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Personal story about beating cancer


Living With Leukemia

by Carol Lewis (staff writer FDA Consumer)

It wasn't the flu-like symptoms that sent Neil Keller to the hospital one night in January 1995. It wasn't even the crippling back pain that left him virtually immobilized. It was the odd red stripe that Kathy Keller noticed running down the back of her husband's calf that prompted his sudden trip to the emergency room.

Following his evaluation, the physical education teacher from Frederick, Md., learned that the red stripe was a blood clot. He also learned that he had leukemia and needed immediate medical attention.

"I hastily left our two young children in the care of their grandparents because Neil was being transported quickly by ambulance to a special cancer center in Baltimore," remembers Kathy Keller. "It happened just that quickly."

According to the American Cancer Society (ACS), about 30,000 new cases of leukemia were diagnosed in the United States in 2001. And even though it is thought of primarily as a childhood disease, the ACS says that leukemia strikes more adults than children. Anyone can get it, and like many forms of cancer, its cause is unknown. Certain risk factors, such as genetic conditions or adverse environmental exposure, are believed to increase the chances of developing the disease.

Survival is strongly linked to age at diagnosis and the type of leukemia. Fortunately, the overall five-year survival rate for people with leukemia has tripled over the past 40 years. In 1960, the rate was 14 percent. By the 1970s, it had reached 35 percent. Today, the overall five-year survival rate is 44 percent.

All forms of leukemia can be treated. In the last decade, several new drugs or new uses for existing drugs have been approved by the Food and Drug Administration to treat various types of leukemia. One of the most recent of these approved drugs--Gleevec (imatinib mesylate)--represents a new strategy in fighting one type of leukemia. It works by blocking the rapid growth of white blood cells.

But cancer experts say the best hope of a breakthrough that will greatly improve cure rates and duration of remission lies in understanding and controlling the abnormal molecular processes that lead to the development of all types of leukemia.

More Than One Disease

Leukemia is cancer of the blood cells. It is characterized by the uncontrolled growth of developing bone marrow cells. It is not a single disease, but a group of malignancies in which the bone marrow and blood-forming organs produce excessive numbers of white blood cells. White blood cells develop from a type of cell in the bone marrow called a stem cell. When the process of white cell maturation goes awry, leukemia results. Immature white cells prevent the normal production of all blood cells, including white blood cells, which fight infection. In most leukemias, an increased number of cancerous white blood cells are produced, causing the lymph nodes, liver, or spleen to enlarge.

Leukemias are classified by the type of white blood cell that has abnormal growth and by how fast the disease is progressing. Acute leukemia can be fatal within weeks or months without aggressive treatment. Abnormal blood cells that remain very immature, called "blasts," increase rapidly and the disease worsens quickly.

Chronic leukemia may produce no symptoms for years. Some immature cells may be present, but in general, these cells are more mature than those in acute leukemia and are able to carry out some normal cell functions. The number of blasts increases less rapidly than in acute leukemia, and as a result, chronic leukemia worsens gradually. Chronic leukemia can become acute leukemia.

Leukemia can arise in either of the two main types of white blood cells--lymphoid or myeloid. Leukemia that affects lymphoid cells is known as lymphocytic leukemia. When myeloid cells are affected, the disease is called myelogenous leukemia. The disease can be categorized into one of four main types shown below, depending on whether it is acute or chronic and myelogenous or lymphocytic.

While both children and adults can develop leukemia, certain types are more common in one age group than in another. However, Keller was diagnosed with acute lymphocytic leukemia (ALL), which is most prevalent among children, at age 31. Although he died less than a year later, Kathy Keller says that at the time the prognosis for people with ALL seemed good. "They said it was critical, sure--that Neil's condition was life-threatening," she remembers, "but we got lucky that the attending physician turned out to be someone who recognized the urgency in getting Neil immediate medical attention."

In addition to the four main types, there are sub-types of leukemia, such as acute promyelocytic leukemia (APL), and hairy cell--a chronic leukemia in which the abnormal white blood cells appear to be covered with tiny hairs when viewed under a microscope.

Symptoms of Leukemia

Some people with leukemia may not experience any symptoms at all and their first inkling of a problem could be the results of a routine blood test. Others, however, may complain of flu-like symptoms such as fatigue, fever, weight loss, and night sweats. Other signs of leukemia can include:

  • easy bruising or bleeding
  • lymph node enlargement
  • bone pain
  • swelling of the abdomen due to an enlarged liver and spleen
  • increased susceptibility to infection


Common blood tests, such as the complete blood cell count (CBC), as well as blood cell examination under a microscope, can provide the first evidence that a person has leukemia. Most people with acute leukemia, like Keller, will have an increased number of white blood cells, not enough red blood cells, and not enough platelets.

"Neil's white blood counts were as high as his doctor had ever seen," says Kathy Keller. "But he also indicated that Neil's type of leukemia had a 90 percent cure rate with a two-year treatment plan."

In addition to the CBC, a bone marrow test is frequently performed to confirm the diagnosis and determine the type of leukemia. Bone marrow is the soft, spongy tissue in the center of the bones that produces the white blood cells, red blood cells and platelets. Two kinds of tissue samples are taken for examination under a microscope and for special tests such as chromosomal analysis. In a procedure known as a bone marrow "aspiration," cells are withdrawn with a fine needle and syringe. A bone marrow "biopsy" involves taking a piece of bone with marrow inside, using a larger needle. Both samples usually are taken from the same site, generally on the back of the pelvic bone.

Other diagnostic tests could include:

  • removing and testing an entire lymph node
  • drawing fluid from the spinal cavity in the lower back (spinal tap)
  • measuring certain chemicals in the blood (to determine liver or kidney problems caused by leukemia or certain chemotherapy drugs)
  • using X-rays, computed tomography (CT) scans, magnetic resonance imaging (MRI), or ultrasound imaging, to obtain detailed images of internal organs.

Leukemia treatments

Many people died from leukemia--often within months of diagnosis--before the advent of effective treatments. Now, many more are cured (usually defined as five or more years of disease-free survival).

The goal in treating leukemia is to achieve complete remission (all signs and symptoms of leukemia have disappeared, although there still may be cancer in the body) by destroying cancerous cells so that normal cells can again grow in the bone marrow. In remission, cancerous cells cannot be seen in the blood or bone marrow, but more therapy is needed to achieve a cure. Several areas of research have yielded new approaches to treating leukemia. But the kind of treatment given and the outlook for a person with the disease vary greatly, according to the exact type of leukemia the person has, and other individual factors.

Chemotherapy refers to the use of drugs to kill cancer cells. It is the main treatment for nearly all types of leukemia. Most of these anticancer drugs are injected through a vein (IV injection or intravenously), but some can be taken by mouth. Either way, the drugs enter the bloodstream and spread throughout the body to kill cancerous cells.

Chemotherapy is given in cycles: a treatment period is followed by a recovery period. The process may be repeated. The duration of the treatment varies depending on the type of leukemia. Sometimes certain drugs are combined with others for a greater treatment effect. Unlike many people who show progress following chemotherapy, Keller periodically showed progress, but then relapsed.

"Neil responded well to chemotherapy for short periods of time," says Kathy Keller, "but he never went through a remission."

Most anticancer drugs are cytotoxic, which means they kill not only cancerous cells but also normal cells, particularly in the bone marrow. "The rationale of chemotherapy is that the normal cells are more likely to eventually survive the effects of chemotherapeutic agents than the cancer cells," says Amna Ibrahim, M.D., a medical officer in the FDA's Center for Drug Evaluation and Research.

New Treatments

Gleevec demonstrated in trials that it substantially reduces the level of cancerous cells in the bone marrow and blood of people with CML. A new class of drug to fight cancer, Gleevec is different from other cancer drugs because it specifically targets an enzyme that causes cells to become cancerous and multiply in people with CML. It works by blocking the protein product that is responsible for transforming normal cells into cancerous ones. Gleevec provided a new cancer treatment for chronic CML after the failure of interferon-alpha therapy, CML in blast crisis, and CML in an accelerated phase.

After two years of study, Gleevec, manufactured by Novartis Pharmaceuticals Corp., of East Hanover, N.J., appears to offer advantages over some other leukemia treatments: oral administration, tolerable side effects, and a high response rate.

The FDA's accelerated approval of Gleevec was based on the response rate observed in early clinical trials. Accelerated approval allows products for serious or life-threatening illnesses to reach the market sooner, based on clinical trials that have not yet demonstrated true clinical benefit, like survival or improved disease-related symptoms, but in which early results have indicated the drug is reasonably likely to have real clinical benefit.

James Foran, M.D., a medical oncologist at the University of Nebraska Medical Center and spokesman for the Leukemia and Lymphoma Society, says that CML occurs when pieces of two different chromosomes break off and reattach on the opposite chromosome, forming what's known as the "Philadelphia chromosome." This chromosome "translocation" leads to the enzyme being "turned on" all the time. As a result, potentially life-threatening levels of both mature and immature white blood cells occur in the bone marrow and the blood. "Gleevec shuts down the growth signals from the Philadelphia chromosome," says Foran, and blocks the rapid growth of malignant white blood cells.

But because the information from Gleevec clinical trials is still early, it is not known how durable the responses to this treatment will be. In fact, relapses following initial responses to Gleevec are now being reported.

Another class of drugs, known as differentiating agents, is used in treating APL. These drugs promote differentiation of the very immature leukemic white blood cells into more mature functioning cells. Two drugs in this class include Vesanoid (all-trans retinoic acid or ATRA), made by Hoffmann-La Roche Inc. of Nutley, N.J., which was approved by the FDA for first-line treatment, and Trisenox (arsenic trioxide), made by Cell Therapeutics Inc. of Seattle and approved for second-line therapy after ATRA treatment failure. These drugs have improved the prognosis of APL.

Mylotarg (gemtuzamab ozogamicin), another new type of leukemia drug, consists of an antibody against AML blast cells combined with a toxin to kill the cells. Mylotarg, manufactured by Wyeth-Ayerst Pharmaceuticals of St. Davids, Pa., the pharmaceutical branch of American Home Products Corp., was approved in May 2001 for treatment of elderly patients with AML who cannot tolerate more conventional chemotherapy.

Bone Marrow Transplants

Bone marrow transplants offer some people like 44-year-old Tom Kochanowicz of Omaha, Neb., the best chance of survival and, in his case, a cure. Kochanowicz was diagnosed with CML at age 38 when his doctor detected a lump in his side. "Fortunately," he says, "mine was the slow-moving kind and initially was managed with medications to bring my white blood cell count under control."

However, Kochanowicz says the side effects of the radiation and chemotherapy treatments took their toll. "The aggressive treatment was wiping out my immune system," he remembers. Consequently, despite hopes that the drug treatments would conquer, or at least manage, his leukemia, Kochanowicz admits he had always known that his life ultimately would depend on a bone marrow transplant.

In this procedure, existing abnormal bone marrow is eliminated through radiation treatments or chemotherapy. Healthy marrow is then injected directly into the bloodstream in a procedure similar to a blood transfusion. The bone marrow migrates to and takes root in the recipient's bones, and the cells begin to divide. It generally takes about three weeks and sometimes longer for the transplanted bone marrow to start producing white blood cells to protect against infections, making the procedure quite risky. Healthy marrow may have been supplied either by the patient in the early stage of the disease, or by a donor. Only someone who has a compatible tissue type--ideally a close relative--can be a donor.

Both of Kochanowicz's brothers were perfect blood matches, giving him excellent odds for a full recovery. As the result of a successful transplant, Kochanowicz is now entering his sixth year of remission. Keller wasn't as fortunate.

"We were told that brothers and sisters were the best matches," says Kathy Keller. "But since Neil was an only child, we tested the kids, me, and his parents." Keller's father ended up donating the needed bone marrow.

A parent or child is able to donate needed bone marrow only about 1 percent of the time, says Edwin P. Alyea, a medical oncologist with the Dana-Farber Cancer Institute in Boston. As in Keller's rare situation, Alyea says, "When they can, that's very lucky."

He also says that unrelated donor registries make it possible for people to have blood matches outside their families. These registries increase the chances of finding donors based on ethnic background and other specific qualifications. But Alyea says that "more minorities need to contribute to the registries" and greater outreach is needed in these communities.

A major complication of bone marrow transplants is graft-versus-host disease (GVHD) in which the transplanted marrow cells react against the patient's tissues; primarily the liver, the skin, and the digestive tract.

Despite surviving leukemia, Kochanowicz's last six years haven't been easy. His transplant experience included severe GVHD--for nearly two years he was unable to swallow, and a condition called scleroderma hardened the connective tissue in his skin.

Alyea explains that although a bone marrow transplant plays a key role in the treatment for certain types of leukemia, as a whole "it is basically an exchange of one disease for another. You're trading the disease itself, for which the treatment options and the chances of cure may be limited, for the possible complications of the transplant treatment," he says.

Alyea also says doctors have learned that patients who develop acute or chronic GVHD have a lower risk of the disease returning after the bone marrow transplant. "This demonstrates that the donor's immune system may play a role in cure," says Alyea. After a long and frustrating battle with the unpleasant effects of GVHD, Kochanowicz now manages his symptoms with medications, and admits that he feels better than he has "in a very long time."

Biologic Therapy

A relatively new addition to the family of cancer treatments is biological therapy (sometimes called immunotherapy). Biological therapy uses the body's immune system, either directly or indirectly, to fight cancer or to lessen the side effects that may be caused by some cancer treatments.

Patricia Keegan, M.D., a deputy division director in the FDA's Center for Biologics Evaluation and Research, explains that the immune system is a complex network of cells and organs that work together to defend the body against foreign invaders. This network is one of the body's main defenses against cancer. For example, the immune system may recognize the difference between healthy cells and cancerous cells in the body, and work to eliminate those that become cancerous.

Biological therapies, says Keegan, are designed to repair, stimulate, or enhance the immune system's responses when cancer prevents it from functioning adequately. Some immune system substances can be produced in the laboratory for use in cancer treatments. But Keegan says that, although biological drugs can be effective in treating different types of leukemia, there are so few available because "they are labor-intensive--the development of blood products is a relatively young field that is still developing."

The Future

Scientists are finding better ways to treat leukemia, and the chances of recovery keep improving. A physician who specializes in the treatment of leukemia is in the best position to discuss a person's prognosis and to offer the best course of treatment for a particular type of leukemia.

Survival rates may indicate how long groups of people may live. However, it's important to remember that statistics are averages based on large numbers of people. These numbers cannot be used to predict what will happen to an individual because no two people are identical, and treatments and responses vary.


Accelerated phase: The middle phase of chronic myeloid leukemia that lasts from six to 18 months. The white blood cell count increases as the disease is harder to control with conventional treatments.

Acute leukemia: A rapidly progressing cancer of the bone marrow and other blood-forming tissues.

Biological therapy (immunotherapy): Treatment to stimulate or restore the ability of the immune system to fight infection and disease.

Blasts: Immature blood cells.

Blast crisis: The final phase of chronic myeloid leukemia, lasting about three to six months.

Bone marrow: Soft, spongy tissue in the center of the bones that produces white blood cells, red blood cells, and platelets.

Bone marrow transplant: A procedure to replace bone marrow destroyed by treatment with high doses of anticancer drugs or radiation.

Catheter: A flexible tube used to deliver fluids into, or withdraw fluids from, the body.

Chemotherapy: Treatment with anticancer drugs.

Chromosome: The carrier of hereditary characteristics found in cells.

Chronic leukemia: A slowly progressing cancer of the blood-forming tissues.

Cure: Five or more years of disease-free survival.

Differentiating agents: A type of therapy that can trigger immature cells to become more mature and functional.

Donor: A person who donates organs, tissues, cells or other biological material.

First-line treatment: The drugs and other therapies given to a patient who is diagnosed with a disease and has not had any therapy for the disease.

Graft-versus-host disease (GVHD): A reaction of donated bone marrow against a person's tissue.

Immune system: The complex group of organs and cells that defends the body against infection or disease.

IV injection (intravenously): Injection into a vein.

Lymph node: A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue.

Lymphoid: Refers to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop.

Malignancy: Cancer.

Myeloid: Pertaining to, derived from, or manifesting certain features of the bone marrow. Also called myelogenous.

Oncologist: A doctor who specializes in treating cancer.

Platelets (thrombocytes): A type of blood cell that helps prevent bleeding by causing blood clots to form.

Red blood cells (erythrocytes): Cells that carry oxygen to all parts of the body.

Relapse: The return of signs and symptoms of cancer after a period of improvement.

Remission: A decrease in or disappearance of signs and symptoms of cancer. In partial remission, some, but not all, signs and symptoms disappear. In complete remission, all signs and symptoms have disappeared, although there could still be cancer in the body.

Second-line treatment: The drugs and other therapies given to a patient who has a disease that has either not responded to or recurs following first-line treatment.

Spleen: An organ that is part of the lymphatic system and produces lymphocytes, filters the blood, stores blood cells, and destroys old blood cells.

White blood cells (leukocytes): A type of cell in the immune system that helps the body fight infection and disease. White blood cells include lymphocytes, granulocytes, macrophages, and others.

The four main types of leukemia, common characteristics,
and their distribution among children and adults.

Acute lymphocytic leukemia (ALL)

  • Develops from cells in the bone marrow called lymphocytes
  • Accounts for slightly more than half of all cases of childhood leukemia
  • Most common cancer in children
  • Progresses rapidly

Chronic lymphocytic leukemia (CLL)

  • Develops from lymphocytes
  • Cells look mature but their function may not be normal
  • Occurs almost exclusively in adults
  • Most common leukemia in adults
  • Progresses slowly

Acute myelogenous leukemia (AML)

  • Also known as acute myeloid leukemia
  • Develops from either granulocytes or monocytes (types of white blood cells)
  • Affects children and adults
  • Accounts for just under half of childhood leukemia cases
  • Progresses rapidly

Chronic myelogenous leukemia (CML)

  • Another form of myeloid leukemia
  • Develops from granulocytes or monocytes
  • Affects adults
  • About half as common as CLL
  • Progresses slowly

Reprinted from FDA Consumer. This article originally appeared in the March-April 2003 FDA Consumer.


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