Anatomy and Physiology Related to Multiple Myelom1

7/27/2019 Anatomy and Physiology Related to Multiple Myelom1

1/15

Anatomy and physiology related to multiple myeloma

Multiple myeloma is a cancer of the plasma cells. Plasma cells are found in the bone marrowand other tissues and

organs. They are a type of white blood cell that makeantibodies. 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.
http://www.cancer.ca/glossary?CCEID=9844&culture=enhttp://www.cancer.ca/glossary?CCEID=9844&culture=enhttp://www.cancer.ca/glossary?CCEID=9844&culture=enhttp://www.cancer.ca/glossary?CCEID=9115&culture=enhttp://www.cancer.ca/glossary?CCEID=9115&culture=enhttp://www.cancer.ca/glossary?CCEID=9115&culture=enhttp://www.cancer.ca/glossary?CCEID=9115&culture=enhttp://www.cancer.ca/glossary?CCEID=9844&culture=en


2/15

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.

White blood cells help prevent and fight infection by destroying bacteria, viruses and

other foreign cells or substances.

White blood cellsTheimmune systemis the body's natural defence against infection. White blood cells are an important part of the

immune system. Different types of white blood cells work in different ways to protect the body from infection.

lymphocytes

o T cells recognize antigens and activate the B cells. They can also kill viruses and cancer

cells.
http://www.cancer.ca/en/cancer-information/cancer-101/what-is-cancer/the-immune-system/?region=qchttp://www.cancer.ca/en/cancer-information/cancer-101/what-is-cancer/the-immune-system/?region=qchttp://www.cancer.ca/en/cancer-information/cancer-101/what-is-cancer/the-immune-system/?region=qchttp://www.cancer.ca/glossary?CCEID=9242&culture=enhttp://www.cancer.ca/glossary?CCEID=9242&culture=enhttp://www.cancer.ca/glossary?CCEID=9242&culture=enhttp://www.cancer.ca/en/cancer-information/cancer-101/what-is-cancer/the-immune-system/?region=qc


3/15

o B cells develop into plasma cells, which produce antibodies to fight infection.

o Natural killer (NK) cells attack any foreign cells, including cancer cells.

Neutrophils and monocytes fight infection by ingesting or engulfing foreign cells, such

as bacteria.

Eosinophils help control inflammation and allergic reactions. They attack and destroy

certain parasitic organisms.

Basophils play a role in certain allergic reactions.

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

Antigens, antibodies and plasma cells

Antigens are located on the surface of bacteria, viruses, cancer cells and other foreign invaders. An antigen triggers plasma

cells (B cells) to produce antibodies.

Antibodies, or immunoglobulins, are special proteins that fight infection and defend the body against harmful foreign

invaders. They circulate in the blood and attach to specific antigens on the surface of bacteria, viruses or other foreign

substances.

Antibodies are specific to a particular antigen. When the immune system identifies a new antigen, a plasma cell makes a new

antibody. Once plasma cells respond to an antigen, they will only make antibodies for that antigen.

In multiple myeloma, B cells are damaged and do not work properly. They begin to make many abnormal plasma cells

(myeloma cells). The myeloma cells can collect in the bone marrow and crowd out the normal blood cells so they cant work

properly. Normally, plasma cells make up about 1% of the cells in bone marrow. In people with multiple myeloma, abnormal

plasma cells make up 10%30% of the cells in the bone marrow.

Immunoglobulins

Immunoglobulins (Ig) are protein molecules called antibodies produced by plasma cells. There are 5 types of

immunoglobulins IgG, IgA, IgM, IgD and IgE. Immunoglobulins are made up of 4 parts called chains. There are 2 light


4/15

chains and 2 heavy chains. Each of the 5 types of immunoglobulins is named after the type of heavy chain that it contains.

The 4 chains are attached to each other by special chemical bonds. 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

o kappa

o lambda

heavy chains

o IgG

o IgA

o IgM

o IgD

o IgE

When damaged B cells develop into abnormal plasma cells (myeloma cells), they make large amounts of one type of

immunoglobulin (called a monoclonal immunoglobulin) and release it into the blood. This monoclonal immunoglobulin is alsocalled an M-protein. M-proteins can be measured in the blood and urine. Their presence indicates that there is a problem

with the plasma cells.

Sometimes the myeloma cells do not release immunoglobulin properly and only release the light chains into the blood. The

light chains that are not attached to heavy chains are called Bence Jones proteins.

Bone destruction


5/15


6/15

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 containhemoglobin, which is the molecule that carries oxygen to the tissues. A decrease

in thenumber of red blood cellsreduces the amount of oxygen that can be carried by the bloodstream.

This can result in poorexercisetolerance andfatigue.

Normal ranges for the totalnumber of red blood cellsin adults are:

4.6-6.2 million per cubic millimeter (males)

4.2-5.4 million per cubic millimeter (females)

White Blood Cells

White blood cells are an important part of the immune system. There are several types of white cells

(leukocytes) present in the blood. These cells mainly function to fight infection. Normal total ranges for

white blood cells are: 4,500 - 11,000 (per cubic millimeter). Slightly higher counts are normal in

children.

A white blood cell differential reports the percentages of the dif ferent types of white blood cells that

comprise the totalwhite blood cell count. These values are reported as a percentage of the total number

of cells.

Cell Type % Of Total WBC's

Neutrophils 47% to 77% (elevated in infection,inflammation, andstress)

Bands 0% to 3% (elevated in some cases of bacterialinfection)

Lymphocytes 16% to 43% (elevated in some cases of viralinfection and someleukemias)

Monocytes 0.5% to 10% (elevated in some viral, fungal&TBinfections,lupus,cancer)

Basophils 0.3% to 2% (elevated in someleukemias,somecancers, andhypothyroidism)

Eosinophils 0.3% to 7% (elevated in
http://www.freemd.com/multiple-myeloma/anatomy.htm#/et/hemoglobin.htmhttp://www.freemd.com/multiple-myeloma/anatomy.htm#/et/hemoglobin.htmhttp://www.freemd.com/multiple-myeloma/anatomy.htm#/et/hemoglobin.htmhttp://www.freemd.com/multiple-myeloma/anatomy.htm#/et/number-of-red-blood-cells.htmhttp://www.freemd.com/multiple-myeloma/anatomy.htm#/et/number-of-red-blood-cells.htmhttp://www.freemd.com/multiple-myeloma/anatomy.htm#/et/number-of-red-blood-cells.htmhttp://www.freemd.com/mens-health/prevention-exercise.htmhttp://www.freemd.com/mens-health/prevention-exercise.htmhttp://www.freemd.com/mens-health/prevention-exercise.htmhttp://www.freemd.com/weakness-or-fatigue/overview.htmhttp://www.freemd.com/weakness-or-fatigue/overview.htmhttp://www.freemd.com/weakness-or-fatigue/overview.htmhttp://www.freemd.com/multiple-myeloma/anatomy.htm#/et/number-of-red-blood-cells.htmhttp://www.freemd.com/multiple-myeloma/anatomy.htm#/et/number-of-red-blood-cells.htmhttp://www.freemd.com/multiple-myeloma/anatomy.htm#/et/number-of-red-blood-cells.htmhttp://www.freemd.com/multiple-myeloma/anatomy.htm#/et/white-blood-cell-count.htmhttp://www.freemd.com/multiple-myeloma/anatomy.htm#/et/white-blood-cell-count.htmhttp://www.freemd.com/multiple-myeloma/anatomy.htm#/et/white-blood-cell-count.htmhttp://www.freemd.com/stress-reaction/overview.htmhttp://www.freemd.com/stress-reaction/overview.htmhttp://www.freemd.com/leukemia/overview.htmhttp://www.freemd.com/leukemia/overview.htmhttp://www.freemd.com/leukemia/overview.htmhttp://www.freemd.com/tuberculosis/overview.htmhttp://www.freemd.com/tuberculosis/overview.htmhttp://www.freemd.com/tuberculosis/overview.htmhttp://www.freemd.com/lupus/overview.htmhttp://www.freemd.com/lupus/overview.htmhttp://www.freemd.com/lupus/overview.htmhttp://www.freemd.com/cancer/overview.htmhttp://www.freemd.com/cancer/overview.htmhttp://www.freemd.com/cancer/overview.htmhttp://www.freemd.com/leukemia/overview.htmhttp://www.freemd.com/leukemia/overview.htmhttp://www.freemd.com/leukemia/overview.htmhttp://www.freemd.com/cancer/overview.htmhttp://www.freemd.com/cancer/overview.htmhttp://www.freemd.com/cancer/overview.htmhttp://www.freemd.com/hypothyroidism/overview.htmhttp://www.freemd.com/hypothyroidism/overview.htmhttp://www.freemd.com/hypothyroidism/overview.htmhttp://www.freemd.com/multiple-myeloma/anatomy.htmhttp://www.freemd.com/multiple-myeloma/anatomy.htmhttp://www.freemd.com/multiple-myeloma/anatomy.htmhttp://www.freemd.com/multiple-myeloma/anatomy.htmhttp://www.freemd.com/multiple-myeloma/anatomy.htmhttp://www.freemd.com/multiple-myeloma/anatomy.htmhttp://www.freemd.com/multiple-myeloma/anatomy.htmhttp://www.freemd.com/multiple-myeloma/anatomy.htmhttp://www.freemd.com/multiple-myeloma/anatomy.htmhttp://www.freemd.com/multiple-myeloma/anatomy.htmhttp://www.freemd.com/multiple-myeloma/anatomy.htmhttp://www.freemd.com/multiple-myeloma/anatomy.htmhttp://www.freemd.com/multiple-myeloma/anatomy.htmhttp://www.freemd.com/multiple-myeloma/anatomy.htmhttp://www.freemd.com/multiple-myeloma/anatomy.htmhttp://www.freemd.com/multiple-myeloma/anatomy.htmhttp://www.freemd.com/multiple-myeloma/anatomy.htmhttp://www.freemd.com/multiple-myeloma/anatomy.htmhttp://www.freemd.com/multiple-myeloma/anatomy.htmhttp://www.freemd.com/multiple-myeloma/anatomy.htmhttp://www.freemd.com/multiple-myeloma/anatomy.htmhttp://www.freemd.com/multiple-myeloma/anatomy.htmhttp://www.freemd.com/multiple-myeloma/anatomy.htmhttp://www.freemd.com/multiple-myeloma/anatomy.htmhttp://www.freemd.com/multiple-myeloma/anatomy.htmhttp://www.freemd.com/multiple-myeloma/anatomy.htmhttp://www.freemd.com/multiple-myeloma/anatomy.htmhttp://www.freemd.com/multiple-myeloma/anatomy.htmhttp://www.freemd.com/multiple-myeloma/anatomy.htmhttp://www.freemd.com/multiple-myeloma/anatomy.htmhttp://www.freemd.com/multiple-myeloma/anatomy.htmhttp://www.freemd.com/multiple-myeloma/anatomy.htmhttp://www.freemd.com/multiple-myeloma/anatomy.htmhttp://www.freemd.com/multiple-myeloma/anatomy.htmhttp://www.freemd.com/multiple-myeloma/anatomy.htmhttp://www.freemd.com/multiple-myeloma/anatomy.htmhttp://www.freemd.com/hypothyroidism/overview.htmhttp://www.freemd.com/cancer/overview.htmhttp://www.freemd.com/leukemia/overview.htmhttp://www.freemd.com/cancer/overview.htmhttp://www.freemd.com/lupus/overview.htmhttp://www.freemd.com/tuberculosis/overview.htmhttp://www.freemd.com/leukemia/overview.htmhttp://www.freemd.com/stress-reaction/overview.htmhttp://www.freemd.com/multiple-myeloma/anatomy.htm#/et/white-blood-cell-count.htmhttp://www.freemd.com/multiple-myeloma/anatomy.htm#/et/number-of-red-blood-cells.htmhttp://www.freemd.com/weakness-or-fatigue/overview.htmhttp://www.freemd.com/mens-health/prevention-exercise.htmhttp://www.freemd.com/multiple-myeloma/anatomy.htm#/et/number-of-red-blood-cells.htmhttp://www.freemd.com/multiple-myeloma/anatomy.htm#/et/hemoglobin.htm


7/15


8/15

although not curative, have been shown to prolong life in selected patients. They can be done as

initial therapy in newly diagnosed patients or at the time of relapse. Sometimes, in selected

patients more than one transplant may be recommended to adequately control the disease.

Autologous transplants for multiple myeloma are very safe in centers with experience in the

procedure.

When to start treatment? Multiple myeloma can remain stable for prolonged periods of time.

Individuals with early myeloma who have no symptoms (often called smoldering myeloma) may be

advised to wait months to years before considering chemotherapy.

Individuals with a related condition, called monoclonal gammopathy of undetermined significance

(MGUS), do not require treatment, although long-term follow-up is needed; a small percentage of patients

with MGUS will eventually develop full-blown myeloma.

However, once symptoms develop, treatment with one or more of the options discussed above is

recommended for almost all patients.

Is stem cell transplantation an option? Because of the risk of toxic and even fatal complications

related to stem cell transplantation, not everyone with multiple myeloma is a candidate for stem celltransplantation. Eligibility varies across countries and across institutions. In most European countries,

stem cell transplantation for multiple myeloma is offered primarily to patients less than 65 years of age. In

the United States, a strict age-limit is not used. Instead, decisions are made on a case-by-case basis

based upon a person's health and vary across institutions.

In most centers in the United States, patients with multiple myeloma who have one or more of the

following factors are NOT considered eligible for transplantation:

Age >77 years

Direct bilirubin >2.0 mg/dL (an elevated bilirubin level indicates that the liver may not tolerate the

high dose chemotherapy required before transplantation)

Serum creatinine >2.5 mg/dL (221 mol/liter) unless on chronic stable dialysis (creatinine is a

reflection of kidney function; 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, these factors are guidelines; the decision regarding transplant eligibility should be made by the

patient and physician after discussing the potential risks, benefits, and the needs and wishes of the

patient.

TREATMENT OF NEWLY DIAGNOSED MULTIPLE MYELOMA

The initial choice of chemotherapy depends upon the patient's health, age, ability to undergo stem cell

transplantation in the future and disease characteristics that denote high, intermediate, or standard risk

multiple myeloma [2]. High versus standard risk multiple myeloma is discussed separately. (See"Patient

information: Multiple myeloma symptoms, diagnosis, and staging (Beyond the Basics)", section on 'Risk

stratification'.)
http://www.uptodate.com/contents/image?imageKey=HEME%2F72901&topicKey=PI%2F690&source=see_linkhttp://www.uptodate.com/contents/image?imageKey=HEME%2F72901&topicKey=PI%2F690&source=see_linkhttp://www.uptodate.com/contents/image?imageKey=HEME%2F72901&topicKey=PI%2F690&source=see_linkhttp://www.uptodate.com/contents/image?imageKey=CARD%2F52683&topicKey=PI%2F690&source=see_linkhttp://www.uptodate.com/contents/image?imageKey=CARD%2F52683&topicKey=PI%2F690&source=see_linkhttp://www.uptodate.com/contents/image?imageKey=CARD%2F52683&topicKey=PI%2F690&source=see_linkhttp://www.uptodate.com/contents/multiple-myeloma-treatment-beyond-the-basics/abstract/2http://www.uptodate.com/contents/multiple-myeloma-treatment-beyond-the-basics/abstract/2http://www.uptodate.com/contents/multiple-myeloma-treatment-beyond-the-basics/abstract/2http://www.uptodate.com/contents/multiple-myeloma-symptoms-diagnosis-and-staging-beyond-the-basics?source=see_link&anchor=H18#H18http://www.uptodate.com/contents/multiple-myeloma-symptoms-diagnosis-and-staging-beyond-the-basics?source=see_link&anchor=H18#H18http://www.uptodate.com/contents/multiple-myeloma-symptoms-diagnosis-and-staging-beyond-the-basics?source=see_link&anchor=H18#H18http://www.uptodate.com/contents/multiple-myeloma-symptoms-diagnosis-and-staging-beyond-the-basics?source=see_link&anchor=H18#H18http://www.uptodate.com/contents/multiple-myeloma-symptoms-diagnosis-and-staging-beyond-the-basics?source=see_link&anchor=H18#H18http://www.uptodate.com/contents/multiple-myeloma-symptoms-diagnosis-and-staging-beyond-the-basics?source=see_link&anchor=H18#H18http://www.uptodate.com/contents/multiple-myeloma-symptoms-diagnosis-and-staging-beyond-the-basics?source=see_link&anchor=H18#H18http://www.uptodate.com/contents/multiple-myeloma-symptoms-diagnosis-and-staging-beyond-the-basics?source=see_link&anchor=H18#H18http://www.uptodate.com/contents/multiple-myeloma-treatment-beyond-the-basics/abstract/2http://www.uptodate.com/contents/image?imageKey=CARD%2F52683&topicKey=PI%2F690&source=see_linkhttp://www.uptodate.com/contents/image?imageKey=HEME%2F72901&topicKey=PI%2F690&source=see_link


9/15


10/15

Melphalan and prednisone are taken by mouth, usually on days one through four every six weeks. Each 6

week interval is called a cycle; a total of 12 cycles is usually recommended. Thalidomide is taken every

day until the 12 cycles are completed. It may take 6 to 12 months or even longer for blood tests to reflect

the full effects of this chemotherapy on multiple myeloma. The average survival among individuals treated

with MPT is four years.

During MPT chemotherapy, 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). The dose of

melphalan must be adjusted based on these findings.

Lenalidomide Lenalidomide (Revlimid) is an immune-modulating drug that is effective in the initial

treatment of multiple myeloma, usually in combination with dexamethasone. This combination is one of

the preferred initial treatment for people with multiple myeloma who are planning to have stem cell

transplantation. Both medications are taken as a pill; lenalidomide is taken for 21 of 28 days, along with

dexamethasone, which is taken once per week.

The combination of lenalidomide with dexamethasone increases the chance of developing blood clots; an

anticoagulant (eg, aspirin or warfarin) is usually recommended to reduce this risk. Lenalidomide has the

potential to cause severe birth defects; it is absolutely unsafe(contraindicated) for pregnant women.

Thalidomide (Thalomid) plus dexamethasone is an alternative to lenalidomide plus dexamethasone,

although it may not be as effective and may have more toxic side effects. The risks of thalidomide are

similar to those of lenalidomide.

Bortezomib Bortezomib (Velcade) is a medication that is effective in treating patients with multiple

myeloma and other tumors. It is also especially useful in people with kidney failure and those with high-

risk multiple myeloma. Bortezomib is given intravenously or subcutaneously, and its main side effects are

low blood counts and nerve damage.

Treatment-related infections There is an increased risk of infection during the first two months of

chemotherapy or immune modulating therapy. As many as one-third of these infections are fatal and, in

many cases, they limit the ability to administer chemotherapy. In some centers, daily antibiotics are given

during the first two months of chemotherapy to reduce the risk or severity of infections. However, other

centers do not routinely recommend preventive antibiotics.

In all cases, vaccination against influenza and pneumonia is strongly recommended before starting

chemotherapy. (See"Patient information: Adult vaccines (Beyond the Basics)".)

Plateau phase Chemotherapy is usually continued until multiple myeloma enters a stable (plateau)

phase. The plateau phase is reached when the myeloma becomes stable and shows no signs of

progressing. Although this phase is usually temporary, it typically lasts six months or longer. The plateau

phase occurs in about one half of individuals after chemotherapy.

Achieving this phase usually requires at least s ix cycles of treatment, although some people requireadditional cycles to reach the plateau phase. People with standard risk multiple myeloma do not usually

require additional chemotherapy during the plateau phase. However, some physicians recommend

maintenance chemotherapy for people with high risk multiple myeloma (see'High risk multiple myeloma

treatment options'above).

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.
http://www.uptodate.com/contents/adult-vaccines-beyond-the-basics?source=see_linkhttp://www.uptodate.com/contents/adult-vaccines-beyond-the-basics?source=see_linkhttp://www.uptodate.com/contents/adult-vaccines-beyond-the-basics?source=see_linkhttp://www.uptodate.com/contents/multiple-myeloma-treatment-beyond-the-basics#H7http://www.uptodate.com/contents/multiple-myeloma-treatment-beyond-the-basics#H7http://www.uptodate.com/contents/multiple-myeloma-treatment-beyond-the-basics#H7http://www.uptodate.com/contents/multiple-myeloma-treatment-beyond-the-basics#H7http://www.uptodate.com/contents/multiple-myeloma-treatment-beyond-the-basics#H7http://www.uptodate.com/contents/multiple-myeloma-treatment-beyond-the-basics#H7http://www.uptodate.com/contents/adult-vaccines-beyond-the-basics?source=see_link


11/15

STEM CELL TRANSPLANTATION

Stem cell transplantation is a treatment option for some individuals with multiple myeloma. There are

three types of transplantation, based on the source of the stem cells:

Autologous transplantation: the stem cells are obtained from the individual with multiple myeloma.This is the type of transplantation that is most commonly recommended.

Allogeneic transplantation: the stem cells or bone marrow are obtained from a donor with a tissue

type matching that of the patient. This type of transplantation carries very high risks and is not

recommended for most individuals with multiple myeloma.

Syngeneic transplantation: the stem cells or bone marrow are obtained from an identical twin of

the individual. This is the optimal form of transplantation, although few people with multiple

myeloma have an identical twin who can serve as a donor.

Transplantation, when successful, prolongs survival, leads to a remission, and, infrequently, cures

multiple myeloma. However, transplantation has several limitations. The high-dose chemotherapy given

before transplantation usually fails to kill all of the plasma cells, allowing the condition to relapse after

transplantation. Such treatment also puts the patient at risk for serious infections and bleeding, which can

be fatal. (See"Patient information: Bone marrow transplantation (stem cell transplantation) (Beyond the

Basics)".)

Autologous stem cell transplantation Autologous stem cell transplantation refers to transplantation

with a person's own stem cells. During this procedure, stem cells are collected and frozen for later use.

High-dose chemotherapy is then given to kill as many plasma cells as possible, and the stem cells are

thawed and returned to the patient. 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.

At present, autologous stem cell transplantation is appropriate for up to 50 percent of people with multiple

myeloma. Autologous stem cell transplantation is not recommended for individuals with smoldering

myeloma.

Procedure After initial therapy with a regimen such as lenalidomide/dexamethasone or bortezomib,

cyclophosphamide, dexamethasone (VCD) for three to four months, 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. If there are not sufficient numbers of stem cells in the blood after

G-CSF or GM-CSF, another agent, called Plerixafor, may be added to help with collection. Stem cells are

then collected from the blood, frozen, and stored for later use.

After an individual recovers from the stem cell collection, he or she is given high-dose chemotherapy with

melphalan (or similar drugs) to kill as many of the malignant plasma cells as possible; then the previously

collected stem cells are thawed and returned to the patient. In about one-half of patients, this procedurecan be done on an outpatient basis.

Alternatively, after stem cell collection, an individual may be given standard chemotherapy to achieve a

plateau phase. At the time of relapse, high doses of melphalan (or similar drugs) are given, and the

previously collected stem cells are returned to the patient; this is called delayed transplantation.

Single versus double autologous transplantation Double autologous transplantation (two

consecutive autologous transplantations) may be more effective than single autologous transplantation if
http://www.uptodate.com/contents/bone-marrow-transplantation-stem-cell-transplantation-beyond-the-basics?source=see_linkhttp://www.uptodate.com/contents/bone-marrow-transplantation-stem-cell-transplantation-beyond-the-basics?source=see_linkhttp://www.uptodate.com/contents/bone-marrow-transplantation-stem-cell-transplantation-beyond-the-basics?source=see_linkhttp://www.uptodate.com/contents/bone-marrow-transplantation-stem-cell-transplantation-beyond-the-basics?source=see_linkhttp://www.uptodate.com/contents/bone-marrow-transplantation-stem-cell-transplantation-beyond-the-basics?source=see_linkhttp://www.uptodate.com/contents/bone-marrow-transplantation-stem-cell-transplantation-beyond-the-basics?source=see_link


12/15

the first transplant has not produced a complete or near complete response. The second transplantation

is usually performed within six months of the first.

Among individuals undergoing double transplantation, 51 percent have a complete response, lasting, on

average, 50 months. 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.

Role of age and stage of myeloma Because autologous stem cell transplantation has serious side

effects, it is generally not recommended for individuals over the age of 70. However, this procedure may

be an option for some people over age 70 who are otherwise healthy. 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.

Importance of prior treatment Autologous transplantation is not recommended for people who have

received prolonged chemotherapy with alkylating drugs (such as melphalan). This is because it is often

difficult to collect a sufficient number of healthy stem cells for transplantation. Other treatments commonly

used for multiple myeloma, including thalidomide, bortezomib, and lenalidomide, are safe to take before

stem cell transplantation.

Effectiveness About 1 percent of individuals die from complications related to autologous

transplantation. However, compared with chemotherapy alone, autologous stem cell transplantation is

more likely to produce a response, and is associated with 12-month longer survival compared to

chemotherapy alone (approximately 57 versus 44 months) [3].

Allogeneic bone marrow transplantation Allogeneic transplantation requires bone marrow or stem

cells from a donor with a matching tissue type. Unfortunately, approximately 25 percent of individuals who

undergo allogeneic transplantation die from transplant-related complications, such as infection, lung

inflammation, and graft-versus-host disease. Primarily because of this toxicity and the lack of clear

benefit, allogeneic transplantation is seldom used for the treatment of myeloma.

Syngeneic transplantation

A syngeneic transplantation refers to a transplantation between identical

twins. For individuals who have an identical twin, this treatment option is more effective than either

autologous or allogeneic transplantation.

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.

This type of remission occurs in about 4 percent of individuals after autologous transplantation.

TREATMENT OF MULTIPLE MYELOMA COMPLICATIONS

Multiple myeloma can cause a variety of complications, some of which are life-threatening.

High blood calcium levels

High blood calcium levels develop as bone is lost. Individuals with MMshould remain as active as possible because physical activity helps counter bone loss.

The treatment of high blood calcium levels usually includes the use of intravenous fluids and prednisone.

If this treatment is not effective, treatment with drugs that act against bone loss, such as zoledronic acid

(Zometa) or pamidronate (Aredia), a class of drugs called bisphosphonates, may be recommended.

Impaired kidney function Kidney function becomes impaired in about one half of individuals with

multiple myeloma. The treatment of impaired kidney function is aimed at the specific underlying cause.
http://www.uptodate.com/contents/multiple-myeloma-treatment-beyond-the-basics/abstract/3http://www.uptodate.com/contents/multiple-myeloma-treatment-beyond-the-basics/abstract/3http://www.uptodate.com/contents/multiple-myeloma-treatment-beyond-the-basics/abstract/3http://www.uptodate.com/contents/multiple-myeloma-treatment-beyond-the-basics/abstract/3


13/15

Treatment usually includes intravenous fluids; it may also include dialysis (a type of blood filtration used

for kidney failure), prednisone (a steroid that can indirectly lower blood calcium levels), and allopurinol, a

drug that can lower blood levels of uric acid, a waste product from the increased turnover of the malignant

plasma cells, which can damage the kidneys.

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). They should also avoid

using any nonsteroidal anti-inflammatory drugs (NSAIDs, such as Advil, Motrin, Aleve) because these

drugs might worsen kidney function.

If impaired kidney function has progressed to kidney failure, the treatment options include hemodialysis or

peritoneal dialysis. Advanced degrees of kidney failure are usually not reversible even if the multiple

myeloma later responds to treatment. (See"Patient information: Dialysis or kidney transplantation

which is right for me? (Beyond the Basics)".)

Infection Bacterial infections, often indicated by the presence of fever, require prompt treatment with

antibiotics. Daily use of the antibiotic trimethoprim-sulfamethoxazole (Bactrim) can help prevent

infections. Individuals who get frequent infections may be advised to take penicillin daily or rarely to have

periodic intravenous infusions of gamma globulin.

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). (See"Patient

information: Influenza symptoms and treatment (Beyond the Basics)".)

Bone pain and fractures Physical activity, with careful avoidance of injury, can promote bone strength

in individuals with multiple myeloma. The bone pain associated with multiple myeloma can be controlled

with chemotherapy, analgesics (pain relieving drugs), radiation, 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.

In individuals who have early signs of bone erosion, bisphosphonates reduce the risk of fractures and

reduce bone pain. Therefore, bisphosphonates are recommended for all individuals who have early signs

of bone erosions on x-rays. Bisphosphonates are usually given by intravenous infusion every four weeks;

this treatment is continued for approximately two years. These medications may affect kidney function,

which should be monitored on a regular basis to avoid this complication.

Dental procedures, such as root canal or extraction of teeth, may be associated with infection or

destruction of the jaw (osteonecrosis) in patients treated with intravenous bisphosphonates. Accordingly,

patients should avoid such procedures, if possible, while taking these agents; any needed dental

procedures should be performed before these agents are started.

Spinal cord compression Spinal cord compression is a medical emergency that requires prompt

treatment to prevent irreversible damage, such as paralysis. Initial treatment may consist of radiation and

dexamethasone (a steroid) to reduce swelling around the spinal cord; if these measures are not effective,surgery is needed to relieve pressure on the spinal cord. Patients should call their doctor immediately if

they have severe back pain; weakness, numbness, or tingling in the legs; or new problems with control

over their bladder or bowel (incontinence).

Anemia Anemia (low red blood cell count) that is causing symptoms may require blood transfusions or

treatment with erythropoietin (EPO), a substance that stimulates the production of red blood cells.

Erythropoietin is usually given by injection one to three times per week. This treatment effectively
http://www.uptodate.com/contents/dialysis-or-kidney-transplantation-which-is-right-for-me-beyond-the-basics?source=see_linkhttp://www.uptodate.com/contents/dialysis-or-kidney-transplantation-which-is-right-for-me-beyond-the-basics?source=see_linkhttp://www.uptodate.com/contents/dialysis-or-kidney-transplantation-which-is-right-for-me-beyond-the-basics?source=see_linkhttp://www.uptodate.com/contents/dialysis-or-kidney-transplantation-which-is-right-for-me-beyond-the-basics?source=see_linkhttp://www.uptodate.com/contents/dialysis-or-kidney-transplantation-which-is-right-for-me-beyond-the-basics?source=see_linkhttp://www.uptodate.com/contents/dialysis-or-kidney-transplantation-which-is-right-for-me-beyond-the-basics?source=see_linkhttp://www.uptodate.com/contents/influenza-symptoms-and-treatment-beyond-the-basics?source=see_linkhttp://www.uptodate.com/contents/influenza-symptoms-and-treatment-beyond-the-basics?source=see_linkhttp://www.uptodate.com/contents/influenza-symptoms-and-treatment-beyond-the-basics?source=see_linkhttp://www.uptodate.com/contents/influenza-symptoms-and-treatment-beyond-the-basics?source=see_linkhttp://www.uptodate.com/contents/influenza-symptoms-and-treatment-beyond-the-basics?source=see_linkhttp://www.uptodate.com/contents/influenza-symptoms-and-treatment-beyond-the-basics?source=see_linkhttp://www.uptodate.com/contents/dialysis-or-kidney-transplantation-which-is-right-for-me-beyond-the-basics?source=see_linkhttp://www.uptodate.com/contents/dialysis-or-kidney-transplantation-which-is-right-for-me-beyond-the-basics?source=see_link


14/15

increases levels of hemoglobin (the protein in red blood cells that helps carry oxygen to the tissues),

improves symptoms, and reduces the need for blood transfusion.

Thickening of the blood Thickening of the blood (called hyperviscosity syndrome) rarely occurs in

individuals with multiple myeloma. This complication is treated with plasmapheresis, a type of blood

filtration that removes the excess monoclonal proteins responsible for the increased viscosity.

TREATMENT OF RELAPSED OR REFRACTORY MULTIPLE MYELOMA

Almost all patients with multiple myeloma eventually relapse, and a modest percentage are resistant to

initial treatment.

Multiple myeloma that responds poorly or not at all to melphalan-prednisone thalidomide or other therapy

is called refractory multiple myeloma. This condition can occur during initial chemotherapy or during

chemotherapy given after a relapse. Refractory multiple myeloma is more difficult to treat.

Thalidomide, bortezomib, lenalidomide, carfilzomib, or pomalidomide, given with steroids, and/or standard

chemotherapy drugs such as melphalan or cyclophosphamide, form the major treatment options for

relapsed or resistant disease.

Relapses occurring more than six months after completing chemotherapy are often treated by

resuming the initial chemotherapy. Most individuals will again have a response to chemotherapy

when it is given a second time, although the response is usually shorter and smaller than the

original response. Selected patients can consider autologous stem cell transplantation.

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. Said another way, if a person

does not respond to induction chemotherapy, he or she may still respond to autologous stem cell

transplantation.


15/15

Anatomy and Physiology Related to Multiple Myelom1

Documents

Transcript of Anatomy and Physiology Related to Multiple Myelom1