Acute Myeloid Leukemia (AML)

What happens in AML

Bone marrow normally produces red cells (to carry oxygen), white cells (to fight infection) and platelets (to stop bleeding). In AML, genetic changes in an early myeloid cell make it multiply uncontrollably without maturing. These leukemic blasts fill the marrow and spill into the blood. The result is a shortage of normal cells:

• too few red cells: anemia
• too few working white cells: infections (neutropenia)
• too few platelets: bruising and bleeding (thrombocytopenia)

AML is called "acute" because it progresses within weeks to months without treatment, unlike chronic leukemias.

Symptoms

Symptoms usually develop over a few weeks:

• fatigue, weakness and breathlessness on exertion
• pale skin
• fevers and infections that are frequent or slow to clear
• easy bruising and tiny red or purple spots (petechiae)
• bleeding: nosebleeds, bleeding gums, heavy periods
• bone or joint pain
• weight loss, night sweats and loss of appetite
• swollen, overgrown gums or skin lumps (leukemia cutis), especially in monocytic subtypes
• fullness under the left ribs from an enlarged spleen (less common than in chronic leukemias)

Acute promyelocytic leukemia (APL), a subtype, can cause dangerous bleeding and clotting at diagnosis and is a medical emergency.

Causes and risk factors

Most cases have no identifiable cause. Known risk factors include:

• older age
• previous chemotherapy or radiotherapy for another cancer (therapy-related AML)
• myelodysplastic syndrome and other blood disorders that can transform into AML
• smoking
• benzene exposure in industry
• genetic conditions such as Down syndrome, Fanconi anemia and inherited predisposition syndromes
• high-dose radiation exposure

AML is not contagious and is usually not inherited.

Diagnosis

1. Complete blood count and blood film: often show low red cells and platelets, an abnormal white count (high or low), and blasts.
2. Bone marrow aspirate and biopsy: usually from the back of the hip bone under local anesthetic. AML is generally diagnosed when blasts make up 20 percent or more of marrow cells, or at lower levels with certain genetic changes.
3. Flow cytometry: identifies the type of leukemia cells.
4. Cytogenetics and molecular testing: look for chromosome changes and mutations (such as FLT3, NPM1, IDH1/2, TP53). These determine risk and guide targeted treatment.
5. Other tests: clotting tests, kidney and liver function, heart scan before chemotherapy, and sometimes a lumbar puncture.

AML is classified by its genetic features rather than stages. Risk groups are favorable, intermediate or adverse.

Treatment

Treatment begins quickly, often within days of diagnosis, at a specialist center.

For people fit for intensive treatment

• Induction chemotherapy: typically cytarabine plus an anthracycline ("7+3"), with added targeted drugs depending on the genetics, such as a FLT3 inhibitor or gemtuzumab ozogamicin. The aim is remission: no detectable leukemia in the blood and marrow.
• Consolidation: further courses of chemotherapy to destroy remaining leukemia cells.
• Allogeneic stem cell transplant: from a donor, offered in first remission to people with intermediate or adverse risk who are fit enough. It gives the best chance of cure in higher-risk AML.
• Maintenance therapy in some cases.

For older or less fit people

Lower-intensity treatment, most commonly venetoclax combined with azacitidine or decitabine, has improved outcomes for people who cannot tolerate intensive chemotherapy. Targeted drugs (IDH1 or IDH2 inhibitors, FLT3 inhibitors) are options for specific mutations.

Acute promyelocytic leukemia

APL is treated with all-trans retinoic acid (ATRA) and arsenic trioxide, often without conventional chemotherapy, and has cure rates above 90 percent.

Supportive care

• blood and platelet transfusions
• antibiotics, antifungals and prompt treatment of fever
• medicines to prevent tumor lysis syndrome at the start of treatment
• nutrition, mouth care and emotional support

Complications

• life-threatening infections during low blood counts
• bleeding, including in the brain
• tumor lysis syndrome and kidney damage
• leukostasis: very high white cell counts blocking small vessels in the lungs and brain
• side effects of treatment, and graft-versus-host disease after transplant
• relapse

Outlook

Outcomes vary widely. For all adults in the US, about 3 in 10 survive 5 years, according to NCI SEER data. Younger adults with favorable genetic features have much higher cure rates, with roughly 6 to 7 in 10 children cured, while outcomes are poorer in people over 65 or with adverse-risk genetics. New targeted and combination treatments continue to improve results. A clinical trial is worth discussing at diagnosis.

Frequently asked questions

What are the first signs of acute myeloid leukemia?

Early signs include tiredness, pale skin, breathlessness, frequent infections or fevers, easy bruising, tiny red spots on the skin, nosebleeds and bleeding gums. They usually develop over a few weeks. A simple blood count is the first test.

Is AML curable?

Yes, for some people. Intensive chemotherapy, sometimes followed by a stem cell transplant, cures a significant proportion of younger adults, and most children and people with acute promyelocytic leukemia. Cure is less common in older adults, though newer treatments extend life.

How fast does AML progress?

AML progresses quickly, over weeks to a few months, without treatment. That is why treatment usually starts within days of diagnosis. Some cases develop from a slower condition such as myelodysplastic syndrome.

What is the difference between AML and ALL?

Both are acute leukemias. AML arises from myeloid cells, which normally become granulocytes, red cells and platelets, and is commoner in older adults. ALL arises from lymphoid cells and is the most common childhood cancer. Their treatments differ.

What causes acute myeloid leukemia?

Most cases arise from random genetic changes in blood-forming cells, with no clear cause. Risk factors include older age, prior chemotherapy or radiation, myelodysplastic syndrome, smoking, benzene exposure and some genetic conditions such as Down syndrome.