Cancer Helper

Frequent follow-up exams are needed for many years after treatment for aplastic anemia is finished. These follow-up visits are very important. The doctors will continue to watch your blood counts for signs of recurrent disease, as well as for short-term and long-term side effects of treatment. You should report any new symptoms to the doctor right away so that a relapse or side effects can be treated.

Health checkups include a careful physical examination and blood counts, as well as other necessary tests the doctor may want. If there is a return (relapse) of the aplastic anemia, it will usually happen in the first year after treatment. Another problem is that, occasionally, people with aplastic anemia are at increased risk for developing acute leukemia. It is useful to diagnose and treat leukemia as early as possible.

Another benefit of follow-up care is that it gives you a chance to discuss questions and concerns that can come up during and after your recovery.

It is important to have frank, open, and honest talks with your doctor. Your doctor and the rest of the health care team want to answer all of your questions. For instance, consider asking the following:

• Do you know what caused my aplastic anemia?
• What treatment choices do I have?
• Which treatment do you recommend, and why?
• What are the side effects to the treatments that you recommend?
• What can I do to help reduce the side effects I may have from the treatment?
• What are the chances that my aplastic anemia will come back once I am in remission?
• What is the outlook for my survival?

Many years ago, aplastic anemia was considered a fatal disease unless the patient recovered without treatment (spontaneously). Now that we understand this is an immune disease, treatments have been devised that have an 80% to 90% success rate. There are long-term side effects, such as graft-versus-host disease for those who receive stem cell transplants, but this affects only a minority of people.

The other major side effect is that a small number of people with aplastic anemia will develop leukemia or other cancers after several years. However, it isn?t clear that this is always caused by the treatment. It may be caused by a problem with the blood cells themselves.

Because the treatment of aplastic anemia is so specialized, treatment it may best be done at a major medical center where they have experience with this disease. This is particularly true for stem cell transplants.

Sometimes the first treatment isn’t successful and will need to be repeated. Often the second treatment will be effective, even if the first wasn’t. Also, the treatment may be only partially effective, and the blood counts may not return to normal. In this situation, many people can still lead a normal life and not need treatment. Their blood counts, although not normal, will be high enough for a normal life.

Sometimes, none of the treatments are successful. In this case a person with aplastic anemia might want to consider taking part in a clinical trial, that is, a study of a new therapy that hasn’t yet been proven successful.

The 2 forms of treatment for aplastic anemia are primary and supportive.

PrimaryTreatment

This treatment is directed toward curing the condition. If you are young, allogeneic stem cell transplantation is considered the best option (see the American Cancer Society document, “Bone Marrow and Peripheral Blood Stem Cell Transplants”). In this treatment you will first receive low doses of radiation therapy to your whole body and high doses of chemotherapy. Sometimes only chemotherapy is used. This works best in children and young adults. As people get older, they are less able to tolerate this procedure. Some doctors use age 35 as the cutoff.

Soon after the radiation and/or chemotherapy, you will receive a transfusion with blood-forming stem cells from a donor. The stem cells are obtained either by multiple bone marrow aspirations (while the donor is under general anesthesia) or by a procedure that uses a machine that separates blood cells taken from a large vein, removes the part of the blood containing most of the stem cells, and returns the other cells. This is called apheresis and it has become the most commonly used method. The stem cells are infused through your vein into the blood and then travel to the bone marrow, where they will grow. This treatment is successful about 60% of the time.

Your donor must have a similar “tissue type”(or be immunologically compatible) with you. Most often the best matched donor is a sister or brother. This “matching” is determined by testing in the laboratory. If a matched sister or brother is not available, then stem cells may be used from an unrelated donor or cells stored from umbilical cord blood. A nationwide registry of potential stem cell donors and stored umbilical cord blood has been developed (www.marrow.org).

If you are too old for a transplant or do not have a matched donor then doctors will recommend treatment that suppresses your immune system. Remember that it is your immune system that is probably causing the aplastic anemia.

The major drug that is used is called antithymocyte globulin (ATG). ATG is an antibody produced against human T lymphocytes, a special type of immune white blood cell. The T-lymphocytes are likely destroying the bone marrow stem cells. The ATG is made in either horses or rabbits and purified before being used.

This medicine is given by intravenous injection and decreases the function (suppresses) your immune system. Often a second drug called cyclosporine is added to suppress the immune system. The combination of the 2 treatments is successful about 60% of the time in patients with the most severe disease. This doesn’t mean that the aplastic anemia is cured 60% of the time. Rather some of the time, instead of becoming completely normal, the blood counts rise to a manageable level, which leaves the patient feeling well and able to live a normal life.

Both stem cell transplantation and immune suppression therapy have equal success rates — about 60% — but different side effects. With stem cell transplant patients, the major side effect is graft-versus-host disease. With ATG, the major problem is that after several years, about 15% of patients develop leukemia or a leukemia-like abnormality called myelodysplasia.

Supportive Treatment

While your blood counts are low, you may need transfusions of red blood cells. Since your blood platelets also will be low, you may need platelet transfusions. Because of your low white blood cell count, you may develop an infection and require treatment with antibiotics. Infection is the major cause of death from aplastic anemia. Treatment with antibiotics needs to be started as soon as infection is suspected. Treatment with white blood cell transfusions is not practical. It is not possible to get enough white blood cells from normal donors to raise a person’s white blood cell count.

Drugs can be given to increase the white blood cell count. These are called G-CSF (Neupogen) and GM-CSG (Sargramostim). These work only slightly for most patients with aplastic anemia.

Some patients will have only a mild form of aplastic anemia and can manage without either stem cell transplantation or ATG. Some of these patients can be managed with drugs called androgens. Androgens are male sex hormones that also stimulate blood production. They are the reason that men have higher red blood cell counts than do women. Although they can be effective in treating aplastic anemia, they create major side effects in women. They cause them to develop masculine characteristics such as facial hair growth, balding, deepening voice, etc.

Side Effects of Treatment

Stem cell transplantation is a major procedure with many risks and side effects. The most serious side effects occur during the first few weeks after the transplant. Some people may die during this procedure. With advances in this treatment, however, death from these early side effects is less common.

If you have a transplant, you will develop very low blood counts from the radiation therapy and/or chemotherapy and will need treatments such as red blood cell and platelet transfusions. You can develop nausea, vomiting, diarrhea, and mouth sores from the treatment. Serious infections are also likely to occur and are treated with large doses of antibiotics. These all generally go away in 3 to 4 weeks when the transplanted blood-forming stem cells start to produce normal blood cells. But during this wait, you must stay in the hospital.

Another possible side effect of a stem cell transplant is graft-versus-host disease. This occurs when the transplanted donor cells attack your own cells through an immune reaction. This can lead to skin rashes with severe itching and bowel disturbances such as diarrhea. The immune system is also blocked. Although graft-versus-host disease can be partly controlled with medicines, it can sometimes be very disabling and occasionally, fatal. It occurs more often in older patients, which is one reason to avoid transplants in this group.

The therapies that suppress the immune system (called immunosuppressive therapies) may also have side effects. ATG can cause allergic reactions while it is being given. These take the form of skin rashes or sometimes asthma-like breathing problems. Generally, these side effects can be controlled with medicines. Cyclosporine can damage your kidneys and liver, so if you are being treated with this drug you must be carefully watched. Blood tests will be done often to check kidney and liver function.

Clinical Trials

The purpose of clinical trials: Studies of promising new or experimental treatments in patients are known as clinical trials. A clinical trial is only done when there is some reason to believe that the treatment being studied may be valuable to the patient. Treatments used in clinical trials are often found to have real benefits. Researchers conduct studies of new treatments to answer the following questions:

• Is the treatment helpful?
• How does this new type of treatment work?
• Does it work better than other treatments already available?
• What side effects does the treatment cause?
• Are the side effects greater or less than the standard treatment?
• Do the benefits outweigh the side effects?
• In which patients is the treatment most likely to be helpful?

Types of clinical trials: There are 3 phases of clinical trials in which a treatment is studied before it is eligible for approval by the FDA (Food and Drug Administration).

Phase I clinical trials: The purpose of a phase I study is to find the best way to give a new treatment and how much of it can be given safely. The cancer care team watches patients carefully for any harmful side effects. The treatment has been well tested in lab and animal studies, but the side effects in patients are not completely known. Doctors conducting the clinical trial start by giving very low doses of the drug to the first patients and increasing the dose for later groups of patients until side effects appear. Although doctors are hoping to help patients, the main purpose of a phase I study is to test the safety of the drug.

Phase II clinical trials: These studies are designed to see if the drug works. Patients are given the highest dose that doesn’t cause severe side effects (determined from the phase I study) and closely observed for an effect on the cancer. The cancer care team also looks for side effects.

Phase III clinical trials: Phase III studies involve large numbers of patient ??? often several hundred. One group (the control group) receives the standard (most accepted) treatment. The other group receives the new treatment. All patients in phase III studies are closely watched. The study will be stopped if the side effects of the new treatment are too severe or if one group has had much better results than the others.

If you are in a clinical trial, you will have a team of experts taking care of you and monitoring your progress very carefully. The study is especially designed to pay close attention to you.

However, there are some risks. No one involved in the study knows in advance whether the treatment will work or exactly what side effects will occur. That is what the study is designed to find out. While most side effects disappear in time, some can be permanent or even life threatening. Keep in mind, though, that even standard treatments have side effects. Depending on many factors, you may decide to enroll in a clinical trial.

Deciding to enter a clinical trial: Enrollment in any clinical trial is completely up to you. Your doctors and nurses will explain the study to you in detail and will give you a form to read and sign indicating your desire to take part. This process is known as giving your informed consent. Even after signing the form and after the clinical trial begins, you are free to leave the study at any time, for any reason. Taking part in the study does not prevent you from getting other medical care you may need.

To find out more about clinical trials, ask your cancer care team. Among the questions you should ask are:

• Is there a clinical trial for which I would be eligible?
• What is the purpose of the study?
• What kinds of tests and treatments does the study involve?
• What does this treatment do? Has it been used before?
• Will I know which treatment I receive?
• What is likely to happen in my case with, or without, this new treatment?
• What are my other choices and their advantages and disadvantages?
• How could the study affect my daily life?
• What side effects can I expect from the study? Can the side effects be controlled?
• Will I have to be hospitalized? If so, how often and for how long?
• Will the study cost me anything? Will any of the treatment be free?
• If I am harmed as a result of the research, what treatment would I be entitled to?
• What type of long-term follow-up care is part of the study?
• Has the treatment been used to treat other types of cancers?

The American Cancer Society offers a clinical trials matching service for patients, their family, and friends. You can reach this service at 1-800-303-5691 or on our Web site at http://clinicaltrials.cancer.org. Based on the information you provide about your cancer type, stage, and previous treatments, this service can compile a list of clinical trials that match your medical needs. In finding a center most convenient for you, the service can also take into account where you live and whether you are willing to travel.

You can also get a list of current clinical trials by calling the National Cancer Institute’s Cancer Information Service toll free at 1-800-4-CANCER or by visiting the NCI clinical trials Web site at http://www.cancer.gov/clinicaltrials.

Complementary and Alternative Therapies

Complementary and alternative therapies are a diverse group of health care practices, systems, and products that are not part of usual medical treatment. They may include products such as vitamins, herbs, or dietary supplements, or procedures such as acupuncture, massage, and a host of other types of treatment. There is a great deal of interest today in complementary and alternative treatments for cancer. Many are now being studied to find out if they are truly helpful to people with cancer.

You may hear about different treatments from family, friends, and others, which may be offered as a way to treat your cancer or to help you feel better. Some of these treatments are harmless in certain situations, while others have been shown to cause harm. Most of them are of unproven benefit.

The American Cancer Society defines complementary medicine or methods as those that are used along with your regular medical care. If these treatments are carefully managed, they may add to your comfort and well-being. Alternative medicines are defined as those that are used instead of your regular medical care. Some of them have been proven not to be useful or even to be harmful, but are still promoted as ?cures.? If you choose to use these alternatives, they may reduce your chance of fighting your cancer by delaying, replacing, or interfering with regular cancer treatment.

Before changing your treatment or adding any of these methods, discuss this openly with your doctor or nurse. Some methods can be safely used along with standard medical treatment. Others, however, can interfere with standard treatment or cause serious side effects. That is why it’s important to talk with your doctor.

Signs and Symptoms of Aplastic Anemia

If you have aplastic anemia, you may have the following signs or symptoms:

• shortness of breath and fatigue, which is caused by anemia (too few red blood cells)
• serious infections because of not enough infection-fighting white blood cells (neutropenia/leukopenia)
• bruising or bleeding because of a shortage of platelets (thrombocytopenia)

Some people may not have any symptoms, but results of a routine blood test may suggest a diagnosis of aplastic anemia. There are other conditions in which blood formation may be abnormal. These are all considered when your doctor is determining your diagnosis.

Two tests are used to diagnose aplastic anemia. The first is a blood count, which confirms that the red cell count, white cell count, and platelet count are low. The next step is a bone marrow test, which includes an aspiration and a biopsy.

In bone marrow aspiration a small amount of liquid bone marrow (about 1 teaspoon) is sucked out with a thin needle and a syringe. During a bone marrow biopsy procedure, a small cylinder-shaped piece of bone and marrow (about 1/16 inch in diameter and 1/3 inch long) is removed with a slightly larger needle. Both samples usually are taken at the same time from the back of the pelvic bone.

The procedure is done with you lying on your stomach. The prominent part of the pelvic bone (about 2 inches to the side of the spine) and skin are numbed with local anesthetic. A small incision is made in the skin — about one-eighth inch. Then the biopsy needle is placed into the bone and a core of bone marrow removed. After that another needle, attached to a syringe, is placed into the marrow and marrow is sucked out. In spite of anesthesia, the procedure may still be uncomfortable, particularly when the marrow is sucked out.

Usually a pathologist, a doctor specializing in diagnosing disease by laboratory tests, examines the bone marrow under a microscope. A hematologist, internist who specializes in blood diseases, or a hematopathologist, pathologist who specializes in blood diseases, could also review the bone marrow sample. Finding an “empty” bone marrow, that is, one that lacks normal blood-producing cells, confirms the diagnosis. Leukemia or sometimes other kinds of cancers can also cause low blood counts, but in that case the bone marrow would be filled with leukemia or other cancer cells.

We know that certain chemicals such as benzene can cause aplastic anemia. Many chemotherapy drugs and radiation treatment can damage the bone marrow but usually don’t cause aplastic anemia. The most common causes are drugs and virus infections, particularly viral hepatitis. Environmental pollutants are another cause.

Doctors have tried to tie together how medicines, chemicals, and viruses can cause this disease. The most commonly accepted explanation is that these agents cause an abnormal immune reaction in the body. This immune reaction then somehow attacks and damages the bone marrow stem cells. This theory has led to the modern treatment of this disease, which has been very successful (see the section “How Is Aplastic Anemia Treated?”).

A risk factor is anything that increases your chance of getting a disease. For example, certain cancers have different risk factors. Exposing skin to strong sunlight is a risk factor for skin cancer. Smoking is a risk factor for cancers of the lung, mouth, larynx, bladder, kidney, colon, and several other organs. But having a risk factor, or even several, does not mean that you will get the disease.

We know that certain aplastic anemias are inherited. For acquired aplastic anemia, the major risk factors are medicines, virus infections, and chemicals. Many years ago, one drug, chloramphenicol, was associated with several cases of aplastic anemia. For that reason, it is no longer used in the United States. But it is still available in many other countries. Other medicines linked to aplastic anemia are:

• nonsteroidal medicines for pain and inflammation such as indomethacin (Indocin), piroxicam (Feldene), diclofenac (Voltaren)
• sulfonamides, a group of antibiotics used to treat bacterial infections
• antithyroid drugs such as propylthiouracil and methimazole (Tapazole)
• Furosemide (Lasix), a diuretic medicine used to help get rid of excess fluid in the body
• phenothiazines (Thorazine, Compazine), medicines used for nausea and certain psychiatric problems
• Allopurinol (Zyloprim), used for treating gout
• Ticlopidine — used to prevent strokes and heart attacks

This is only a list of the drugs most often associated with aplastic anemia. Other drugs may also cause this disease. The best way to avoid aplastic anemia from drugs is to take medicines only if they are necessary.

Exposure to chemicals such as solvents and pesticides is also a risk factor. This can occur either in the home or in the workplace.

Aplastic anemia is a rare disease, occurring in only 1 to 2 persons for every million in the United States. That means somewhere between 300 and 600 new cases each year. It affects people of all ages and all races. It is more common in developing countries, perhaps because there is more exposure to toxic chemicals.

Aplastic anemia is a disorder in which the bone marrow fails to make blood cells. The bone marrow is the soft, inner part of bones where the 3 types of blood cells are made:

• red blood cells, which carry oxygen to the tissues from the lungs
• white blood cells, which fight infection
• platelets, which seal damaged blood vessels to prevent bleeding

These cells are made by blood-forming stem cells in the bone marrow. In aplastic anemia, the stem cells are damaged and there are very few of them. As a result, too few blood cells are produced. Rarely, just one of the cell lines, such as red cells, white cells, or platelets, is abnormal.

Aplastic anemia is not a type of cancer but may be associated with certain cancers (especially those affecting the bone marrow, such as leukemias) or cancer treatments. A small number of patients with aplastic anemia may develop leukemia.

There are 2 kinds of aplastic anemia, inherited and acquired. Acquired aplastic anemia is much more common than the inherited type.

Inherited Aplastic Anemia

The most common type of inherited aplastic anemia is called Fanconi Anemia.This is usually diagnosed in people when they are children or young adults. About half of patients with Fanconi anemia have other congenital problems such as growth retardation, small head size, absent thumbs, dark spots on the skin, and absence of 1 of the 2 bones in the forearm. There are several different gene abnormalities that can be inherited to cause Fanconi anemia. Some of these are linked to an increased risk for cancer. People with Fanconi anemia have a 50 times higher risk for other cancers, especially in the mouth and throat, esophagus, and leukemia.

The other kinds of inherited forms of aplastic anemia are much less common. One is called dyskeratosis congenita. People with this problem have abnormal skin pigmentation, abnormal finger nails, and white patches in their mouth (leukoplakia). This is very rare — only a few hundred patients are known worldwide. People with this problem also have a higher risk of developing cancers.

Another inherited cause of anemia is called the Diamond-Blackfan syndrome. In this situation, only red blood cell production is affected. A fourth disorder is the Shwachman-Diamond syndrome. Here, the major problem is poor production of white blood cells, although the other cell lines can occasionally be abnormal. In both of these, patients will often have other problems such as short stature and other bone abnormalities.

Acquired Aplastic Anemia

This usually occurs in adults, although children may also be affected. Most have no other abnormalities. But scientists have found that a few people with acquired aplastic anemia have an abnormality of genes responsible for keeping cell DNA intact. In most cases, the aplastic anemia is thought to be caused by a person’s reaction to some drug, chemical, or virus they were exposed to.

Important research into anal cancer is currently underway in many university hospitals, medical centers, and other institutions around the country. Each year, scientists find out more about what causes the disease, how to prevent it, and how to improve treatment.

Causes and prevention: Recent research has identified human papillomavirus (HPV) as a major factor in causing some types of anal cancer. It is beginning to show how HPV affects molecules inside anal cells to cause them to become cancerous.

Current research in this area includes development of vaccines to prevent HPV infection, thereby eliminating a cause of many anal cancers. Recently, a vaccine has been proven successful in preventing HPV 16 infection in women. The vaccine also prevents the development of precancerous changes in the cervix.

Improved understanding of the molecular changes inside anal cancer cells is expected to help scientists develop new drugs to fight this disease.

HIV treatment: The immune deficiency of people with HIV infections can lead to developing anal cancer. Newer drug treatments for HIV will prevent the development of immune deficiency for many years.

Early detection: Ongoing research is studying the value of screening tests for anal cancer, especially in people with major risk factors. Some doctors feel that anal cancer is similar in some ways to cervical cancer. Anal cytology, a procedure similar to the Pap test for cervical cancer, may be useful in early diagnosis of anal cancer and even in finding precancerous changes called anal intraepithelial neoplasia (AIN). In this test, cells are gently scraped from the lining layer of the anus and checked under a microscope. Work is also in progress to find a way of treating this problem and preventing cancer from developing.

Treatment: In the past few years, for example, evidence has grown showing the benefits of combining radiation with chemotherapy. This approach has reduced the number of surgeries needed for anal cancer, including the need for permanent colostomies.

New treatment combinations are being studied. For example, clinical trials that compare 5-FU plus mitomycin with 5-FU and cisplatin may conclude that cisplatin is more effective than mitomycin.

New radiosensitizing agents, agents that increase the effect of radiation therapy, are being developed for use as combined modality therapy in chemotherapy and radiation therapy clinical trials. These studies offer new hope for patients to benefit from these therapies and to have acceptable toxicities.

Doctors are learning more about how to deliver external radiation more accurately and effectively and decrease the effect on normal healthy tissues. Other research is being done to learn about the possible benefits of using both external radiation and interstitial (implanted) radiation therapy.