Anatomy and physiology related to multiple myeloma Multiple myeloma is a cancer of the plasma cells.

Plasma cells are found in the bone marrow and other tissues and organs. They are a type of white blood cell that make antibodies. Multiple myeloma is considered a hematological or blood cancer because it affects blood cells. Under normal circumstances, plasma cells are found in bone marrow, where blood cells are made. Normal bone marrow contains few plasma cells. A person with multiple myeloma often has many abnormal plasma cells (myeloma cells) in the bone marrow. The myeloma cells can form tumours in bones called plasmacytomas. If there is only one tumour of myeloma cells in the bone, it is called a solitary plasmacytoma. When many plasmacytomas are found in the bones, the condition is called multiple myeloma. Plasmacytomas can also form outside of the bones and are called extramedullary plasmacytomas. Structure Bone marrow is the soft, spongy substance in the centre of the bone where blood cells are made. In adults, the most active bone marrow is found in the pelvic and shoulder bones, spine (vertebrae), ribs, breastbone and skull. Plasmacytomas usually develop in the areas where bone marrow is active. Blood is made up of liquid (called plasma) and solid cells. Plasma is made up of water and chemicals, such as proteins, minerals and vitamins, that are dissolved in the water. All our blood cells develop from stem cells. The process of blood cell development is called hematopoiesis. In the earliest stage of cell development, stem cells begin to develop along either the lymphoid cell line or the myeloid cell line. In both cell lines, the stem cells become blasts, which are still immature cells. During the last stage of cell development, the blasts mature into 3 types of blood cells.

Platelets help the blood to clot when a blood vessel is damaged. . They can also kill viruses and cancer cells. White blood cells The immune system is the body's natural defence against infection. White blood cells help prevent and fight infection by destroying bacteria.Function Each of the 3 types of blood cells in the plasma has a specific role:    Red blood cells carry oxygen from the lungs to the rest of the body and return carbon dioxide to the lungs. White blood cells are an important part of the immune system. viruses and other foreign cells or substances.  o lymphocytes T cells recognize antigens and activate the B cells. Different types of white blood cells work in different ways to protect the body from infection.

IgM. they turn into plasma cells. or immunoglobulins. cancer cells and other foreign invaders. such as bacteria. There are 2 light . viruses or other foreign substances. The myeloma cells can collect in the bone marrow and crowd out the normal blood cells so they can’t work properly. which produce antibodies to fight infection. a plasma cell makes a new antibody. There are 5 types of immunoglobulins – IgG. When B cells mature. IgD and IgE. Basophils play a role in certain allergic reactions. plasma cells make up about 1% of the cells in bone marrow. are special proteins that fight infection and defend the body against harmful foreign invaders. antibodies and plasma cells Antigens are located on the surface of bacteria. They begin to make many abnormal plasma cells (myeloma cells). Immunoglobulins Immunoglobulins (Ig) are protein molecules called antibodies produced by plasma cells. Normally. including cancer cells. B cells are damaged and do not work properly. When the immune system identifies a new antigen. Antigens. Multiple myeloma starts in B cells. Natural killer (NK) cells attack any foreign cells. Antibodies. Immunoglobulins are made up of 4 parts called chains. Neutrophils and monocytes fight infection by ingesting or engulfing foreign cells. Antibodies are specific to a particular antigen. An antigen triggers plasma cells (B cells) to produce antibodies. In multiple myeloma.o o    B cells develop into plasma cells. In people with multiple myeloma. Once plasma cells respond to an antigen. viruses. They attack and destroy certain parasitic organisms. They circulate in the blood and attach to specific antigens on the surface of bacteria. abnormal plasma cells make up 10%–30% of the cells in the bone marrow. IgA. Eosinophils help control inflammation and allergic reactions. they will only make antibodies for that antigen.

 o o  o o o o o light chains kappa lambda heavy chains IgG IgA IgM IgD IgE When damaged B cells develop into abnormal plasma cells (myeloma cells). Bone destruction . Each of the 5 types of immunoglobulins is named after the type of heavy chain that it contains. The light chains that are not attached to heavy chains are called Bence Jones proteins. Multiple myeloma and other plasma cell cancers are classified by the type of immunoglobulin produced by the myeloma cells and by the type of light or heavy chain. Their presence indicates that there is a problem with the plasma cells. The 4 chains are attached to each other by special chemical bonds. M-proteins can be measured in the blood and urine. This monoclonal immunoglobulin is also called an M-protein.chains and 2 heavy chains. they make large amounts of one type of immunoglobulin (called a monoclonal immunoglobulin) and release it into the blood. Sometimes the myeloma cells do not release immunoglobulin properly and only release the light chains into the blood.

it helps to understand the anatomy and composition of blood. This is because they release chemicals called cytokines that cause other cells to dissolve bone. These weakened areas of the bone may cause it to break under normal stresses like walking. can be seen on an x-ray as dark circular spots in bones. . called osteolytic lesions. Thinning of the bone can also lead to osteoporosis.cancer. These areas of weakness. lifting and coughing. Read more: http://www. The collection of myeloma cells can start to weaken and thin the bone. Osteolytic lesions may mean a plasmacytoma or other disease of the bone is present. Cytokines also stimulate the growth of more myeloma cells and disrupt their normal life cycle. Blood is a circulating tissue that carries nourishment and oxygen to the cells and Multiple Myeloma Anatomy To better understand multiple myeloma.Myeloma cells can damage the bone when they collect in the bone marrow.

Normal ranges for the total number of red blood cells in adults are:   4. cancer) 0. fungal & TBinfections. These values are reported as a percentage of the total number of cells.11. Cell Type Neutrophils Bands Lymphocytes Monocytes Basophils Eosinophils % Of Total WBC's 47% to 77% (elevated in infection.500 . some cancers.000 (per cubic millimeter).6-6. This can result in poorexercise tolerance and fatigue.3% to 7% (elevated in . There are several types of white cells (leukocytes) present in the blood. and hypothyroidism) 0. A white blood cell differential reports the percentages of the different types of white blood cells that comprise the total white blood cell count.2 million per cubic millimeter (males) 4. Normal total ranges for white blood cells are: 4. lupus. inflammation.4 million per cubic millimeter (females) White Blood Cells White blood cells are an important part of the immune system.Blood is composed of 3 cell types that are suspended in a protein-rich fluid called plasma:    Red blood cells (erythrocytes) White blood cells (leukocytes) Platelets (thrombocytes) Red Blood Cells Red blood cells contain hemoglobin. A decrease in the number of red blood cells reduces the amount of oxygen that can be carried by the bloodstream.3% to 2% (elevated in some leukemias.5% to 10% (elevated in some viral. These cells mainly function to fight infection. Slightly higher counts are normal in children.2-5. andstress) 0% to 3% (elevated in some cases of bacterial infection) 16% to 43% (elevated in some cases of viral infection and some leukemias) 0. which is the molecule that carries oxygen to the tissues.

with each other. carfilzomib (Kyprolis). these agents are used in combination with dexamethasone. Stem cell transplantation may not be an option for many people because of advanced age. A platelet count: 150. MULTIPLE MYELOMA OVERVIEW The treatment of multiple myeloma (MM) is complex because of rapid advances in stem cell transplantation. They play an essential role in the blood clotting system. most people go through many treatment regimens during the course of their illness. or with standard chemotherapy agents. Such transplants.  . In most cases. lenalidomide (Revlimid). Stem cell transplantation — Stem cell transplantation can be done using one's own stem cells (autologous) or using cells from a close relative or matched unrelated donor (allogeneic).000 per cubic millimeter is considered a normal range.some allergies.) TREATMENT ISSUES Types of treatment — There are four main types of treatment:    Chemotherapy — In most people. The symptoms. Newer Drugs — Drugs such as thalidomide (Thalomid). The main options for therapy include:     Standard chemotherapy drugs such as melphalan (Alkeran). Corticosteroids — Corticosteroids include dexamethasone (Decadron) or prednisone. cyclophosphamide (Cytoxan). autoimmune disease) Platelets Platelets are the smallest of the blood cells. This topic review discusses the treatment of multiple myeloma.Hodgkin's disease. bortezomib (Velcade). chemotherapy leads to complete remission. Doxorubicin (Adriamycin) and liposomal doxorubicin (Doxil) Newer drugs such as thalidomide (Thalomid). medications. lenalidomide (Revlimid). presence of other serious illness. (See "Patient information: Multiple myeloma symptoms. diagnosis. cancer. both in newly diagnosed patients and in patients with advanced disease who have failed chemotherapy or transplantation. bortezomib (Velcade). diagnosis. Because current therapy is rarely curative. leukemia.000-400. chemotherapy partially controls multiple myeloma. and pomalidomide (Pomalyst) Corticosteroids such as prednisone or dexamethasone (Decadron) Stem cell (bone marrow) transplantation Each option needs to be weighed carefully. and pomalidomide (Pomalyst) have emerged as important options for treatment of myeloma. carfilzomib (Kyprolis). which have led to improved survival for patients with multiple myeloma over the past thirty years [1]. rarely. and staging (Beyond the Basics)". or other physical limitations (see 'Stem cell transplantation' below). most transplants performed are of the autologous kind. In multiple myeloma. and staging of multiple myeloma are discussed separately. and better supportive care.

decisions are made on a case-by-case basis based upon a person's health and vary across institutions. However. and staging (Beyond the Basics)". They can be done as initial therapy in newly diagnosed patients or at the time of relapse.) . High versus standard risk multiple myeloma is discussed separately. a small percentage of patients with MGUS will eventually develop full-blown myeloma.0 mg/dL (an elevated bilirubin level indicates that the liver may not tolerate the high dose chemotherapy required before transplantation) Serum creatinine >2. age. or standard risk multiple myeloma [2]. stem cell transplantation for multiple myeloma is offered primarily to patients less than 65 years of age. Eligibility varies across countries and across institutions. not everyone with multiple myeloma is a candidate for stem cell transplantation. ability to undergo stem cell transplantation in the future and disease characteristics that denote high. (See "Patient information: Multiple myeloma symptoms. do not require treatment. In the United States. In most centers in the United States. a strict age-limit is not used. have been shown to prolong life in selected patients. treatment with one or more of the options discussed above is recommended for almost all patients. section on 'Risk stratification'. in selected patients more than one transplant may be recommended to adequately control the disease. Is stem cell transplantation an option? — Because of the risk of toxic and even fatal complications related to stem cell transplantation. the decision regarding transplant eligibility should be made by the patient and physician after discussing the potential risks. diagnosis. Individuals with a related condition. once symptoms develop. these factors are guidelines. Sometimes. called monoclonal gammopathy of undetermined significance (MGUS). Autologous transplants for multiple myeloma are very safe in centers with experience in the procedure. Instead. patients with multiple myeloma who have one or more of the following factors are NOT considered eligible for transplantation:    Age >77 years Direct bilirubin >2. those with poor kidney function may not tolerate high dose chemotherapy) Eastern Cooperative Oncology Group (ECOG) performance status 3 or 4 unless due to bone pain (table 1) New York Heart Association functional status Class III or IV (table 2)   However. and the needs and wishes of the patient. In most European countries. benefits. intermediate. TREATMENT OF NEWLY DIAGNOSED MULTIPLE MYELOMA The initial choice of chemotherapy depends upon the patient's health. Individuals with early myeloma who have no symptoms (often called smoldering myeloma) may be advised to wait months to years before considering chemotherapy. When to start treatment? — Multiple myeloma can remain stable for prolonged periods of time. although long-term follow-up is needed.5 mg/dL (221 µmol/liter) unless on chronic stable dialysis (creatinine is a reflection of kidney function.although not curative.

prednisone. dexamethasone (VTD) is preferred.    Melphalan is a chemotherapy drug that functions to kill tumor cells Prednisone is a steroid that functions to kill tumor cells Thalidomide may work to slow the growth of new blood vessels to a tumor and may slow or stop the growth of tumor cells. Most experts recommend enrolling in a clinical trial (see 'Clinical trials' below). If a person is not a candidate for stem cell transplantation (because of underlying medical problems. If later stem cell transplantation is a possibility. or poor health). In such situations. bortezomib melphalan prednisone (VMP). Melphalan prednisone thalidomide (MPT) chemotherapy — The combination of melphalan. stem cells should be collected before melphalan is given because this drug can cause longlasting damage to stem cells. age. dexamethasone (VCD). and thalidomide has been shown to be one of the most effective treatments of multiple myeloma for people who are not planning to undergo stem cell transplantation. a regimen that includes bortezomib.  Melphalan is not usually recommended for people who have kidney failure. lenalidomide.   Standard or intermediate risk multiple myeloma treatment options — People who have standard or intermediate risk multiple myeloma and who develop symptoms are usually treated with one of the following regimens:  If a person is a candidate for stem cell transplantation. Thalidomide is absolutely UNSAFE (contraindicated) for pregnant women. cyclophosphamide. a treatment regimen that includes bortezomib (Velcade) such a bortezomib.bortezomib/dexamethasone. For patients who are not willing or able to participate in a clinical trial:  If a person is a candidate for stem cell transplantation. thalidomide. dexamethasone (VCD) or bortezomib. and bortezomib (VMP) or bortezomib. thalidomide/dexamethasone.High risk multiple myeloma treatment options — The best treatment option for patients with high risk multiple myeloma is not clear. stem cell transplantation either early or later in the treatment course should be considered. chemotherapy is usually recommended as initial therapy. The goal of therapy in high risk myeloma is to achieve and maintain a complete response as much as possible. such as lenalidomide plus dexamethasone (Rd) or bortezomib. age. or poor health). prednisone. After initial therapy (usually about four months). . dexamethasone (VCD). These treatments are less likely to interfere with later collection of stem cells compared with melphalan.) If a person is not a candidate for stem cell transplantation (because of underlying medical problems. several studies have suggested that using a regimen that includes bortezomib can improve survival in certain subsets of patients with high risk multiple myeloma. such as melphalan. or bortezomib. treatment usually consists of regimens such as melphalan prednisone thalidomide (MPT). cyclophosphamide. cyclophosphamide. treatment usually consists of a regimen that does not contain melphalan. (See 'Lenalidomide' below. or lenalidomide plus low dose dexamethasone (Rd). dexamethasone (VRD) is recommended as initial therapy.

However. Both medications are taken as a pill. periodic blood tests are needed to ensure that an individual has adequate levels of white blood cells (cells that fight infection) and platelets (cells important for clotting). it is absolutely unsafe(contraindicated) for pregnant women. some physicians recommend maintenance chemotherapy for people with high risk multiple myeloma (see 'High risk multiple myeloma treatment options' above). It is also especially useful in people with kidney failure and those with highrisk multiple myeloma. Thalidomide is taken every day until the 12 cycles are completed. Treatment-related infections — There is an increased risk of infection during the first two months of chemotherapy or immune modulating therapy. an anticoagulant (eg. People with standard risk multiple myeloma do not usually require additional chemotherapy during the plateau phase. However. vaccination against influenza and pneumonia is strongly recommended before starting chemotherapy. although some people require additional cycles to reach the plateau phase. A "response" to chemotherapy is defined as a 50 percent reduction in blood and urine levels of the abnormal M protein and an improvement of symptoms. The combination of lenalidomide with dexamethasone increases the chance of developing blood clots. lenalidomide is taken for 21 of 28 days. other centers do not routinely recommend preventive antibiotics. they limit the ability to administer chemotherapy. Thalidomide (Thalomid) plus dexamethasone is an alternative to lenalidomide plus dexamethasone. The average survival among individuals treated with MPT is four years. (See "Patient information: Adult vaccines (Beyond the Basics)". daily antibiotics are given during the first two months of chemotherapy to reduce the risk or severity of infections. usually on days one through four every six weeks. it typically lasts six months or longer. In some centers. usually in combination with dexamethasone. in many cases. Bortezomib is given intravenously or subcutaneously. . This combination is one of the preferred initial treatment for people with multiple myeloma who are planning to have stem cell transplantation. and its main side effects are low blood counts and nerve damage. Lenalidomide has the potential to cause severe birth defects. In all cases. aspirin or warfarin) is usually recommended to reduce this risk. a total of 12 cycles is usually recommended. The plateau phase is reached when the myeloma becomes stable and shows no signs of progressing. Lenalidomide — Lenalidomide (Revlimid) is an immune-modulating drug that is effective in the initial treatment of multiple myeloma. It may take 6 to 12 months or even longer for blood tests to reflect the full effects of this chemotherapy on multiple myeloma. which is taken once per week. The dose of melphalan must be adjusted based on these findings. along with dexamethasone. The risks of thalidomide are similar to those of lenalidomide. During MPT chemotherapy. Although this phase is usually temporary.Melphalan and prednisone are taken by mouth. The plateau phase occurs in about one half of individuals after chemotherapy. Bortezomib — Bortezomib (Velcade) is a medication that is effective in treating patients with multiple myeloma and other tumors.) Plateau phase — Chemotherapy is usually continued until multiple myeloma enters a stable (plateau) phase. although it may not be as effective and may have more toxic side effects. As many as one-third of these infections are fatal and. Achieving this phase usually requires at least six cycles of treatment. Each 6 week interval is called a cycle.

this is called delayed transplantation. and stored for later use. This type of transplantation carries very high risks and is not recommended for most individuals with multiple myeloma. Autologous stem cell transplantation is not recommended for individuals with smoldering myeloma. prolongs survival. called Plerixafor. which can be fatal. Single versus double autologous transplantation — Double autologous transplantation (two consecutive autologous transplantations) may be more effective than single autologous transplantation if . this procedure can be done on an outpatient basis. may be added to help with collection. then the previously collected stem cells are thawed and returned to the patient.  Transplantation. and. The high-dose chemotherapy given before transplantation usually fails to kill all of the plasma cells. After an individual recovers from the stem cell collection.STEM CELL TRANSPLANTATION Stem cell transplantation is a treatment option for some individuals with multiple myeloma. Such treatment also puts the patient at risk for serious infections and bleeding. autologous stem cell transplantation is appropriate for up to 50 percent of people with multiple myeloma. Stem cells are then collected from the blood. However. Syngeneic transplantation: the stem cells or bone marrow are obtained from an identical twin of the individual. based on the source of the stem cells:   Autologous transplantation: the stem cells are obtained from the individual with multiple myeloma. Procedure — After initial therapy with a regimen such as lenalidomide/dexamethasone or bortezomib. he or she is given high-dose chemotherapy with melphalan (or similar drugs) to kill as many of the malignant plasma cells as possible. There are three types of transplantation. cyclophosphamide. high doses of melphalan (or similar drugs) are given. Alternatively. dexamethasone (VCD) for three to four months. cures multiple myeloma. and the previously collected stem cells are returned to the patient. and the stem cells are thawed and returned to the patient. In about one-half of patients. High-dose chemotherapy is then given to kill as many plasma cells as possible. leads to a remission. allowing the condition to relapse after transplantation. This is the type of transplantation that is most commonly recommended. after stem cell collection. infrequently. (See "Patient information: Bone marrow transplantation (stem cell transplantation) (Beyond the Basics)". transplantation has several limitations. when successful. This is the optimal form of transplantation. At present. At the time of relapse. an individual is given granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF) to stimulate the production of stem cells. Allogeneic transplantation: the stem cells or bone marrow are obtained from a donor with a tissue type matching that of the patient. although few people with multiple myeloma have an identical twin who can serve as a donor. stem cells are collected and frozen for later use. During this procedure. If there are not sufficient numbers of stem cells in the blood after G-CSF or GM-CSF. Stem cells obtained from the blood are preferred to stem cells from the bone marrow because blood stem cells take up residence in tissues more quickly and are less likely to be contaminated with cancerous plasma cells. frozen. another agent. an individual may be given standard chemotherapy to achieve a plateau phase.) Autologous stem cell transplantation — Autologous stem cell transplantation refers to transplantation with a person's own stem cells.

Remission after transplantation — The strict definition of remission requires that there are no signs or symptoms of multiple myeloma and that highly sensitive tests cannot detect any abnormal plasma cells. Effectiveness — About 1 percent of individuals die from complications related to autologous transplantation. For individuals who have an identical twin. such as zoledronic acid (Zometa) or pamidronate (Aredia). treatment with drugs that act against bone loss. Impaired kidney function — Kidney function becomes impaired in about one half of individuals with multiple myeloma. Other treatments commonly used for multiple myeloma. 50 months. and is associated with 12-month longer survival compared to chemotherapy alone (approximately 57 versus 44 months) [3]. allogeneic transplantation is seldom used for the treatment of myeloma. Primarily because of this toxicity and the lack of clear benefit. The likelihood of a good response to transplantation is somewhat lower for older adults than for younger adults. although the effects of age on survival after transplantation are not completely clear. and graft-versus-host disease. The second transplantation is usually performed within six months of the first. on average. it is generally not recommended for individuals over the age of 70. a class of drugs called bisphosphonates. The treatment of impaired kidney function is aimed at the specific underlying cause. autologous stem cell transplantation is more likely to produce a response. and lenalidomide. However. this procedure may be an option for some people over age 70 who are otherwise healthy. This is because it is often difficult to collect a sufficient number of healthy stem cells for transplantation. lasting. may be recommended. compared with chemotherapy alone. Individuals with MM should remain as active as possible because physical activity helps counter bone loss.the first transplant has not produced a complete or near complete response. such as infection. are safe to take before stem cell transplantation. High blood calcium levels — High blood calcium levels develop as bone is lost. This type of remission occurs in about 4 percent of individuals after autologous transplantation. 51 percent have a complete response. TREATMENT OF MULTIPLE MYELOMA COMPLICATIONS Multiple myeloma can cause a variety of complications. this treatment option is more effective than either autologous or allogeneic transplantation. approximately 25 percent of individuals who undergo allogeneic transplantation die from transplant-related complications. Unfortunately. If this treatment is not effective. Among individuals undergoing double transplantation. . However. One study has shown that double transplantation improves long-term survival relative to single transplantation with the greatest benefit seen in patients who have not achieved an excellent response with the first transplant. including thalidomide. bortezomib. Syngeneic transplantation — A syngeneic transplantation refers to a transplantation between identical twins. Role of age and stage of myeloma — Because autologous stem cell transplantation has serious side effects. some of which are life-threatening. lung inflammation. Importance of prior treatment — Autologous transplantation is not recommended for people who have received prolonged chemotherapy with alkylating drugs (such as melphalan). The treatment of high blood calcium levels usually includes the use of intravenous fluids and prednisone. Allogeneic bone marrow transplantation — Allogeneic transplantation requires bone marrow or stem cells from a donor with a matching tissue type.

a substance that stimulates the production of red blood cells. All individuals with multiple myeloma should receive the pneumococcal vaccine (which reduces the likelihood of pneumonia) and the influenza vaccine (which reduces the likelihood of flu). with careful avoidance of injury. require prompt treatment with antibiotics. Aleve) because these drugs might worsen kidney function. numbness. a waste product from the increased turnover of the malignant plasma cells. radiation. Initial treatment may consist of radiation and dexamethasone (a steroid) to reduce swelling around the spinal cord. can promote bone strength in individuals with multiple myeloma. Daily use of the antibiotic trimethoprim-sulfamethoxazole (Bactrim) can help prevent infections. Therefore. or tingling in the legs. this treatment is continued for approximately two years. patients should avoid such procedures. These medications may affect kidney function. prednisone (a steroid that can indirectly lower blood calcium levels). such as paralysis. and allopurinol. Accordingly. surgery is needed to relieve pressure on the spinal cord. The bone pain associated with multiple myeloma can be controlled with chemotherapy. or new problems with control over their bladder or bowel (incontinence). Advanced degrees of kidney failure are usually not reversible even if the multiple myeloma later responds to treatment. Patients are advised to stay well-hydrated and should drink enough fluid to produce three liters of urine daily if they have Bence Jones proteinuria (increased light chains in the urine). bisphosphonates reduce the risk of fractures and reduce bone pain. Anemia — Anemia (low red blood cell count) that is causing symptoms may require blood transfusions or treatment with erythropoietin (EPO). a drug that can lower blood levels of uric acid. Individuals who get frequent infections may be advised to take penicillin daily or rarely to have periodic intravenous infusions of gamma globulin. Motrin. the treatment options include hemodialysis or peritoneal dialysis. such as Advil. if these measures are not effective. This treatment effectively . If impaired kidney function has progressed to kidney failure. it may also include dialysis (a type of blood filtration used for kidney failure).) Bone pain and fractures — Physical activity. (See "Patient information: Dialysis or kidney transplantation — which is right for me? (Beyond the Basics)". Bisphosphonates are usually given by intravenous infusion every four weeks. may be associated with infection or destruction of the jaw (osteonecrosis) in patients treated with intravenous bisphosphonates. often indicated by the presence of fever.Treatment usually includes intravenous fluids.) Infection — Bacterial infections. if possible. bisphosphonates are recommended for all individuals who have early signs of bone erosions on x-rays. such as root canal or extraction of teeth. weakness. any needed dental procedures should be performed before these agents are started. They should also avoid using any nonsteroidal anti-inflammatory drugs (NSAIDs. and bone strengthening drugs such as zoledronic acid (Zometa) or pamidronate (Aredia) (commonly referred to as bisphosphonates) that can also reduce the likelihood of fractures. analgesics (pain relieving drugs). Dental procedures. Erythropoietin is usually given by injection one to three times per week. Patients should call their doctor immediately if they have severe back pain. which can damage the kidneys. Spinal cord compression — Spinal cord compression is a medical emergency that requires prompt treatment to prevent irreversible damage. In individuals who have early signs of bone erosion. while taking these agents. which should be monitored on a regular basis to avoid this complication. (See "Patient information: Influenza symptoms and treatment (Beyond the Basics)".

TREATMENT OF RELAPSED OR REFRACTORY MULTIPLE MYELOMA Almost all patients with multiple myeloma eventually relapse. and/or standard chemotherapy drugs such as melphalan or cyclophosphamide. given with steroids. he or she may still respond to autologous stem cell transplantation. Refractory multiple myeloma is more difficult to treat. a type of blood filtration that removes the excess monoclonal proteins responsible for the increased viscosity. or pomalidomide.  Relapses occurring more than six months after completing chemotherapy are often treated by resuming the initial chemotherapy. form the major treatment options for relapsed or resistant disease. lenalidomide. Thickening of the blood — Thickening of the blood (called hyperviscosity syndrome) rarely occurs in individuals with multiple myeloma.  . improves symptoms. Said another way. This complication is treated with plasmapheresis. This condition can occur during initial chemotherapy or during chemotherapy given after a relapse. Most individuals will again have a response to chemotherapy when it is given a second time. The lack of response to initial induction chemotherapy does not always mean that the person will not have a good response to autologous stem cell transplantation. and a modest percentage are resistant to initial treatment. although the response is usually shorter and smaller than the original response.increases levels of hemoglobin (the protein in red blood cells that helps carry oxygen to the tissues). Thalidomide. Selected patients can consider autologous stem cell transplantation. if a person does not respond to induction chemotherapy. carfilzomib. and reduces the need for blood transfusion. Multiple myeloma that responds poorly or not at all to melphalan-prednisone thalidomide or other therapy is called refractory multiple myeloma. bortezomib.