Hope and Watchful Waiting

People who choose watchful waiting put off having cancer treatment until they have symptoms. Doctors sometimes suggest watchful waiting for people with indolent lymphoma. People with indolent lymphoma may not have problems that require cancer treatment for a long time. Sometimes the tumor may even shrink for a while without therapy. By putting off treatment, they can avoid the side effects of chemotherapy or radiation therapy.
If you and your doctor agree that watchful waiting is a good idea, the doctor will check you regularly (every 3 months). You will receive treatment if symptoms occur or get worse.
Some people do not choose watchful waiting because they don't want to worry about having cancer that is not treated. Those who choose watchful waiting but later become worried should discuss their feelings with the doctor.

Questions to ask before starting Treatment

• What type of lymphoma do I have? May I have a copy of the report from the pathologist?
• What is the stage of my disease? Where are the tumors?
• What are my treatment choices? Which do you recommend for me? Why?
• Will I have more than one kind of treatment?
• What are the expected benefits of each kind of treatment? How will we know the treatment is working? What tests will be used to check its effectiveness? How often will I get these tests?
• What are the risks and possible side effects of each treatment? What can we do to control the side effects?
• How long will treatment last?
• Will I have to stay in the hospital? If so, for how long?
• What can I do to take care of myself during treatment?
• What is the treatment likely to cost? Will my insurance cover the cost?
• How will treatment affect my normal activities?
• Would a clinical trial be right for me?
• How often will I need checkups?

Various Treatment plans for Lymphoma

If you have indolent non-Hodgkin lymphoma without symptoms, you may not need treatment for the cancer right away. The doctor watches your health closely so that treatment can start when you begin to have symptoms. Not getting cancer treatment right away is called watchful waiting.
If you have indolent lymphoma with symptoms, you will probably receive chemotherapy and biological therapy. Radiation therapy may be used for people with Stage I or Stage II lymphoma.
If you have aggressive lymphoma, the treatment is usually chemotherapy and biological therapy. Radiation therapy also may be used.
If non-Hodgkin lymphoma comes back after treatment, doctors call this a relapse or recurrence. People with lymphoma that comes back after treatment may receive high doses of chemotherapy, radiation therapy, or both, followed by stem cell transplantation.
You may want to know about side effects and how treatment may change your normal activities. Because chemotherapy and radiation therapy often damage healthy cells and tissues, side effects are common. Side effects may not be the same for each person, and they may change from one treatment session to the next. Before treatment starts, your health care team will explain possible side effects and suggest ways to help you manage them.
At any stage of the disease, you can have supportive care. Supportive care is treatment to control pain and other symptoms, to relieve the side effects of therapy, and to help you cope with the feelings that a diagnosis of cancer can bring.
You may want to talk to your doctor about taking part in a clinical trial, a research study of new treatment methods.

Treatment choices for Non-Hodgkin Lymphoma

Your doctor can describe your treatment choices and the expected results. You and your doctor can work together to develop a treatment plan that meets your needs.
Your doctor may refer you to a specialist, or you may ask for a referral. Specialists who treat non-Hodgkin lymphoma include hematologists, medical oncologists, and radiation oncologists. Your doctor may suggest that you choose an oncologist who specializes in the treatment of lymphoma. Often, such doctors are associated with major academic centers. Your health care team may also include an oncology nurse and a registered dietitian.
The choice of treatment depends mainly on the following:

• The type of non-Hodgkin lymphoma (for example, follicular lymphoma)
• Its stage (where the lymphoma is found)
• How quickly the cancer is growing (whether it is indolent or aggressive lymphoma)
• Your age
• Whether you have other health problems

Basis of the Staging Process with Lymphoma cells

The stage is based on where lymphoma cells are found (in the lymph nodes or in other organs or tissues). The stage also depends on how many areas are affected. The stages of non-Hodgkin lymphoma are as follows:

• Stage I: The lymphoma cells are in one lymph node group (such as in the neck or underarm). Or, if the abnormal cells are not in the lymph nodes, they are in only one part of a tissue or organ (such as the lung, but not the liver or bone marrow).
• Stage II: The lymphoma cells are in at least two lymph node groups on the same side of (either above or below) the diaphragm.  Or, the lymphoma cells are in one part of an organ and the lymph nodes near that organ (on the same side of the diaphragm). There may be lymphoma cells in other lymph node groups on the same side of the diaphragm.
• Stage III: The lymphoma is in lymph nodes above and below the diaphragm. It also may be found in one part of a tissue or an organ near these lymph node groups.
• Stage IV: Lymphoma cells are found in several parts of one or more organs or tissues (in addition to the lymph nodes). Or, it is in the liver, blood, or bone marrow.
• Recurrent: The disease returns after treatment.

In addition to these stage numbers, your doctor may also describe the stage as A or B:

• A: You have not had weight loss, drenching night sweats, or fevers.
• B: You have had weight loss, drenching night sweats, or fevers.

Staging of Non-Hodgkin Lymphoma to plan the best treatment

Your doctor needs to know the extent (stage) of non-Hodgkin lymphoma to plan the best treatment. Staging is a careful attempt to find out what parts of the body are affected by the disease.
Lymphoma usually starts in a lymph node. It can spread to nearly any other part of the body. For example, it can spread to the liver, lungs, bone, and bone marrow.
Staging may involve one or more of the following tests:

• Bone marrow biopsy: The doctor uses a thick needle to remove a small sample of bone and bone marrow from your hipbone or another large bone. Local anesthesia can help control pain. A pathologist looks for lymphoma cells in the sample.
• CT scan: An x-ray machine linked to a computer takes a series of detailed pictures of your head, neck, chest, abdomen, or pelvis. You may receive an injection of contrast material. Also, you may be asked to drink another type of contrast material. The contrast material makes it easier for the doctor to see swollen lymph nodes and other abnormal areas on the x-ray.
• MRI: Your doctor may order MRI pictures of your spinal cord, bone marrow, or brain. MRI uses a powerful magnet linked to a computer. It makes detailed pictures of tissue on a computer screen or film.
• Ultrasound: An ultrasound device sends out sound waves that you cannot hear. A small hand-held device is held against your body. The waves bounce off nearby tissues, and a computer uses the echoes to create a picture. Tumors may produce echoes that are different from the echoes made by healthy tissues. The picture can show possible tumors.
• Spinal tap: The doctor uses a long, thin needle to remove fluid from the spinal column. Local anesthesia can help control pain. You must lie flat for a few hours afterward so that you don't get a headache. The lab checks the fluid for lymphoma cells or other problems.
• PET scan: You receive an injection of a small amount of radioactive sugar. A machine makes computerized pictures of the sugar being used by cells in your body. Lymphoma cells use sugar faster than normal cells, and areas with lymphoma look brighter on the pictures.

Before having a Biopsy

You may want to ask your doctor these questions before having a biopsy:

• How will the biopsy be done?
• Where will I have my biopsy?
• Will I have to do anything to prepare for it?
• How long will it take? Will I be awake? Will it hurt?
• Are there any risks? What are the chances of swelling, infection, or bleeding after the biopsy?
• How long will it take me to recover?
• How soon will I know the results? Who will explain them to me?
• If I do have cancer, who will talk to me about next steps? When?

If you have swollen lymph nodes

If you have swollen lymph nodes or another symptom that suggests non-Hodgkin lymphoma, your doctor will try to find out what's causing the problem. Your doctor may ask about your personal and family medical history.
You may have some of the following exams and tests:

• Physical exam: Your doctor checks for swollen lymph nodes in your neck, underarms, and groin. Your doctor also checks for a swollen spleen or liver.
• Blood tests: The lab does a complete blood count to check the number of white blood cells. The lab also checks for other cells and substances, such as lactate dehydrogenase (LDH). Lymphoma may cause a high level of LDH.
• Chest x-rays: You may have x-rays to check for swollen lymph nodes or other signs of disease in your chest.
• Biopsy: A biopsy is the only sure way to diagnose lymphoma. Your doctor may remove an entire lymph node (excisional biopsy) or only part of a lymph node (incisional biopsy). A thin needle (fine needle aspiration) usually cannot remove a large enough sample for the pathologist to diagnose lymphoma. Removing an entire lymph node is best. The pathologist uses a microscope to check the tissue for lymphoma cells.

Types of Non-Hodgkin Lymphoma

When lymphoma is found, the pathologist reports the type. There are many types of lymphoma. The most common types are diffuse large B-cell lymphoma and follicular lymphoma.
Lymphomas may be grouped by how quickly they are likely to grow:

• Indolent (also called low-grade) lymphomas grow slowly. They tend to cause few symptoms.
• Aggressive (also called intermediate-grade and high-grade) lymphomas grow and spread more quickly. They tend to cause severe symptoms. Over time, many indolent lymphomas become aggressive lymphomas.

It's a good idea to get a second opinion about the type of lymphoma that you have. The treatment plan varies by the type of lymphoma. A pathologist at a major referral center can review your biopsy

Symptoms of Non-Hodgkin lymphoma

Non-Hodgkin lymphoma can cause many symptoms:

• Swollen, painless lymph nodes in the neck, armpits, or groin
• Unexplained weight loss
• Fever
• Soaking night sweats
• Coughing, trouble breathing, or chest pain
• Weakness and tiredness that don't go away
• Pain, swelling, or a feeling of fullness in the abdomen

Most often, these symptoms are not due to cancer. Infections or other health problems may also cause these symptoms. Anyone with symptoms that do not go away within 2 weeks should see a doctor so that problems can be diagnosed and treated.

Risk Factors for Non-Hodgkin Lymphoma

Doctors seldom know why one person develops non-Hodgkin lymphoma and another does not. But research shows that certain risk factors increase the chance that a person will develop this disease.
In general, the risk factors for non-Hodgkin lymphoma include the following:

• Weakened immune system: The risk of developing lymphoma may be increased by having a weakened immune system (such as from an inherited condition or certain drugs used after an organ transplant).
• Certain infections:Having certain types of infections increases the risk of developing lymphoma. However, lymphoma is not contagious. You cannot catch lymphoma from another person. The following are the main types of infection that can increase the risk of lymphoma:
  • Human immunodeficiency virus (HIV): HIV is the virus that causes AIDS. People who have HIV infection are at much greater risk of some types of non-Hodgkin lymphoma.
  • Epstein-Barr virus (EBV): Infection with EBV has been linked to an increased risk of lymphoma. In Africa, EBV infection is linked to Burkitt lymphoma.
  • Helicobacter pylori: H. pylori are bacteria that can cause stomach ulcers. They also increase a person's risk of lymphoma in the stomach lining.
  • Human T-cell leukemia/lymphoma virus type 1 (HTLV-1): Infection with HTLV-1 increases a person's risk of lymphoma and leukemia.
  • Hepatitis C virus: Some studies have found an increased risk of lymphoma in people with hepatitis C virus. More research is needed to understand the role of hepatitis C virus.
• Age: Although non-Hodgkin lymphoma can occur in young people, the chance of developing this disease goes up with age. Most people with non-Hodgkin lymphoma are older than 60. (For information about this disease in children, call the NCI's Cancer Information Service at 1-800-4-CANCER.)

Researchers are studying obesity and other possible risk factors for non-Hodgkin lymphoma. People who work with herbicides or certain other chemicals may be at increased risk of this disease. Researchers are also looking at a possible link between using hair dyes before 1980 and non-Hodgkin lymphoma.
Having one or more risk factors does not mean that a person will develop non-Hodgkin lymphoma. Most people who have risk factors never develop cancer.

Non-Hodgkin Lymphoma Cells

Non-Hodgkin lymphoma begins when a lymphocyte (usually a B cell) becomes abnormal. The abnormal cell divides to make copies of itself. The new cells divide again and again, making more and more abnormal cells. The abnormal cells don't die when they should. They don't protect the body from infections or other diseases. The buildup of extra cells often forms a mass of tissue called a growth or tumor.

What Is Non-Hodgkin Lymphoma?

Non-Hodgkin lymphoma is cancer that begins in cells of the immune system. The immune system fights infections and other diseases.
The lymphatic system is part of the immune system. The lymphatic system includes the following:

• Lymph vessels: The lymphatic system has a network of lymph vessels. Lymph vessels branch into all the tissues of the body.
• Lymph: The lymph vessels carry clear fluid called lymph. Lymph contains white blood cells, especially lymphocytes such as B cells and T cells.
• Lymph nodes: Lymph vessels are connected to small, round masses of tissue called lymph nodes. Groups of lymph nodes are found in the neck, underarms, chest, abdomen, and groin. Lymph nodes store white blood cells. They trap and remove bacteria or other harmful substances that may be in the lymph.
• Other parts of the lymphatic system: Other parts of the lymphatic system include the tonsils, thymus, and spleen. Lymphatic tissue is also found in other parts of the body including the stomach, skin, and small intestine.

For more information about potential donors and transplant centers

The National Marrow Donor Program® (NMDP), a nonprofit organization, manages the world’s largest registry of more than 11 million potential donors and cord blood units. The NMDP operates Be The Match®, which helps connect patients with matching donors.
A list of U.S. transplant centers that perform allogeneic transplants can be found at BeTheMatch.org/access. The list includes descriptions of the centers, their transplant experience, and survival statistics, as well as financial and contact information.

Organization:	National Marrow Donor Program
Address:	Suite 100 3001 Broadway Street, NE. Minneapolis, MN 55413–1753
Telephone:	612–627–5800 1–800–627–7692 (1–800–MARROW–2) (Be The Match Registry) 1–888–999–6743 (Be The Match Patient Services)
E-mail:	patientinfo@nmdp.org
Website:	http://www.bethematch.org

What are the costs of donating bone marrow, PBSCs, or umbilical cord blood?

All medical costs for the donation procedure are covered by Be The Match®, or by the patient’s medical insurance, as are travel expenses and other non-medical costs. The only costs to the donor might be time taken off from work.
A woman can donate her baby’s umbilical cord blood to public cord blood banks at no charge. However, commercial blood banks do charge varying fees to store umbilical cord blood for the private use of the patient or his or her family.

How do patients cover the cost of BMT or PBSCT?

Advances in treatment methods, including the use of PBSCT, have reduced the amount of time many patients must spend in the hospital by speeding recovery. This shorter recovery time has brought about a reduction in cost. However, because BMT and PBSCT are complicated technical procedures, they are very expensive. Many health insurance companies cover some of the costs of transplantation for certain types of cancer. Insurers may also cover a portion of the costs if special care is required when the patient returns home.
There are options for relieving the financial burden associated with BMT and PBSCT. A hospital social worker is a valuable resource in planning for these financial needs. Federal government programs and local service organizations may also be able to help.
NCI’s Cancer Information Service (CIS) can provide patients and their families with additional information about sources of financial assistance at 1–800–422–6237 (1–800–4–CANCER). NCI is part of the National Institutes of Health.

What is a “tandem transplant”?

A “tandem transplant” is a type of autologous transplant. This method is being studied in clinical trials for the treatment of several types of cancer, including multiple myeloma and germ cell cancer. During a tandem transplant, a patient receives two sequential courses of high-dose chemotherapy with stem cell transplant. Typically, the two courses are given several weeks to several months apart. Researchers hope that this method can prevent the cancer from recurring (coming back) at a later time.

What is a “mini-transplant”?

A “mini-transplant” (also called a non-myeloablative or reduced-intensity transplant) is a type of allogeneic transplant. This approach is being studied in clinical trials for the treatment of several types of cancer, including leukemia, lymphoma, multiple myeloma, and other cancers of the blood.
A mini-transplant uses lower, less toxic doses of chemotherapy and/or radiation to prepare the patient for an allogeneic transplant. The use of lower doses of anticancer drugs and radiation eliminates some, but not all, of the patient’s bone marrow. It also reduces the number of cancer cells and suppresses the patient’s immune system to prevent rejection of the transplant.
Unlike traditional BMT or PBSCT, cells from both the donor and the patient may exist in the patient’s body for some time after a mini-transplant. Once the cells from the donor begin to engraft, they may cause the GVT effect and work to destroy the cancer cells that were not eliminated by the anticancer drugs and/or radiation. To boost the GVT effect, the patient may be given an injection of the donor’s white blood cells. This procedure is called a “donor lymphocyte infusion.”

The possible side effects of BMT and PBSCT

The major risk of both treatments is an increased susceptibility to infection and bleeding as a result of the high-dose cancer treatment. Doctors may give the patient antibiotics to prevent or treat infection. They may also give the patient transfusions of platelets to prevent bleeding and red blood cells to treat anemia. Patients who undergo BMT and PBSCT may experience short-term side effects such as nausea, vomiting, fatigue, loss of appetite, mouth sores, hair loss, and skin reactions.
Potential long-term risks include complications of the pretransplant chemotherapy and radiation therapy, such as infertility (the inability to produce children); cataracts (clouding of the lens of the eye, which causes loss of vision); secondary (new) cancers; and damage to the liver, kidneys, lungs, and/or heart.
With allogeneic transplants, GVHD sometimes develops when white blood cells from the donor (the graft) identify cells in the patient’s body (the host) as foreign and attack them. The most commonly damaged organs are the skin, liver, and intestines. This complication can develop within a few weeks of the transplant (acute GVHD) or much later (chronic GVHD). To prevent this complication, the patient may receive medications that suppress the immune system. Additionally, the donated stem cells can be treated to remove the white blood cells that cause GVHD in a process called “T-cell depletion.” If GVHD develops, it can be very serious and is treated with steroids or other immunosuppressive agents. GVHD can be difficult to treat, but some studies suggest that patients with leukemia who develop GVHD are less likely to have the cancer come back. Clinical trials are being conducted to find ways to prevent and treat GVHD.
The likelihood and severity of complications are specific to the patient’s treatment and should be discussed with the patient’s doctor.

What happens after the stem cells have been transplanted to the patient?

After entering the bloodstream, the stem cells travel to the bone marrow, where they begin to produce new white blood cells, red blood cells, and platelets in a process known as “engraftment.” Engraftment usually occurs within about 2 to 4 weeks after transplantation. Doctors monitor it by checking blood counts on a frequent basis. Complete recovery of immune function takes much longer, however—up to several months for autologous transplant recipients and 1 to 2 years for patients receiving allogeneic or syngeneic transplants. Doctors evaluate the results of various blood tests to confirm that new blood cells are being produced and that the cancer has not returned. Bone marrow aspiration (the removal of a small sample of bone marrow through a needle for examination under a microscope) can also help doctors determine how well the new marrow is working.

Are any special measures taken when the cancer patient is also the donor (autologous transplant)?

The stem cells used for autologous transplantation must be relatively free of cancer cells. The harvested cells can sometimes be treated before transplantation in a process known as “purging” to get rid of cancer cells. This process can remove some cancer cells from the harvested cells and minimize the chance that cancer will come back. Because purging may damage some healthy stem cells, more cells are obtained from the patient before the transplant so that enough healthy stem cells will remain after purging.

How does the patient receive the stem cells during the transplant?

After being treated with high-dose anticancer drugs and/or radiation, the patient receives the stem cells through an intravenous (IV) line just like a blood transfusion. This part of the transplant takes 1 to 5 hours.

Are any risks associated with donating PBSCs?

Apheresis usually causes minimal discomfort. During apheresis, the person may feel lightheadedness, chills, numbness around the lips, and cramping in the hands. Unlike bone marrow donation, PBSC donation does not require anesthesia. The medication that is given to stimulate the mobilization (release) of stem cells from the marrow into the bloodstream may cause bone and muscle aches, headaches, fatigue, nausea, vomiting, and/or difficulty sleeping. These side effects generally stop within 2 to 3 days of the last dose of the medication.

Are any risks associated with donating bone marrow?

Because only a small amount of bone marrow is removed, donating usually does not pose any significant problems for the donor. The most serious risk associated with donating bone marrow involves the use of anesthesia during the procedure.
The area where the bone marrow was taken out may feel stiff or sore for a few days, and the donor may feel tired. Within a few weeks, the donor’s body replaces the donated marrow; however, the time required for a donor to recover varies. Some people are back to their usual routine within 2 or 3 days, while others may take up to 3 to 4 weeks to fully recover their strength.

How are umbilical cord stem cells obtained for transplantation?

Stem cells also may be retrieved from umbilical cord blood. For this to occur, the mother must contact a cord blood bank before the baby’s birth. The cord blood bank may request that she complete a questionnaire and give a small blood sample.
Cord blood banks may be public or commercial. Public cord blood banks accept donations of cord blood and may provide the donated stem cells to another matched individual in their network. In contrast, commercial cord blood banks will store the cord blood for the family, in case it is needed later for the child or another family member.
After the baby is born and the umbilical cord has been cut, blood is retrieved from the umbilical cord and placenta. This process poses minimal health risk to the mother or the child. If the mother agrees, the umbilical cord blood is processed and frozen for storage by the cord blood bank. Only a small amount of blood can be retrieved from the umbilical cord and placenta, so the collected stem cells are typically used for children or small adults.

How are PBSCs obtained for transplantation?

The stem cells used in PBSCT come from the bloodstream. A process called apheresis or leukapheresis is used to obtain PBSCs for transplantation. For 4 or 5 days before apheresis, the donor may be given a medication to increase the number of stem cells released into the bloodstream. In apheresis, blood is removed through a large vein in the arm or a central venous catheter (a flexible tube that is placed in a large vein in the neck, chest, or groin area). The blood goes through a machine that removes the stem cells. The blood is then returned to the donor and the collected cells are stored. Apheresis typically takes 4 to 6 hours. The stem cells are then frozen until they are given to the recipient.

How is bone marrow obtained for transplantation?

The stem cells used in BMT come from the liquid center of the bone, called the marrow. In general, the procedure for obtaining bone marrow, which is called “harvesting,” is similar for all three types of BMTs (autologous, syngeneic, and allogeneic). The donor is given either general anesthesia, which puts the person to sleep during the procedure, or regional anesthesia, which causes loss of feeling below the waist. Needles are inserted through the skin over the pelvic (hip) bone or, in rare cases, the sternum (breastbone), and into the bone marrow to draw the marrow out of the bone. Harvesting the marrow takes about an hour.
The harvested bone marrow is then processed to remove blood and bone fragments. Harvested bone marrow can be combined with a preservative and frozen to keep the stem cells alive until they are needed. This technique is known as cryopreservation. Stem cells can be cryopreserved for many years.

How are the donor’s stem cells matched to the patient’s stem cells?

To minimize potential side effects, doctors most often use transplanted stem cells that match the patient’s own stem cells as closely as possible. People have different sets of proteins, called human leukocyte-associated (HLA) antigens, on the surface of their cells. The set of proteins, called the HLA type, is identified by a special blood test.
In most cases, the success of allogeneic transplantation depends in part on how well the HLA antigens of the donor’s stem cells match those of the recipient’s stem cells. The higher the number of matching HLA antigens, the greater the chance that the patient’s body will accept the donor’s stem cells. In general, patients are less likely to develop a complication known as graft-versus-host disease (GVHD) if the stem cells of the donor and patient are closely matched.
Close relatives, especially brothers and sisters, are more likely than unrelated people to be HLA-matched. However, only 25 to 35 percent of patients have an HLA-matched sibling. The chances of obtaining HLA-matched stem cells from an unrelated donor are slightly better, approximately 50 percent. Among unrelated donors, HLA-matching is greatly improved when the donor and recipient have the same ethnic and racial background. Although the number of donors is increasing overall, individuals from certain ethnic and racial groups still have a lower chance of finding a matching donor. Large volunteer donor registries can assist in finding an appropriate unrelated donor.
Because identical twins have the same genes, they have the same set of HLA antigens. As a result, the patient’s body will accept a transplant from an identical twin. However, identical twins represent a small number of all births, so syngeneic transplantation is rare.

What types of cancer are treated with BMT and PBSCT?

BMT and PBSCT are most commonly used in the treatment of leukemia and lymphoma. They are most effective when the leukemia or lymphoma is in remission (the signs and symptoms of cancer have disappeared). BMT and PBSCT are also used to treat other cancers such as neuroblastoma (cancer that arises in immature nerve cells and affects mostly infants and children) and multiple myeloma. Researchers are evaluating BMT and PBSCT in clinical trials (research studies) for the treatment of various types of cancer.

Why are BMT and PBSCT used in cancer treatment?

One reason BMT and PBSCT are used in cancer treatment is to make it possible for patients to receive very high doses of chemotherapy and/or radiation therapy. To understand more about why BMT and PBSCT are used, it is helpful to understand how chemotherapy and radiation therapy work.
Chemotherapy and radiation therapy generally affect cells that divide rapidly. They are used to treat cancer because cancer cells divide more often than most healthy cells. However, because bone marrow cells also divide frequently, high-dose treatments can severely damage or destroy the patient’s bone marrow. Without healthy bone marrow, the patient is no longer able to make the blood cells needed to carry oxygen, fight infection, and prevent bleeding. BMT and PBSCT replace stem cells destroyed by treatment. The healthy, transplanted stem cells can restore the bone marrow’s ability to produce the blood cells the patient needs.
In some types of leukemia, the graft-versus-tumor (GVT) effect that occurs after allogeneic BMT and PBSCT is crucial to the effectiveness of the treatment. GVT occurs when white blood cells from the donor (the graft) identify the cancer cells that remain in the patient’s body after the chemotherapy and/or radiation therapy (the tumor) as foreign and attack them.

What are bone marrow transplantation and peripheral blood stem cell transplantation?

Bone marrow transplantation (BMT) and peripheral blood stem cell transplantation (PBSCT) are procedures that restore stem cells that have been destroyed by high doses of chemotherapy and/or radiation therapy. There are three types of transplants:

• In autologous transplants, patients receive their own stem cells.
• In syngeneic transplants, patients receive stem cells from their identical twin.
• In allogeneic transplants, patients receive stem cells from their brother, sister, or parent. A person who is not related to the patient (an unrelated donor) also may be used

Bone Marrow Transplantation

• Bone marrow transplantation and peripheral blood stem cell transplantation are procedures that restore stem cells that were destroyed by high doses of chemotherapy and/or radiation therapy.
• After being treated with high-dose anticancer drugs and/or radiation, the patient receives the harvested stem cells, which travel to the bone marrow and begin to produce new blood cells.
• A “mini-transplant” uses lower, less toxic doses of chemotherapy and/or radiation to prepare the patient for transplant.
• A “tandem transplant” involves two sequential courses of high-dose chemotherapy and stem cell transplant.
• The National Marrow Donor Program® operates Be The Match®, which provides patient support and maintains an international registry of volunteer stem cell donors.

Is there any research that shows palliative care is beneficial?

Yes. Research shows that palliative care and its many components are beneficial to patient and family health and well-being. A number of studies in recent years have shown that patients who have their symptoms controlled and are able to communicate their emotional needs have a better experience with their medical care. Their quality of life and physical symptoms improve. 
In addition, the Institute of Medicine 2007 report Cancer Care for the Whole Patient cites many studies that show patients are less able to adhere to their treatment and manage their illness and health when physical and emotional problems are present. To view this report, go to http://www.iom.edu/Reports/2007/Cancer-Care-for-the-Whole-Patient-Meeting-Psychosocial-Health-Needs.aspx 
Furthermore, patients who have serious illnesses and receive palliative care consultations have lower hospital costs than those who don’t. These consultations help determine treatment priorities and, therefore, help patients avoid unnecessary tests and procedures. (For more information, go to http://www.cancer.gov/ncicancerbulletin/NCI_Cancer_Bulletin_090908/page3 )

How do people talk about palliative care or decide what they need?

Patients and their loved ones should ask their doctor about palliative care. In addition to discussing their needs for symptom relief and emotional support, patients and their families should consider the amount of communication they need. What people want to know about their diagnosis and care varies with each person. It’s important for patients to tell their doctor about what they want to know, how much information they want, and when they want to receive it.

The issues that are addressed in Palliative Care

Palliative care can address a broad range of issues, integrating an individual’s specific needs into care. The physical and emotional effects of cancer and its treatment may be very different from person to person. For example, differences in age, cultural background, or support systems may result in very different palliative care needs.
 Comprehensive palliative care will take the following issues into account for each patient:

• Physical.  Common physical symptoms include pain, fatigue, loss of appetite, nausea, vomiting, shortness of breath, and insomnia. Many of these can be relieved with medicines or by using other methods, such as nutrition therapy, physical therapy, or deep breathing techniques. Also, chemotherapy, radiation therapy, or surgery may be used to shrink tumors that are causing pain and other problems.
  
• Emotional and coping.  Palliative care specialists can provide resources to help patients and families deal with the emotions that come with a cancer diagnosis and cancer treatment. Depression, anxiety, and fear are only a few of the concerns that can be addressed through palliative care. Experts may provide counseling, recommend support groups, hold family meetings, or make referrals to mental health professionals.
  
• Practical.  Cancer patients may have financial and legal worries, insurance questions, employment concerns, and concerns about completing advance directives. For many patients and families, the technical language and specific details of laws and forms are hard to understand. To ease the burden, the palliative care team may assist in coordinating the appropriate services. For example, the team may direct patients and families to resources that can help with financial counseling, understanding medical forms or legal advice, or identifying local and national resources, such as transportation or housing agencies. 
  
• Spiritual.  With a cancer diagnosis, patients and families often look more deeply for meaning in their lives. Some find the disease brings them more faith, whereas others question their faith as they struggle to understand why cancer happened to them. An expert in palliative care can help people explore their beliefs and values so that they can find a sense of peace or reach a point of acceptance that is appropriate for their situation.

Where do cancer patients receive and find a place that offers palliative care?

Cancer centers and hospitals often have palliative care specialists on staff. They may also have a palliative care team that monitors and attends to patient and family needs. Cancer centers may also have programs or clinics that address specific palliative care issues, such as lymphedema, pain management, sexual functioning, or psychosocial issues.
A patient may also receive palliative care at home, either under a physician’s care or through hospice, or at a facility that offers long-term care.
Patients should ask their doctor for the names of palliative care and symptom management specialists in the community. A local hospice may be able to offer referrals as well. Area hospitals or medical centers can also provide information. In addition, some national organizations have specific databases for referrals. For example, the Center to Advance Palliative Care has a list of providers by state at http://www.getpalliativecare.org/providers. The National Hospice and Palliative Care Organization’s Web site also has a list of providers at http://www.nhpco.org

The difference between palliative care and hospice

Although hospice care has the same principles of comfort and support, palliative care is offered earlier in the disease process. As noted above, a person’s cancer treatment continues to be administered and assessed while he or she is receiving palliative care. Hospice care is a form of palliative care that is given to a person when cancer therapies are no longer controlling the disease. It focuses on caring, not curing. When a person has a terminal diagnosis (usually defined as having a life expectancy of 6 months or less) and is approaching the end of life, he or she might be eligible to receive hospice care.

When is palliative care used and who gives it in cancer care?

Palliative care is given throughout a patient’s experience with cancer. It should begin at diagnosis and continue through treatment, follow-up care, and the end of life.
Although any medical professional may provide palliative care by addressing the side effects and emotional issues of cancer, some have a particular focus on this type of care. A palliative care specialist is a health professional who specializes in treating the symptoms, side effects, and emotional problems experienced by patients. The goal is to maintain the best possible quality of life.
Often, palliative care specialists work as part of a multidisciplinary team to coordinate care. This palliative care team may consist of doctors, nurses, registered dieticians, pharmacists, and social workers. Many teams include psychologists or a hospital chaplain as well. Palliative care specialists may also make recommendations to primary care physicians about the management of pain and other symptoms. People do not give up their primary care physician to receive palliative care.

What is palliative care?

Palliative care is care given to improve the quality of life of patients who have a serious or life-threatening disease, such as cancer. The goal of palliative care is to prevent or treat, as early as possible, the symptoms and side effects of the disease and its treatment, in addition to the related psychological, social, and spiritual problems. The goal is not to cure. Palliative care is also called comfort care, supportive care, and symptom management.

Palliative Care in Cancer

• Palliative care is comfort care given to a patient who has a serious or life-threatening disease, such as cancer, from the time of diagnosis and throughout the course of illness. It is usually provided by a specialist who works with a team of other health care professionals, such as doctors, nurses, registered dieticians, pharmacists, and social workers.
• Palliative care is different from hospice care. Although they share the same principles of comfort and support, palliative care begins at diagnosis and continues during cancer treatment and beyond.
• Hospitals, cancer centers, and long-term care facilities provide palliative care. Patients may also receive it at home. Physicians and local hospitals can provide the names of palliative care or symptom management specialists.
• Palliative care addresses the emotional, physical, practical, and spiritual issues of cancer. Family members may also receive palliative care.
• Research shows that palliative care improves the quality of life of patients and family members, as well as the physical and emotional symptoms of cancer and its treatment.

The targeted therapies that have been approved for specific types of cancer

The FDA has approved targeted therapies for the treatment of some patients with the following types of cancer (some targeted therapies have been approved to treat more than one type of cancer):
Adenocarcinoma of the stomach or gastroesophageal junction: Trastuzumab (Herceptin®)
Basal cell carcinoma: Vismodegib (Erivedge™)
Brain cancer: Bevacizumab (Avastin®), Everolimus (Afinitor®)
Breast cancer: Everolimus (Afinitor®), tamoxifen, toremifene (Fareston®), Trastuzumab (Herceptin®), fulvestrant (Faslodex®), anastrozole (Arimidex®), exemestane (Aromasin®), lapatinib (Tykerb®), letrozole (Femara®), pertuzumab (Perjeta™), ado-trastuzumab emtansine (Kadcyla™)
Colorectal cancer: Cetuximab (Erbitux®), Panitumumab (Vectibix®), Bevacizumab (Avastin®), Ziv-aflibercept (Zaltrap®), Regorafenib (Stivarga®)
Dermatofibrosarcoma protuberans: Imatinib mesylate (Gleevec®)
Head and neck cancer: Cetuximab (Erbitux®)
Gastrointestinal stromal tumor: Imatinib mesylate (Gleevec®), Sunitinib (Sutent®), Regorafenib (Stivarga®)
Giant cell tumor of the bone: Denosumab (Xgeva®)
Kaposi sarcoma: Alitretinoin (Panretin®)
Kidney cancer: Bevacizumab (Avastin®), Sorafenib (Nexavar®), Sunitinib (Sutent®), Pazopanib (Votrient®), Temsirolimus (Torisel®), Everolimus (Afinitor®), Axitinib (Inlyta®)
Leukemia: Tretinoin (Vesanoid®), Imatinib mesylate (Gleevec®), Dasatinib (Sprycel®), Nilotinib (Tasigna®), Bosutinib (Bosulif®), Rituximab (Rituxan®), Alemtuzumab (Campath®), Ofatumumab (Arzerra®), Obinutuzumab (Gazyva™)
Liver cancer: Sorafenib (Nexavar®)
Lung cancer: Bevacizumab (Avastin®), Crizotinib (Xalkori®), Erlotinib (Tarceva®), Gefitinib (Iressa®), Afatinib dimaleate (Gilotrif®), Ceritinib (LDK378/Zykadia) 
Lymphoma: Tositumomab and 131I-tositumomab (Bexxar®), Ibritumomab tiuxetan (Zevalin®), Denileukin diftitox (Ontak®), Brentuximab vedotin (Adcetris®), Rituximab (Rituxan®), Vorinostat (Zolinza®), Romidepsin (Istodax®), Bexarotene (Targretin®), Bortezomib (Velcade®), Pralatrexate (Folotyn®), Lenaliomide (Revlimid®), Ibrutinib (Imbruvica™), Siltuximab (Sylvant™)
Melanoma: Ipilimumab (Yervoy®), Vemurafenib (Zelboraf®), Trametinib (Mekinist®), Dabrafenib (Tafinlar®)
Multiple myeloma: Bortezomib (Velcade®), Carfilzomib (Kyprolis®), Lenaliomide (Revlimid®), Pomalidomide (Pomalyst®)
Myelodysplastic/myeloproliferative disorders: Imatinib mesylate (Gleevec®)
Pancreatic cancer: Erlotinib (Tarceva®), Everolimus (Afinitor®), Sunitinib (Sutent®)
Prostate cancer: Cabazitaxel (Jevtana®), Enzalutamide (Xtandi®), Abiraterone acetate (Zytiga®), Radium 223 chloride (Xofigo®)
Soft tissue sarcoma: Pazopanib (Votrient®)
Stomach cancer: Ramucirumab (Cyramza™)
Systemic mastocytosis: Imatinib mesylate (Gleevec®)
Thyroid cancer: Cabozantinib (Cometriq™), Vandetanib (Caprelsa®), Sorafenib (Nexavar®)

The side effects of Targeted cancer therapies

Scientists had expected that targeted cancer therapies would be less toxic than traditional chemotherapy drugs because cancer cells are more dependent on the targets than are normal cells. However, targeted cancer therapies can have substantial side effects.
The most common side effects seen with targeted therapies are diarrhea and liver problems, such as hepatitis and elevated liver enzymes.  Other side effects seen with targeted therapies include:

• Skin problems (acneiform rash, dry skin, nail changes, hair depigmentation)
• Problems with blood clotting and wound healing
• High blood pressure
• Gastrointestinal perforation (a rare side effect of some targeted therapies)

Certain side effects of some targeted therapies have been linked to better patient outcomes.  For example, patients who develop acneiform rash (skin eruptions that resemble acne) while being treated with the signal transduction inhibitors erlotinib (Tarceva®) or gefitinib (Iressa®), both of which target the epidermal growth factor receptor, have tended to respond better to these drugs than patients who do not develop the rash. Similarly, patients who develop high blood pressure while being treated with the angiogenesis inhibitor bevacizumab generally have had better outcomes.
The few targeted therapies that are approved for use in children can have different side effects in children than in adults, including immunosuppression and impaired sperm production.

Are there limitations with targeted cancer therapies?

Targeted therapies do have some limitations. One is that cancer cells can become resistant to them. Resistance can occur in two ways: the target itself changes through mutation so that the targeted therapy no longer interacts well with it, and/or the tumor finds a new pathway to achieve tumor growth that does not depend on the target.
For this reason, targeted therapies may work best in combination. For example, a recent study found that using two therapies that target different parts of the cell signaling pathway that is altered in melanoma by the BRAF V600E mutation slowed the development of resistance and disease progression to a greater extent  than using just one targeted therapy (1).  
Another approach is to use a targeted therapy in combination with one or more traditional chemotherapy drugs. For example, the targeted therapy trastuzumab (Herceptin®) has been used in combination with docetaxel, a traditional chemotherapy drug, to treat women with metastatic breast cancer that overexpresses the protein HER2/neu.
Another limitation of targeted therapy at present is that drugs for some identified targets are difficult to develop because of the target’s structure and/or the way its function is regulated in the cell. One example is Ras, a signaling protein that is mutated in as many as one-quarter of all cancers (and in the majority of certain cancer types, such as pancreatic cancer). To date, it has not been possible to develop inhibitors of Ras signaling with existing drug development technologies. However, promising new approaches are offering hope that this limitation can soon be overcome.

How is it determined whether a patient is a candidate for targeted therapy?

For some types of cancer, most patients with that cancer will have an appropriate target for a particular targeted therapy and, thus, will be candidates to be treated with that therapy. CML is an example: most patients have the BCR-ABL fusion gene. For other cancer types, however, a patient’s tumor tissue must be tested to determine whether or not an appropriate target is present. The use of a targeted therapy may be restricted to patients whose tumor has a specific gene mutation that codes for the target; patients who do not have the mutation would not be candidates because the therapy would have nothing to target.
Sometimes, a patient is a candidate for a targeted therapy only if he or she meets specific criteria (for example, their cancer did not respond to other therapies, has spread, or is inoperable). These criteria are set by the FDA when it approves a specific targeted therapy.

The types of Targeted Therapies that are available

Many different targeted therapies have been approved for use in cancer treatment. These therapies include hormone therapies, signal transduction inhibitors, gene expression modulator, apoptosis inducer, angiogenesis inhibitor, immunotherapies, and toxin delivery molecules.

• Hormone therapies slow or stop the growth of hormone-sensitive tumors, which require certain hormones to grow. Hormone therapies act by preventing the body from producing the hormones or by interfering with the action of the hormones. Hormone therapies have been approved for both breast cancer and prostate cancer.
• Signal transduction inhibitors block the activities of molecules that participate in signal transduction, the process by which a cell responds to signals from its environment. During this process, once a cell has received a specific signal, the signal is relayed within the cell through a series of biochemical reactions that ultimately produce the appropriate response(s). In some cancers, the malignant cells are stimulated to divide continuously without being prompted to do so by external growth factors. Signal transduction inhibitors interfere with this inappropriate signaling.
• Gene expression modulators modify the function of proteins that play a role in controlling gene expression.
• Apoptosis inducers cause cancer cells to undergo a process of controlled cell death called apoptosis. Apoptosis is one method the body uses to get rid of unneeded or abnormal cells, but cancer cells have strategies to avoid apoptosis. Apoptosis inducers can get around these strategies to cause the death of cancer cells.
• Angiogenesis inhibitors block the growth of new blood vessels to tumors (a process called tumor angiogenesis). A blood supply is necessary for tumors to grow beyond a certain size because blood provides the oxygen and nutrients that tumors need for continued growth. Treatments that interfere with angiogenesis may block tumor growth. Some targeted therapies that inhibit angiogenesis interfere with the action of vascular endothelial growth factor (VEGF), a substance that stimulates new blood vessel formation. Other angiogenesis inhibitors target other molecules that stimulate new blood vessel growth. 
• Immunotherapies trigger the immune system to destroy cancer cells. Some immunotherapies are monoclonal antibodies that recognize specific molecules on the surface of cancer cells. Binding of the monoclonal antibody to the target molecule results in the immune destruction of cells that express that target molecule. Other monoclonal antibodies bind to certain immune cells to help these cells better kill cancer cells.
• Monoclonal antibodies that deliver toxic molecules can cause the death of cancer cells specifically. Once the antibody has bound to its target cell, the toxic molecule that is linked to the antibody—such as a radioactive substance or a poisonous chemical—is taken up by the cell, ultimately killing that cell. The toxin will not affect cells that lack the target for the antibody—i.e., the vast majority of cells in the body.

Cancer vaccines and gene therapy are sometimes considered targeted therapies because they interfere with the growth of specific cancer cells.