Acute Myeloid Leukemia (AML)

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Acute Myeloid Leukemia (AML): Fast Facts

• Acute myeloid leukemia (AML) is the most common type of blood cancer in adults. If untreated, this form of leukemia usually progresses quickly.
• Acute myeloid leukemia also goes by other names, including acute myelogenous leukemia, acute myeloblastic leukemia, acute granulocytic leukemia, and acute nonlymphocytic leukemia.
• In a healthy person, bone marrow makes the blood stem cells that mature into infection-fighting white blood cells, oxygen-carrying red blood cells and blood-clotting platelets. When a person has AML, cells called myeloid stem cells usually develop instead into a type of immature white blood cell called myeloblasts, which never go on to become healthy, infection-fighting white blood cells.
• Sometimes in AML, too many stem cells also develop into abnormal red blood cells or platelets. When these abnormal, or leukemia, cells build up in the bone marrow and blood, there is less room for healthy white blood cells, red blood cells, and platelets, which may lead to infection, anemia, or easy bleeding. The leukemia cells can spread outside the blood to other parts of the body, including the brain, skin and gums.

Read more about leukemia treatment at the Seattle Cancer Care Alliance. »

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Acute Myeloid Leukemia (AML): Some of Our Key Research

The Hutchinson Center is recognized worldwide as one of the leading institutions involved in the research and treatment of acute myeloid leukemia. Center researchers pioneered bone-marrow transplantation, which is still considered one of the most effective leukemia treatments, and have trained doctors from around the world in this practice.

Thanks to a variety of clinical trials at the Seattle Cancer Care Alliance, of which the Hutchinson Center is a key collaborator, AML patients have access to the most promising treatments available.

The SCCA's transplantation record continues to receive top marks. It is one of only two transplant programs nationwide that consistently outperformed the expected one-year survival rate for unrelated donor transplants, according to an independent report that assessed 122 transplant centers over a five-year period beginning in 2002. Learn more. »

Pioneering bone-marrow transplantation
One of the Hutchinson Center's founders, Dr. E. Donnall Thomas, won the Nobel Prize in 1990 for his groundbreaking work in bone-marrow transplantation, one of the greatest success stories in cancer treatment.

Since then, Center investigators have trained physicians around the world in this procedure, and many new advances have occurred.

Read more about the Hutchinson Center's transplantation work. »

Pioneering targeted AML chemotherapy
Dr. Irwin Bernstein and colleagues discovered a key antibody that was instrumental in the development of Mylotarg®, which in 2000 became the first FDA-approved drug in a class of anticancer therapy called antibody-targeted chemotherapy.

In Mylotarg, a highly specific antibody recognizes a cell-surface molecule called CD33 that is abundant on AML cells but absent from normal blood stem cells. As a result, Mylotarg selectively destroys leukemic blast cells with an extremely potent chemotherapy agent, known as calicheamicin, while sparing the cells responsible for replenishing normal blood cells. Learn more. »

Making transplantation less toxic

• In the late 1990s, Dr. Rainer Storb and colleagues pioneered the development of a radically different approach to bone-marrow transplantation that offers hope for older or otherwise medically unfit blood-cancer patients whose bodies cannot withstand the rigors of a conventional transplant.
  
  Unlike traditional bone-marrow transplantation, this treatment—called the non-myeloablative stem-cell transplant or "mini" transplant—does not wipe out bone marrow and involves minimal doses of radiation. That means patients do not lose their hair or experience severe nausea or other side effects, and the procedure typically can be performed without a hospital stay. Learn more. »

Listen to a Webcast with Dr. Rainer Storb. »

• Since then, a significant 2007 study by Dr. Marco Mielcarek and colleagues found that lymphoma, leukemia and other blood-cancer patients who underwent these lower-intensity transplants experienced similar outcomes regardless of whether they received stem cells from a tissue-matched relative or an unrelated donor. The finding was significant because historically, researchers had observed a link between conventional bone-marrow transplants from unrelated donors and decreased overall survival rates for those patients. Learn more. »

Investigating new sources of transplantation cells
About one-third of all blood-cancer patients whose best curative treatment option is bone-marrow transplantation are unable to find a tissue-matched donor. One alternative is receiving a transplant that uses umbilical cord blood, which is rich in blood stem cells and can be collected without risk from the umbilical cord after birth of a child.

A major advantage of this source of cells for bone-marrow transplantation is that it does not need to be as well tissue-matched, allowing those patients who can not find a conventional donor to undergo transplantation. The major disadvantage is the small number of cells available from the cord blood. Learn more. »

Listen to a Webcast with Dr. Colleen Delaney. »

Seeking more effective chemotherapy regimens
Our researchers have a considerable interest in developing new treatment options for patients with untreated AML, AML that has reappeared after an initial remission, or AML that has yet to enter complete remission. Such patients typically aren’t candidates for blood stem-cell transplantation and may do poorly with standard therapies, making alternative regimens necessary. Here's a glimpse of some of the work we're doing in this area:

• The principal study for patients older than age 60 with untreated AML focuses on treatment using a combination of the anticancer drugs Mylotarg and vorinostat. Research led by Dr. Roland Walter has shown that vorinostat may increase the sensitivity of AML blasts to Mylotarg, thereby boosting the drug's effectiveness against the disease. Walter is also investigating other chemotherapy agents that can better "differentiate" AML blasts in the blood, making those cancer cells more sensitive to existing chemotherapy drugs.

• Research led by Dr. John Pagel has led to development of a more effective treatment regimen for newly-diagnosed AML patients younger than age 60 who are considered to have a "secondary" form of the disease—that is, they have already received chemotherapy for another condition or an earlier blood disorder, such as myelodysplasia.
  
  These results are important for the approximately one-third of AML patients under 60 who fall into that category because they tend not to respond well to standard therapies and are routinely ineligible for clinical trials that test new therapies. The study suggested that a mix of the chemotherapy agents mitoxantrone and cytarabine (Ara-C) and the experimental drug flavopiridol sent those AML patients' disease into complete remission at a far higher rate than would be expected from standard therapy.

Delivering targeted radiation to destroy cancer cells
Although previous studies have found that whole-body radiation prior to transplantation can significantly reduce the risk of AML's return, high-dose radiation also causes significant transplant-related deaths among the largely elderly AML patient population.

Drs. John Pagel, Fred Appelbaum and colleagues are testing new ways to deliver radiation in a targeted way, via antibodies that specifically bind to leukemia cells but not to healthy cells. Their hope is to reduce relapse rates while minimizing the toxic effects of radiation to normal organs, such as lung, liver, kidney and mucous membranes. Early results have suggested targeted therapies can achieve that goal. Learn more. »

Unlocking secrets to AML's growth
Research by Dr. Steven Collins has suggested that interfering with an active enzyme called CaMKIIy , which has been found to serve an important function in controlling the growth of myeloid leukemia cells, could slow or halt the production of the leukemia cells, potentially offering new hope for patients with AML. To generate a widely effective therapy, researchers would ideally need to find a way to block the active form of the enzyme, which would prevent immature blood cells from proliferating and instead coax them toward becoming normal, mature cells.

Fortifying the body against leukemia
Dr. Stanley Riddell and colleagues have been investigating use of a treatment technique for leukemia called immunotherapy—that is, harnessing the body's own infection-fighting T-cells against the disease. T-cells, however, typically die quickly, resulting in an interruption in immune response that could cause cancer to return. Through advanced testing, Riddell and colleagues found that one type of T-cell—central memory cells—had the staying power they were seeking. The approach holds promise for treating several types of cancer, including chemotherapy-resistant ALL in children. Learn more. »

Giving a second chance to children with AML
A second stem-cell transplant can improve the odds of curing children with aggressive AML whose cancer returns after a first transplant, according to Hutchinson Center research. Dr. Soheil Meshinchi and colleagues found that nearly half of the 25 children who received a second transplant were still alive and cancer-free 10 years after the study. Learn more. »

Determining quality of life after transplantation

• Many patients who undergo bone-marrow or stem-cell transplantation face a decline in mental skill and physical coordination after treatment, but a 2004 study by Dr. Karen Syrjala and colleagues has shown that these effects are largely temporary and that most patients can expect a return to normal function within a year of their transplant. A more recent analysis showed that most patients show even further improvement in brain function between one and five years after transplant. Learn more. »

• Another study led by Syrjala found that survivors of stem-cell transplantation for blood cancers can expect to be just about as healthy 10 years later as adults who have never had a transplant. The study found that transplant survivors and people who hadn’t had transplants reported similar rates of hospitalization and outpatient medical visits. They also had similar rates of diseases and conditions such as asthma, diabetes, high blood pressure, high cholesterol, osteoporosis and hypothyroidism, along with similar psychological health, marital satisfaction and employment. It is, however, very important for transplant survivors to get regular primary care and health monitoring in the years after transplant. Learn more. »

Listen to a Webcast with Dr. Karen Syrjala. »

Find out more about our leukemia investigators:
Fred Appelbaum » William Bensinger » Irwin Bernstein » Paul Carpenter » Bruce Clurman » Steven Collins » Joachim Deeg » Colleen Delaney » Matthew Fero » Mary Flowers » Ted Gooley » Ajay Gopal » John Hansen » Shelly Heimfeld » Kenneth Kopecky » Wendy Leisenring » Michael Linenberger »	Paul Martin » Soheil Meshinchi » Marco Mielcarek » John Pagel » Stephen Petersdorf » Oliver Press » Jerald Radich » Jean Sanders » Brenda Sandmaier » Andrei Shustov » Derek Stirewalt » Rainer Storb » Barry Storer » Karen Syrjala » Edus "Hootie" Warren » Ann Woolfrey »

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Acute Myeloid Leukemia (AML): More Resources

• Every advance in cancer treatment in recent years has come out of clinical trials that test innovative medical approaches on patients.Find out more about clinical trials on acute myeloid leukemia. »

• The Hutchinson Center also conducts ongoing cancer-prevention studies that depend on participation of healthy volunteers. Learn more about getting involved in research studies. » 

• In need of medical attention for acute myeloid leukemia? Visit the Seattle Cancer Care Alliance to get help. »

• The Hutchinson Center is on a mission to eliminate cancer and related diseases as causes of human suffering and death, and you can help. Make a gift today. »

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