Patient education: Acute myeloid leukemia (AML) treatment in adults (Beyond the Basics)

ACUTE MYELOID LEUKEMIA OVERVIEW — Acute myeloid leukemia (also called AML) is a cancer of the blood and bone marrow cells. It affects a group of white blood cells called myeloid cells because they are formed in the bone marrow. "Acute" means that it develops and advances quickly, and requires immediate treatment.

Normally, myeloid and other blood cells are produced in the bone marrow (the spongy area in the middle of bones) in a carefully regulated fashion. In someone with AML, this process is abnormal. Large numbers of immature and abnormal myeloid cells (called myeloblasts, or just "blasts") are produced, fill the bone marrow space, and are released into the bloodstream. In their immature state, these cells cannot perform their usual functions. The overgrowth of these cells leads to an inadequate number of normal, healthy blood cells, including white blood cells, red blood cells, and platelets. This can result in:

●Neutropenia (low numbers of neutrophils) – Neutrophils are a type of white blood cell that helps to fight infection. People with neutropenia are more likely to get infections.

●Anemia (low numbers of red blood cells) – Red blood cells circulate in the blood vessels and carry oxygen to our tissues. People without enough red cells may be pale and are often tired and short of breath.

●Thrombocytopenia (low numbers of platelets) – Platelets are small cells in the blood that help to prevent and stop bleeding. People with low platelets have bleeding and spontaneous bruising.

More detailed information about AML, written for healthcare providers, is available by subscription. (See 'Professional level information' below.)

CANCER CARE DURING THE COVID-19 PANDEMIC — COVID-19 stands for "coronavirus disease 2019." It is an infection caused by a virus called SARS-CoV-2. The virus first appeared in late 2019 and has since spread throughout the world. Getting vaccinated lowers the risk of severe illness; experts recommend COVID-19 vaccination for anyone with cancer or a history of cancer.

In some cases, if you live in an area with a lot of cases of COVID-19, your doctor might suggest rescheduling or delaying medical appointments. But this decision must be balanced against the importance of getting care to screen for, monitor, and treat cancer. Your doctor can talk to you about whether to make any changes to your appointment schedule. They can also advise you on what to do if you test positive or were exposed to the virus.

GENERAL INFORMATION ABOUT ACUTE MYELOID LEUKEMIA TREATMENT — A number of chemotherapy medications are effective against AML. The goal of treatment is to kill the malignant cells without damaging the residual normal bone marrow cells. 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. These genetic changes are due to mutations that are acquired within bone marrow stem cells and thereby affect all of the malignant daughter cells that are produced. It is not known how these mutations develop. They are generally not thought to be inherited but rather develop by chance. Treatment of AML depends upon your specific subtype of AML. For example, people with a certain type of AML, called "acute promyelocytic leukemia," may be treated with other (non-chemotherapy) medications. Treatment also depends on your age and the presence of any other active medical problems. (See 'Acute myeloid leukemia treatment in older people' below.)

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

INDUCTION OF REMISSION IN ACUTE MYELOID LEUKEMIA — The initial phase of treatment is referred to as remission induction or induction therapy. Induction therapy (with chemotherapy drugs) is given with the goal of decreasing the number of leukemia cells to an undetectable level and thereby restoring the production of normal blood cells.

Chemotherapy refers to the use of medicines to stop or slow the growth and longevity of cancer cells. Chemotherapy targets growing cells, interfering with their ability to divide or multiply. Because most of an adult's normal body cells are not actively growing, they are not as affected as much by chemotherapy as the cancer cells. However, the normal cells in the bone marrow (where the blood cells are produced), hair follicles, and the lining of the gastrointestinal (GI) tract are all growing. Effects of chemotherapy on these and other normal tissues cause side effects during treatment, including hair loss, nausea, anemia (lowered red blood cell count), an increased risk of infection (lowered white blood cell count), and bleeding (lowered platelet count).

Intensive remission induction therapy for AML generally includes a drug called cytarabine, which is usually given continuously for seven days through an intravenous (IV) line plus either daunorubicin or idarubicin, which are given as IV injections on the first three days of treatment; this combination is sometimes called the "7+3" regimen. For leukemia that has developed particular mutations or has certain other characteristics, a third drug may be added to the 7+3 regimen.

These drugs kill AML cells over the first 7 to 14 days, but it takes weeks for the bone marrow to produce enough normal blood cells again. A second course of chemotherapy may be needed if the leukemia did not respond well-enough to the first treatment with 7+3. As a result, intensive remission induction therapy usually requires hospitalization for four or more weeks for supportive care with IV antibiotics and frequent transfusions.

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 when examined under a microscope and that the bone marrow is functioning normally. However, such remissions are usually short-lived unless additional post-remission therapy is given. (See 'Post-remission therapy of acute myeloid leukemia' below.)

For people who decline intensive treatment or who are not suitable for 7+3 because of other medical conditions, there are other, lower-intensity treatments that can control (but do not cure) AML.

Complete remission — The first 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, the bone marrow is functioning normally, and normal numbers of healthy blood cells have returned to the circulation. A bone marrow biopsy and blood testing are done to determine this. Sensitive laboratory methods can sometimes detect leukemia that is not readily observed by a microscope; this is called minimal residual disease (MRD) or measurable residual disease, and its persistence may impact additional treatment plans.

POST-REMISSION THERAPY OF ACUTE MYELOID LEUKEMIA — Post-remission therapy is given with the intention of killing leukemia cells that may remain in the bone marrow or blood, but are undetectable under the microscope.

There are three basic treatment choices for post-remission therapy:

●Additional chemotherapy, sometimes called remission consolidation therapy

●Stem cell transplantation from a healthy donor (allogeneic stem cell transplantation)

●Stem cell transplantation using your own stem cells (autologous stem cell transplantation).

The "best" post-remission treatment depends upon several factors, including how aggressive or resistant to treatment the AML is. People with AML can be classified by risk based on genetic testing of their leukemia cells:

●People with favorable-risk disease are usually advised to continue with chemotherapy. Many of these patients are cured in this way.

●People with unfavorable-risk disease are usually advised to have an allogeneic stem cell transplantation, if possible.

●The best treatment for intermediate-risk disease is not clear; participation in a clinical trial is recommended, when possible. Most AML is intermediate-risk disease. (See 'Clinical trials' below.)

Additional chemotherapy — Chemotherapy given after remission is called remission consolidation or post-remission chemotherapy, and often includes high-dose cytarabine. Consolidation chemotherapy is usually given in the hospital over several days and repeated every four to six weeks. Most patients are able to recuperate at home between courses of chemotherapy, although transfusions are usually required as an outpatient for several weeks until the normal blood counts recover. Consolidation chemotherapy is given for approximately two to six months.

Stem cell transplantation — Stem cell transplantation, also called bone marrow transplantation or hematopoietic cell transplantation (HCT), is a treatment in which you are given very high doses of chemotherapy or total body irradiation (TBI). 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.

Therefore, after this intensive treatment, you must receive a healthy supply of young blood cells (called stem cells) that are reintroduced, or transplanted using transfusion. The transplanted cells then re-establish the blood cell production process in the bone marrow. The new stem cells also generate a new immune system. (See "Patient education: Hematopoietic cell transplantation (bone marrow transplantation) (Beyond the Basics)".)

Stem cell transplantation is not recommended for all patients with AML. Serious, and sometimes even fatal, complications occur more commonly after donor 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 had a relapse following a period of remission, and those who do not achieve complete remission after initial induction therapy.

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

●Allogeneic transplantation is generally preferred over autologous transplantation in people with AML. It uses stem cells from a healthy donor, ideally a sibling with a similar genetic makeup (called a matched related donor). 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 cord blood stem cells collected at birth from 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 kills the leukemia cells present in the blood and bone marrow that might be resistant to lower doses of chemotherapy. Second, when stem cells from another person are transfused, some of the donor stem cells mature into immune cells, and these donor immune cells can cause an immune response that helps destroy any remaining leukemia cells. This is called the "graft-versus-leukemia" or "graft-versus-tumor" effect.

Unfortunately, this response is closely associated with a complication called "graft-versus-host disease" in which the immune response includes an attack on some of the patient's own healthy organs. Symptoms can include severe skin rash, diarrhea, liver damage, and other problems.

●In an autologous transplant, your own normal stem cells are collected while you are in complete remission. Shortly afterwards, high-dose chemotherapy or radiation is given. After your chemotherapy or radiation is complete, the harvested cells are returned by intravenous (IV) infusion.

Because the transplanted stem cells do not come from another person, there is no "graft-versus-host" disease. This helps avoid most of the side effects of treatment. However, autologous transplantation is also somewhat less effective than allogeneic transplantation in fighting the leukemia, because of the lack of a "graft-versus-leukemia" effect. Autologous transplantation is less often recommended for treatment of AML for this reason.

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

●Difficult-to-treat (chemotherapy resistant) 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.

In older people with slowly progressing AML, severe underlying health problems, or genetically high-risk and unfavorable AML, the expected benefit of chemotherapy may not be worth the anticipated discomfort, hospitalization, and potentially toxic side effects. Less intensive chemotherapy regimens are under development for older patients and enrollment on a clinical trial of one of these regimens may be suggested. 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 or bleeding 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 to determining the best course of action for you. Many new drugs or drug combinations are currently being studied for patients with AML. The best treatment for you may include a clinical trial so that you can have access to the latest new drugs. (See 'Clinical trials' below.)

TREATMENT OF RELAPSED OR RESISTANT ACUTE MYELOID LEUKEMIA — A limited number of treatments are effective in the treatment of AML that does not respond to induction therapy or AML that relapses after initial chemotherapy:

●About half of people with first remissions that last at least one year benefit from a second treatment with remission induction therapy. Such treatment might include high-dose cytarabine (HiDAC), daunorubicin (or idarubicin) plus cytarabine, or similar drug combinations. For patients whose relapsed AML has a mutation in the IDH1 gene or the IDH2 gene, treatment with an oral drug called ivosidenib or enasidenib, respectively, is another option. Patients with AML that has a mutation in the FLT3 gene may respond to an oral drug called gilteritinib. Stem cell transplantation should be considered for patients with relapsed AML after 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 likelihood 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, 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 and have completed post-remission therapy, you will need long-term monitoring so that any relapse can be detected quickly and treated. Relapse is most likely to occur within the first two years after completion of induction chemotherapy, and it 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 ever been treated with chemotherapy for another disorder 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.

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/about-cancer/treatment/clinical-trials

●clinicaltrials.gov/

Videos addressing common questions about clinical trials are available from the American Society of Clinical Oncology (www.cancer.net/research-and-advocacy/clinical-trials/welcome-pre-act).

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 on our website (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 — UpToDate offers two types of patient education materials.

The Basics — The Basics patient education pieces answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials.

Patient education: Acute myeloid leukemia (AML) (The Basics)
Patient education: Leukemia in adults (The Basics)
Patient education: Neutropenia and fever in people being treated for cancer (The Basics)

Beyond the Basics — Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are best for patients who want in-depth information and are comfortable with some medical jargon.

Patient education: Hematopoietic cell transplantation (bone marrow transplantation) (Beyond the Basics)

Professional level information — Professional level articles are designed to keep doctors and other health professionals up-to-date on the latest medical findings. These articles are thorough, long, and complex, and they contain multiple references to the research on which they are based. Professional level articles are best for people who are comfortable with a lot of medical terminology and who want to read the same materials their doctors are reading.

Clinical manifestations, pathologic features, and diagnosis of acute myeloid leukemia
Clinical manifestations, pathologic features, and diagnosis of acute promyelocytic leukemia in adults
Acute myeloid leukemia: Cytogenetic abnormalities
Acute myeloid leukemia: Induction therapy in medically fit adults
Initial treatment of acute promyelocytic leukemia in adults
Molecular biology of acute promyelocytic leukemia
Acute myeloid leukemia: Molecular genetics
Acute myeloid leukemia: Overview of complications
Acute myeloid leukemia: Pathogenesis
Acute myeloid leukemia in younger adults: Post-remission therapy
Acute myeloid leukemia: Risk factors and prognosis
Therapy-related myeloid neoplasms: Epidemiology, causes, evaluation, and diagnosis
Acute myeloid leukemia: Management of medically unfit adults
Treatment of relapsed or refractory acute myeloid leukemia
Treatment of relapsed or refractory acute promyelocytic leukemia in adults
Acute myeloid leukemia: Induction therapy in medically fit adults, section on 'Introduction'

The following organizations also provide reliable health information.

●National Library of Medicine (medlineplus.gov/healthtopics.html)

●National Cancer Institute (www.cancer.gov/about-cancer)

●American Cancer Society (www.cancer.org)

●The Leukemia & Lymphoma Society (www.lls.org)

●National Marrow Donor Program (bethematch.org/)

●The American Society of Clinical Oncology (https://www.cancer.net/cancer-types/leukemia-acute-myeloid-aml)

●The American Society of Hematology (www.hematology.org/education/patients)

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