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Acute myeloid leukemia (AML) treatment in adults

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Acute myeloid leukemia (AML) treatment in adults
Author
Richard A Larson, MD
Section Editor
Bob Lowenberg, MD, PhD
Deputy Editor
Rebecca F Connor, MD
Last literature review version 19.3: Fri Sep 30 00:00:00 GMT 2011 | This topic last updated: Fri Oct 01 00:00:00 GMT 2010 (More)

ACUTE MYELOID LEUKEMIA OVERVIEW — Acute myeloid leukemia (AML) is a type of cancer of the blood. It affects a group of white blood cells called myeloid cells. Normally, myeloid and other blood cells are produced by the bone marrow (the spongy area in the middle of bones) in a controlled fashion. In someone with AML, the blood cell production process is abnormal and large numbers of immature myeloid cells are produced and may be released into the blood stream. Sometimes, the number of white blood cells in the circulation is abnormally high because of overproduction of malignant blood cells.

The overproduction of myeloid cells prevents the bone marrow from producing other important blood cells, including red blood cells, other types of white blood cells, and platelets. This results in a variety of body-wide symptoms, including anemia, bleeding, and an increased risk of infection.

GENERAL INFORMATION ABOUT ACUTE MYELOID LEUKEMIA TREATMENT — A number of chemotherapy medications are effective against AML. Studies are underway to find the best medicines, doses, and treatment schedules for AML.

Researchers have discovered that the genetic makeup of the abnormal myeloid cells can vary, which affects how you respond to treatment. Your treatment can be tailored based upon a careful analysis of your genetic material. Treatment of AML also depends upon your age (see ‘Acute myeloid leukemia treatment in older people’ below).

The usual treatment of AML is divided into two phases: induction of remission and postremission therapy.

INDUCTION OF REMISSION IN ACUTE MYELOID LEUKEMIA — The initial phase of treatment is referred to as remission induction or “induction” therapy. Induction therapy is given with the goal of decreasing the number of leukemia cells to an undetectable level and restoring the production of normal blood cells. Most of the cells in your body divide and multiply slowly and are not affected by chemotherapy. However, certain cells, such as those in the bone marrow (where the blood cells are produced), the hair follicles, and the lining of the gastrointestinal (GI) tract are multiplying rapidly. As a result, chemotherapy is most likely to cause side effects such as anemia (lowered red blood cell count), susceptibility to infection (lowered white blood cell count) and bleeding (lowered platelet count). Other side effects include temporary loss of hair, sores in the mouth, upset stomach, and diarrhea. (See “Induction therapy for acute myeloid leukemia in younger adults”.)

The most common remission induction regimens include cytarabine, given continuously for seven days through an intravenous (IV) line. An anthracycline, such as daunorubicin or idarubicin is given in a single IV dose for the first three days of treatment. This is sometimes known as the “7+3” regimen. These drugs kill AML cells over the first 7 to 14 days; it then takes the bone marrow about 14 days to recover and produce normal blood cells again.

This phase of treatment takes about four weeks and is almost always performed while you stay in the hospital. The induction phase usually consists of one or two cycles. A cycle of chemotherapy refers to the time it takes to give the drugs and the time required for the body to recover.

Induction therapy frequently results in a complete remission of the AML, meaning that there are no visible leukemia cells in the blood or bone marrow and that the bone marrow is functioning normally. However, such remissions are usually short-lived unless additional, postremission therapy is given.

POSTREMISSION THERAPY OF ACUTE MYELOID LEUKEMIA — Post-remission therapy is given with the intention of killing leukemia cells that can remain in the bone marrow or blood, but are undetectable under the microscope. (See “Post-remission therapy for acute myeloid leukemia in younger adults”.)

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There are three basic treatment choices for post-remission therapy: additional chemotherapy, stem cell transplantation from a donor (allogeneic stem cell transplantation), or stem cell transplantation using your own stem cells (autologous stem cell transplantation). The “best” postremission treatment depends upon several factors, including how aggressive the AML is:

 

  • People with favorable risk disease are usually advised to have chemotherapy.
  • People with unfavorable risk disease are usually advised to have an allogeneic stem cell transplantation.
  • The best treatment for intermediate risk disease is not clear; participation in a clinical trial is recommended, when possible. (See ‘Clinical trials’ below.)

 

Additional chemotherapy — Chemotherapy given after remission is called remission consolidation or postremission chemotherapy, and often includes high-dose cytarabine. Consolidation chemotherapy is usually given in the hospital monthly over several days. Consolidation chemotherapy is given for approximately three to four months.

Stem cell transplantation — Stem cell transplantation, also called bone marrow transplantation or hematopoietic cell transplantation, is a treatment in which you are given very high doses of chemotherapy or total body irradiation. This treatment is intended to kill cancer cells, but it also destroys all normal cells developing in the bone marrow. This means that your body’s normal source of critical blood components (ie, the bone marrow) is no longer functional.

After the treatment, you must have a healthy supply of young blood cells (called stem cells) reintroduced, or transplanted. The transplanted cells then reestablish the blood cell production process in the bone marrow. The new stem cells also generate a new immune system. (See “Patient information: Bone marrow transplantation (stem cell transplantation)”.)

Stem cell transplantation is not recommended for all patients with AML. Serious, and sometimes even fatal, complications occur more commonly with stem cell transplantation than with chemotherapy. In certain groups of people, there is no clear benefit of stem cell transplantation over chemotherapy. However, transplantation may be appropriate in some people, such as those with more aggressive forms of AML, those who have a relapse following remission, and those who do not achieve remission after initial induction therapy.

There are two main types of stem cell transplantation: allogeneic and autologous.

 

  • Allogeneic transplantation uses stem cells from a donor, ideally a sibling with a similar genetic makeup (called an HLA-matched related donor). The HLA genes are inherited from both parents and govern your immune system. If you do not have a sibling with similar genetic characteristics, an unrelated person with a similar genetic makeup may be used (called a matched unrelated donor). Other possibilities include the use of a sibling with partially similar genetic characteristics or stem cells collected from blood in a newborn’s umbilical cord.

    Allogeneic transplantation treats AML in two ways. First, high doses of chemotherapy or radiation are given immediately before the transplant, which aggressively attacks and kills the leukemia cells present in the blood and bone marrow. Second, when cells from another person are injected, the donor stem cells identify the leukemia cells as foreign and launch an immune attack that helps destroy any remaining leukemia cells. This is called the “graft versus leukemia” or “graft versus tumor” effect.

    Unfortunately, this response can lead to a complication called “graft versus host disease“, in which the immune response includes an attack on some of your own healthy organs. Symptoms can include severe skin rash, diarrhea, liver damage, and other problems. Still, allogeneic transplantation is preferred over autologous transplantation in people with AML.

  • In an autologous transplant, your own normal stem cells are collected while you are in complete remission, before the high dose chemotherapy or radiation is given. In some cases, the cells are treated to remove any lingering leukemia cells that may be present, although this is experimental. After the stem cells are collected, they are frozen for use at a later time. After your chemotherapy or radiation is complete, the harvested cells are thawed and returned by IV infusion.

    Because the transplanted stem cells do not come from another person, there is no “graft versus host” disease. This helps reduce some of the side effects of treatment, but in general it also makes autologous transplantation somewhat less effective than allogeneic transplantation in fighting the leukemia, because of the lack of a “graft versus leukemia” effect. Autologous transplantation less often recommended for treatment of AML for this reason.

 

Complete remission — The goal of AML treatment is to achieve a complete remission. Complete remission means that there is no visible evidence of leukemia cells in the blood or bone marrow and the bone marrow is functioning normally. A bone marrow biopsy and blood testing are done to determine when/if this occurs.

ACUTE MYELOID LEUKEMIA TREATMENT IN OLDER PEOPLE — In general, people over 60 years old do not respond as well to treatment for AML. This is related to the following factors:

 

  • Difficult-to-treat leukemia cells may be more common in older people. This means that the AML that occurs in older people tends to be more resistant to standard chemotherapy drugs.
  • In older people, the presence of other disorders, such as diabetes, kidney, lung, or heart disease, increases the risk of treatment-related complications.

 

Treatment decisions for older people with AML are best made on a case by case basis. In otherwise healthy older people, even those >75 years of age, whose leukemia is not “high-risk” according to genetic testing, induction chemotherapy is generally recommended. (See “Treatment of acute myeloid leukemia in older adults”.)

In older people with slowly progressing AML, severe underlying health problems, or high risk and unfavorable AML, the expected benefit of chemotherapy may not be worth the anticipated discomfort, hospitalization, and potentially toxic side effects. If the potential risk of chemotherapy is greater than the potential benefit, supportive care may be recommended. Supportive care generally includes blood transfusions for anemia and antibiotics as needed for infections.

Which treatment is right for me? — You and your family should get information from your healthcare provider about your type of AML, expected benefits of various treatments, possible side effects and toxicities, and your long-term outlook. These discussions are critical in determining the best course of action for you.

TREATMENT OF RELAPSED OR RESISTANT ACUTE MYELOID LEUKEMIA — A limited number of treatments are effective in the treatment of AML. Thus, if you do not respond or relapse after initial chemotherapy, management is more difficult:

 

  • Approximately 50 percent of people with long first remissions (greater than one year) benefit from a second induction attempt at remission with daunorubicin and cytarabine or with high-dose cytarabine (HDAC), but the duration of the second remission is usually shorter than the first. Because of this, stem cell transplantation should be considered for anyone who relapses after his or her initial treatment (once a second complete or partial remission is obtained).
  • People who relapse within 12 months of their initial diagnosis usually have AML with a high degree of drug resistance and therefore have a lower rate of achieving a second complete remission. Medicines specifically approved for use in patients with relapsed AML or experimental agents may be useful in this setting, followed by stem cell transplantation considered if a remission occurs.

 

More detailed information is available by subscription. (See “Treatment of relapsed or refractory acute myeloid leukemia”.)

LONG TERM MONITORING OF ACUTE MYELOID LEUKEMIA — Once you are in complete remission, you will need long term monitoring so that any relapse can be detected and treated. Relapse is most likely to occur within the first two years after induction chemotherapy, and becomes less common later.

Prognosis — Your chances of being cured of AML depend upon a number of factors, including your age, other health conditions, how aggressive your AML is, and whether you have been treated with chemotherapy before your AML diagnosis. In one study, approximately 65, 40, and 15 percent of people with favorable, intermediate, and unfavorable risk disease, respectively, were alive five years after diagnosis.

However, when discussing chances of cure, it is important to remember that these numbers represent averages and do not necessarily predict what will happen to you. A complete discussion of prognosis of AML is available separately. (See “Prognosis of acute myeloid leukemia”.)

CLINICAL TRIALS — Many patients with leukemia will be asked to enroll in a clinical (research) trial. A clinical trial is a carefully controlled way to study the effectiveness of new treatments or new combinations of known therapies. Ask your doctor for more information, or read about clinical trials at:

 

  • www.cancer.gov/clinicaltrials/
  • file://clinicaltrials.gov/

 

WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem.

This article will be updated as needed every four months on our web site (www.uptodate.com/patients).

Related topics for patients, as well as selected articles written for healthcare professionals, are also available. Some of the most relevant are listed below.

Patient Level Information:

Patient information: Bone marrow transplantation (stem cell transplantation)

Professional Level Information:

Clinical manifestations, pathologic features, and diagnosis of acute myeloid leukemia
Clinical manifestations, pathologic features, and diagnosis of acute promyelocytic leukemia in adults
Cytogenetics in acute myeloid leukemia
Induction therapy for acute myeloid leukemia in younger adults
Initial treatment of acute promyelocytic leukemia in adults
Molecular biology of acute promyelocytic leukemia
Molecular genetics of acute myeloid leukemia
Overview of the complications of acute myeloid leukemia
Pathogenesis of acute myeloid leukemia
Post-remission therapy for acute myeloid leukemia in younger adults
Prognosis of acute myeloid leukemia
Remission criteria in acute myeloid leukemia and monitoring for residual disease
Therapy-related myeloid neoplasms: Acute myeloid leukemia and myelodysplastic syndrome
Treatment of acute myeloid leukemia in older adults
Treatment of relapsed or refractory acute myeloid leukemia
Treatment of relapsed or refractory acute promyelocytic leukemia in adults

The following organizations also provide reliable health information.

 

  • National Library of Medicine

 

(www.nlm.nih.gov/medlineplus/healthtopics.html)

 

  • National Cancer Institute

 

(www.cancer.gov/cancertopics)

 

  • American Cancer Society

 

(www.cancer.org)

 

  • The Leukemia & Lymphoma Society

 

(www.leukemia-lymphoma.org)

 

  • National Marrow Donor Program

 

(www.marrow.org)

 

  • The American Society of Clinical Oncology

 

(www.cancer.net/portal/site/patient)

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REFERENCES

  1. Schiffer CA, Dodge R, Larson RA. Long-term follow-up of Cancer and Leukemia Group B studies in acute myeloid leukemia. Cancer 1997; 80:2210.
  2. Estey EH. Therapeutic options for acute myelogenous leukemia. Cancer 2001; 92:1059.
  3. Benjamin S, Kroll ME, Cartwright RA, et al. Haematologists’ approaches to the management of adolescents and young adults with acute leukaemia. Br J Haematol 2000; 111:1045.
  4. Cassileth PA, Harrington DP, Appelbaum FR, et al. Chemotherapy compared with autologous or allogeneic bone marrow transplantation in the management of acute myeloid leukemia in first remission. N Engl J Med 1998; 339:1649.
  5. Estey EH. How I treat older patients with AML. Blood 2000; 96:1670.
  6. Wahlin A, Markevärn B, Golovleva I, Nilsson M. Prognostic significance of risk group stratification in elderly patients with acute myeloid leukaemia. Br J Haematol 2001; 115:25.
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