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Multiple Myeloma
• Definition:
Multiple myeloma (MM), also sometimes called Kahler's disease, myelomatosis, or plasma cell myeloma, is cancer that originates in plasma cells. Multiple myeloma refers to a malignant tumor in hematological system, originating from plasma cells (a type of white blood cell generated in the bone marrow). Normal plasma cell is responsible for producing antibodies which can fight against infection, while malignant plasma cell---- myeloma cell proliferates in great numbers in the bone marrow.

Multiple Myeloma
Clinical manifestations are related to malignant behavior of plasma cells and abnormalities produced by M protein(monoclonal immunoglobulin)
• plasma cell proliferation:
multiple osteolytic bone lesions hypercalcemia bone marrow suppression ( pancytopenia )

• monoclonal M protein
decreased level of normal immunoglobulins hyperviscosity

Multiple Myeloma
Clinical symptoms: • • • • bone pains, pathologic fractures weakness and fatigue serious infection renal failure

calcium R .renal A – anemia B .bone .• • • • C .

thrombocytopenia • rouleaux in peripheral blood smears • marrow plasmacytosis > 10 -15% • hyperproteinemia • hypercalcemia • proteinuria • azotemia .Multiple Myeloma Laboratory tests: • ESR > 100 • anaemia.

Multiple Myeloma CAUSES • Is not known for sure • Decline in the immune system • Biological factors • Certain occupations • Exposure to certain chemicals • Exposure to radiation • Virus .

Blacks are about twice as likely to develop multiple myeloma as are whites. •Sex. Every year 1 percent of the people with MGUS in the United States develop multiple myeloma. •Obesity. •History of a monoclonal gammopathy of undetermined significance (MGUS). . with most diagnosed in their mid-60s. The majority of people who develop multiple myeloma are older than 50.Risk factors •Age. Men are more likely to develop the disease than are women. Few cases occur in people younger than 40. Your risk of multiple myeloma is increased if you're overweight or obese. •Race.

.Other factors that may increase your risk of developing multiple myeloma include exposure to radiation and working in petroleum-related industries.

Multiple myeloma is considered a hematological or blood cancer because it affects blood 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.Anatomy and physiology related to multiple myeloma Multiple myeloma is a cancer of the plasma cells. .

Plasmacytomas can also form outside of the bones and are called extramedullary plasmacytomas. the condition is called multiple myeloma. Normal bone marrow contains few plasma cells. . If there is only one tumour of myeloma cells in the bone. The myeloma cells can form tumours in bones called plasmacytomas. plasma cells are found in bone marrow. A person with multiple myeloma often has many abnormal plasma cells (myeloma cells) in the bone marrow. When many plasmacytomas are found in the bones. where blood cells are made. it is called a solitary plasmacytoma.Under normal circumstances.

minerals and vitamins. breastbone and skull. such as proteins.STRUCTURE Bone marrow is the soft. ribs. spongy substance in the centre of the bone where blood cells are made. Plasmacytomas usually develop in the areas where bone marrow is active. that are dissolved in the water. In adults. spine (vertebrae). Plasma is made up of water and chemicals. . Blood is made up of liquid (called plasma) and solid cells. the most active bone marrow is found in the pelvic and shoulder bones.

During the last stage of cell development. In both cell lines. which are still immature cells. the blasts mature into 3 types of blood cells. the stem cells become blasts. . stem cells begin to develop along either the lymphoid cell line or the myeloid cell line. The process of blood cell development is called hematopoiesis.All our blood cells develop from stem cells. In the earliest stage of cell development.


. • White blood cells help prevent and fight infection by destroying bacteria. viruses and other foreign cells or substances.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. • Platelets help the blood to clot when a blood vessel is damaged.

Different types of white blood cells work in different ways to protect the body from infection. . – B cells develop into plasma cells.White blood cells The immune system is the body's natural defence against infection. which produce antibodies to fight infection. – Natural killer (NK) cells attack any foreign cells. White blood cells are an important part of the immune system. including cancer cells.  lymphocytes – T cells recognize antigens and activate the B cells. They can also kill viruses and cancer cells.

• Eosinophils help control inflammation and allergic reactions.• Neutrophils and monocytes fight infection by ingesting or engulfing foreign cells. They attack and destroy certain parasitic organisms. such as bacteria. • Basophils play a role in certain allergic reactions. .

they turn into plasma cells. When B cells mature. .Multiple myeloma starts in B cells.

An antigen triggers plasma cells (B cells) to produce antibodies. antibodies and plasma cells Antigens are located on the surface of bacteria. Once plasma cells respond to an antigen. or immunoglobulins. . cancer cells and other foreign invaders. Antibodies are specific to a particular antigen. a plasma cell makes a new antibody. Antibodies. they will only make antibodies for that antigen. viruses. are special proteins that fight infection and defend the body against harmful foreign invaders. When the immune system identifies a new antigen. They circulate in the blood and attach to specific antigens on the surface of bacteria. viruses or other foreign substances.Antigens.

abnormal plasma cells make up 10%–30% of the cells in the bone marrow. The myeloma cells can collect in the bone marrow and crowd out the normal blood cells so they can’t work properly.In multiple myeloma. . Normally. In people with multiple myeloma. They begin to make many abnormal plasma cells (myeloma cells). plasma cells make up about 1% of the cells in bone marrow. B cells are damaged and do not work properly.

Each of the 5 types of immunoglobulins is named after the type of heavy chain that it contains. Immunoglobulins are made up of 4 parts called chains.Immunoglobulins Immunoglobulins (Ig) are protein molecules called antibodies produced by plasma cells. IgA. The 4 chains are attached to each other by special chemical bonds. IgD and IgE. IgM. There are 2 light chains and 2 heavy chains. There are 5 types of immunoglobulins – IgG. . 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.

 light chains •kappa •Lambda  heavy chains •IgG • IgA • IgM • IgD • IgE .


M-proteins can be measured in the blood and urine. Their presence indicates that there is a problem with the plasma cells. they make large amounts of one type of immunoglobulin (called a monoclonal immunoglobulin) and release it into the blood. The light chains that are not attached to heavy chains are called Bence Jones proteins. Sometimes the myeloma cells do not release immunoglobulin properly and only release the light chains into the blood. This monoclonal immunoglobulin is also called an M-protein.When damaged B cells develop into abnormal plasma cells (myeloma cells). .

This is because they release chemicals called cytokines that cause other cells to dissolve bone.Bone destruction Myeloma cells can damage the bone when they collect in the bone marrow. Cytokines also stimulate the growth of more myeloma cells and disrupt their normal life cycle. .

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. Thinning of the bone can also lead to osteoporosis. can be seen on an x-ray as dark circular spots in bones. lifting and coughing. These weakened areas of the bone may cause it to break under normal stresses like walking. . These areas of weakness. called osteolytic lesions.

Integrated PET-CT scan. X-ray. Bence Jones Protein Urine Test . Positron emission tomography (PET) scan. Computed tomography (CT or CAT) scan.DIAGNOSTIC TEST          Blood and urine tests. Fat pad aspirate. Magnetic resonance imaging (MRI). Bone marrow biopsy and aspiration.

these results are important for staging. Levels of the M protein in a patient's blood and urine are used to determine the extent of the disease and to monitor the effectiveness of treatment. calcium levels.Blood and urine tests. a small protein that plays a role in immunologic defense) are measured using blood tests. The levels of serum albumin (a blood protein made by the liver that is necessary for maintaining proper blood volume) and serum beta 2-microglobulin (β2-M. and blood counts (for possible anemia). Myeloma cells secrete an antibody known as the M protein (monoclonal immunoglobulin). Blood tests are also used to measure kidney function. .

An x-ray is a way to create a picture of the structures inside of your body using a small amount of radiation. .X-ray. X-rays are typically the first step in evaluating bones when myeloma is suspected or diagnosed.

which is located in the lower back by the hip. and other types of anesthesia (medication to block the awareness of pain) may be used. The skin in that area is usually numbed with medication beforehand.Bone marrow biopsy and aspiration. An aspiration removes a sample of fluid with a needle. Bone marrow has both a solid and a liquid part. and organs to diagnose disease. A common site for a bone marrow biopsy and aspiration is the pelvic bone. These two procedures are similar and often done at the same time. A bone marrow biopsy is the removal of a small amount of solid tissue using a needle. . The sample(s) are then analyzed by a pathologist. tissues. and it is important to making a diagnosis of myeloma. a doctor who specializes in interpreting laboratory tests and evaluating cells.

it can cause organ dysfunction. it may be necessary to take a sample of the abdominal fat pad (the collection of fat around a person's abdomen) for examination under a microscope. .Fat pad aspirate. If amyloidosis is a consideration. called a biopsy. This condition is called amyloidosis. If M proteins are deposited in body tissues.

proteins. . Results of these tests may help guide your treatment options. and other factors unique to the tumor.Molecular testing of the tumor. Your doctor may recommend running laboratory tests on a tumor sample to identify specific genes.

Magnetic resonance imaging (MRI). An MRI uses magnetic fields. especially in the skull. The detailed images may also show compression fractures of the spine or a tumor pressing on nerve roots. and pelvis. to produce detailed images of the body. . A contrast medium (a special dye) may be injected into a patient’s vein to create a clearer picture. An MRI can show replacement of normal bone marrow by myeloma cells or plasmacytoma (a plasma cell tumor growing in bone or soft tissue). spine. not x-rays.

cross-sectional view that shows any abnormalities or tumors in soft tissues.Computed tomography (CT or CAT) scan. A computer then combines these images into a three-dimensional picture of the inside of the body. a contrast medium is injected into a patient’s vein to provide better detail. . but it is used cautiously in patients with multiple myeloma because of a risk of kidney failure. Sometimes. A CT scan creates a detailed.

A PET scan is a way to create pictures of organs and tissues inside the body. A scanner then detects this substance to produce images of the inside of the body. A small amount of a radioactive substance is injected into a patient’s body. Because cancer tends to use energy actively. it absorbs more of the radioactive substance.Positron emission tomography (PET) scan. This substance is absorbed mainly by organs and tissues that produce the most energy. .

Integrated PET-CT scan. An integrated PET-CT scan combines the images from a positron emission tomography (PET) scan and a computed tomography (CT) scan. Together. . the two scans create a more complete image than either test can offer alone. performed at the same time on the same machine.

To do this test. You will collect it in a container that your doctor or the lab gives you.Bence-Jones Protein (Urine) The lab may measure the amount of Bence-Jones protein in a 24-hour urine sample. . you will need to collect all the urine you pass during a 24-hour period.

serum calcium.Staging of Multiple Myeloma Clinical staging • is based on level of haemoglobin. immunoglobulins and presence or not of lytic bone lesions • correlates with myeloma burden and prognosis I.creatinine < 2mg/dl B . High tumor mass • subclassification A .creatinine > 2mg/dl . Intermediate tumor mass III. Low tumor mass II.

STAGING • Stage 1 • Stage 2 • Stage 3 •A •B – Low amount of myeloma – Medium amount of myeloma – High amount of myeloma – Normal kidney function – Abnormal kidney function .

Doxorubicin (Adriamycin) and liposomal doxorubicin (Doxil)  Newer drugs such as thalidomide (Thalomid). and better supportive care.TREATMENT The treatment of multiple myeloma (MM) is complex because of rapid advances in stem cell transplantation. medications. which have led to improved survival for patients with multiple myeloma over the past thirty years. and pomalidomide (Pomalyst)  Corticosteroids such as prednisone or dexamethasone (Decadron)  Stem cell (bone marrow) transplantation . carfilzomib (Kyprolis). cyclophosphamide (Cytoxan). The main options for therapy include:  Standard chemotherapy drugs such as melphalan (Alkeran). bortezomib (Velcade). lenalidomide (Revlimid).

chemotherapy leads to complete remission. or with standard chemotherapy agents. these agents are used in combination with dexamethasone. rarely.Types of treatment — There are four main types of treatment:  Chemotherapy — In most people. both in newly diagnosed patients and in patients with advanced disease who have failed chemotherapy or transplantation.  Newer Drugs — Drugs such as thalidomide (Thalomid). carfilzomib (Kyprolis). . lenalidomide (Revlimid). bortezomib (Velcade). with each other. and pomalidomide (Pomalyst) have emerged as important options for treatment of myeloma. chemotherapy partially controls multiple myeloma. In most cases.  Corticosteroids — Corticosteroids include dexamethasone (Decadron) or prednisone.

Autologous transplants for multiple myeloma are very safe in centers with experience in the procedure. Sometimes. In multiple myeloma. Such transplants. 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). have been shown to prolong life in selected patients. most transplants performed are of the autologous kind. . although not curative. They can be done as initial therapy in newly diagnosed patients or at the time of relapse. in selected patients more than one transplant may be recommended to adequately control the disease.

MPT Melphalan prednisone thalidomide (MPT) chemotherapy — The combination of melphalan. 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. prednisone. .

Thalidomide is absolutely UNSAFE (contraindicated) for pregnant women. 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. .

bortezomib/dexamethasone. In such situations. dexamethasone (VTD) is preferred.Melphalan is not usually recommended for people who have kidney failure. thalidomide. thalidomide/dexamethasone. . or bortezomib.

although few people with multiple myeloma have an identical twin who can serve as a donor. based on the source of the stem cells: • Autologous transplantation: the stem cells are obtained from the individual with multiple myeloma. • Syngeneic transplantation: the stem cells or bone marrow are obtained from an identical twin of the individual. • Allogeneic transplantation: the stem cells or bone marrow are obtained from a donor with a tissue type matching that of the patient. This is the type of transplantation that is most commonly recommended.STEM CELL TRANSPLANTATION Stem cell transplantation is a treatment option for some individuals with multiple myeloma. This type of transplantation carries very high risks and is not recommended for most individuals with multiple myeloma. . There are three types of transplantation. This is the optimal form of transplantation.