclonal Ig.
These patients have stage I blood chemistry but no symptoms.Stage II multiple myeloma fits neither stage I nor stage III. Multiple myeloma is a plasma cell dyscrasia characterized by destructive lytic bone lesions, a plasma cell infiltrate in the bone marrow, and a monoclonal protein in the serum or urine. Males and African Americans have twice the incidence of multiple myeloma as females and whites, respectively.
Overproduction of interleukin-6 (IL-6), an autocrine and paracrine plasma cell growth factor, is believed to be central to the pathogenesis of multiple myeloma. Recombinant human erythropoietin is effective for the treatment of anemia in multiple myeloma. In addition, cast nephropathy (so-called myeloma kidney), amyloidosis, and light chain deposition should be considered when immediately reversible causes are excluded. Alternatively, patients with asymptomatic (smoldering) multiple myeloma may be followed without specific therapy until clear evidence of progression is noted.
Adverse laboratory prognostic variables in multiple myeloma include high serum β2-microglobulin, high serum lactate dehydrogenase, low serum albumin, and high creatinine and C-reactive protein levels.
But because myeloma cells are all the same, they produce too much of the same antibody, which accumulates in the blood and urine and can lead to kidney and other organ damage. Also, because of a reduction in red blood cells, multiple myeloma can cause anemia with symptoms of fatigue, weakness and shortness of breath. If the myeloma affects the spine, bones that make up the spine (vertebrae) can collapse, causing severe pain. As a patient, you are entitled to have a doctor totally committed to relieving any pain you may experience, so if you don’t already have someone like that on your multidisciplinary health care team, ask for a referral. Multiple myeloma is a disease in which malignant plasma cells spread through the bone marrow and hard outer portions of the large bones of the body. Specific genetic disorders and environmental exposures have not been clearly linked to the risk of multiple myeloma. Characteristic lesions of multiple myeloma are lytic lesions (rounded, punched-out areas of bone) found most commonly in vertebral bodies, the skull, ribs, humerus, and femur (Fig.
Therapy directed at the malignant plasma cell clone often treats the myeloma kidney as well.
Baseline dental evaluation as well as prompt evaluation of jaw symptoms is recommended for patients receiving these agents.
Research is ongoing to determine the precise role these changes in DNA play in the cause of multiple myeloma. People with multiple myeloma may also bruise and bleed easily when they lack sufficient blood platelets. Fractured bones or weak or collapsed spinal bones, in turn, may place unusual pressure on nearby nerves, resulting in nerve pain, burning, or numbness and muscle weakness. Laboratory studies suggest that bisphosphonates may kill or inhibit the growth of multiple myeloma cells. The majority of people with multiple myeloma have these lesions when they’re diagnosed with the disease. Eventually, multiple soft spots or holes, called osteolytic lesions, form in the bones.Bone marrow is the spongy tissue within the bones.

Proteins produced by myeloma cells also may damage nerves.Calcium from the destroyed bone enters the blood and urine, causing hypercalcemia, a medical condition in which abnormally high concentrations of calcium compounds exist in the bloodstream.
Pamidronate is the most common bisphosphonate for treating multiple myeloma.The drug thalidomide appears to have several anti-myeloma activities.
Cytogenetic abnormalities by metaphase cytogenetics are identified in approximately 50% of multiple myeloma patients.
If 10% to 30% of the cells are plasma cells, multiple myeloma is the usual diagnosis.X rays are used to detect osteoporosis, osteolytic lesions, and fractures.
Thalidomide affects the immune system in various ways and it appears to inhibit myeloma cells, both directly and indirectly.
Other chemotherapy drugs, including cyclophosphamide, carmustine, doxorubicin, vincristine, and chlorambucil, may be used as well.Multiple myeloma usually recurs within a year after the end of chemotherapy. Accordingly, skeletal surveys are used in the initial evaluation and follow-up of patients with multiple myeloma. Hypercalcemia in patients with multiple myeloma is secondary to bone turnover and is treated with bisphosphonate therapy, which is also useful for decreasing pain from lytic lesions and in skeleton-related events and may have an antimyeloma effect.
Over a period of years, about 16% to 20% of those with MGUS will develop multiple myeloma or a related cancer called malignant lymphoma.Occasionally, only a single plasmacytoma develops, either in the bone marrow (isolated plasmacytoma of the bone) or other tissues or organs (extramedullary plasmacytoma).
Some individuals with solitary plasmacytoma may develop multiple myeloma.Clinical stagesThe Durie-Salmon system is used to stage multiple myeloma. In an autologous transplant, the patient's bone marrow stem cells or peripheral blood stem cells (immature bone marrow cells found in the blood) are collected, treated with drugs to kill any myeloma cells, and frozen prior to chemotherapy. They produce large amounts of identical antibody that are specific for the antigen.Malignant plasma cellsMultiple myeloma begins when the genetic material (DNA) is damaged during the development of a stem cell into a B-cell in the bone marrow. A growth factor, called interleukin-6, promotes uncontrolled growth of these myeloma cells in the bone marrow and prevents their natural death. Whereas normal bone marrow contains less than 5% plasma cells, bone marrow of an individual with multiple myeloma contains over 10% plasma cells.In most cases of multiple myeloma, the malignant plasma cells all make an identical Ig. The blood cells are transfused back into the patient, along with a plasma substitute or donated plasma.Multiple myeloma may be treated with highenergy x rays directed at a specific region of the body. However, interferon may have toxic effects in older individuals with multiple myeloma.Once multiple myeloma is in remission, calcium and vitamin D supplements can improve bone density. All of the paraproteins from any one individual are monoclonal (identical) because the myeloma cells are identical clones of a single plasma cell. Individuals with multiple myeloma must drink large amounts of fluid to counter the effects of hyperviscous blood.PrognosisThe prognosis for individuals with MGUS or solitary plasmacytoma is very good.
However, approximately 15% of all patients with multiple myeloma die within three months of diagnosis. Thus, multiple myeloma depresses the immune system.In about 75% of multiple myeloma cases, the malignant plasma cells also produce monoclonal light chains, or incomplete Igs. Called also plasma cell myeloma.Diagnostic procedures to confirm suspected multiple myeloma include blood analyses, quantitative immunologic assays of serum and urine, urinalysis, bone marrow aspiration and biopsy, and skeletal x-rays.
Approximately 1% of multiple myelomas are called nonsecretors because they do not produce any abnormal Ig.Osteolytic lesionsAbout 70% of individuals with multiple myeloma have soft spots or lesions in their bones. Treatment of multiple myeloma involves chemotherapy and radiation to relieve pain and manage the acute lesions of the spinal column.
Individuals diagnosed with multiple myeloma who show no symptoms do not usually receive treatment.Patient Care.
The deletion of this chromosome, along with high beta 2-microglobulin, leads to a poor prognosis.With treatment, multiple myeloma may go into complete remission.
Major problems presented by the patient with multiple myeloma are related to anemia, hypercalcemia, bone pain and pathologic fractures, and emotional distress created by trying to cope with the day-to-day physiologic and emotional aspects associated with the diagnosis of a malignant disease. The more common complications to be avoided are infection, renal failure, and the sequelae of spinal cord compression.Transfusions with packed red blood cells can help alleviate and minimize some of the more severe symptoms of anemia. Osteoporosis, or widespread bone weakness, may develop.There are more than 40,000 multiple myeloma patients in the United States. Other problems are related to the administration of highly toxic antineoplastic drugs.Multiple myeloma. Multiple myeloma is one of the leading causes of cancer deaths among African Americans.In Western industrialized countries, approximately four people in 100,000 develop multiple myeloma. The incidence of multiple myeloma among African Americans is 9.5 per 100,000, about twice that of Caucasians.
The offspring and siblings of individuals with multiple myeloma are at a slightly increased risk for the disease.At diagnosis, the average age of a multiple myeloma patient is 68 to 70.
Although the average age at onset is decreasing, most multiple myelomas still occur in people over 40. This cancer is somewhat more prevalent in men than in women.Causes and symptomsAssociationsThe cause of multiple myeloma has not been determined. The symptoms caused by these lesions are typically weakness, incoordination, paresthesias, speech disturbances, and visual disturbances, particularly diplopia.
More specific signs and symptoms depend on the location of the lesions and the severity and destructiveness of the inflammatory and sclerotic processes.The course of the disease is usually prolonged, with remissions and relapses over many years. Brief exacerbations, even with acute and severe symptoms, are thought to be the result of a transient inflammatory depression of neural transmission. The onset of symptoms most often occurs between the ages of 20 and 40 years, and the disease affects both sexes about equally.The cause of multiple sclerosis is unknown. Others believe there is an antigen or environmental trigger for the disease.The diagnosis of multiple sclerosis is difficult because of the wide variety of possible clinical manifestations and the resemblance they bear to other neurological disorders.
There is no definitive diagnostic test for the condition, but persons with objectively measured abnormalities of the central nervous system, a history of exacerbation and remission of symptoms, and demonstrable delayed blink reflex and evoked visual response are diagnosed as having either possible or probable multiple sclerosis. With time and progressive worsening of symptoms the diagnosis can become definite.Treatment.
Multiple sclerosis has an impact on physical activity and life style, role, and interpersonal relationships; therefore, vocational guidance, counseling, and group therapy are helpful.
Stress due to trauma, infection, overexertion, surgery, or emotional upset can aggravate the condition and precipitate a flare-up of symptoms. Research support is strong that these medications reduce the frequency and severity of relapses.Many multiple sclerosis patients and their families receive valuable support and encouragement from communication with others coping with the condition. A local chapter of the National Multiple Sclerosis Society is within reach of most persons in the United States. It's a condition that resembles myeloma but is much more widespread and by itself isn't considered malignant.

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