Acute myeloid leukemia (AML) is a type of blood cancer that makes up about 80% of leukemias in adults. Secondary AML (sAML) is when AML evolves from a pre-existing blood condition.

Leukemia is a group of cancers that form in tissues that create blood cells. It’s classified based on the type of cells it develops in and how quickly it’s expected to spread. “Acute” means that AML tends to progress rapidly and “myeloid” means it develops in myeloid cells that become red blood cells, platelets, and some white blood cells.

Secondary AML tends to have a poorer outlook than primary AML, which isn’t associated with a pre-existing condition.

Keep reading to learn more about sAML including what causes it, how it’s diagnosed, and how it’s treated.

The term sAML is now used to refer to AML or myelodysplastic syndrome (MDS) that develops from a pre-existing blood condition. In the past, it was also used to refer to AML that developed after chemotherapy or radiation therapy, but this is now referred to as therapy-related AML (tAML).

Myelodysplastic syndrome (MDS) is a group of cancers in which blood cells in your bone marrow don’t become mature cells. About 1 in 3 cases of MDS progress to AML. Previously, it was called pre-leukemia or smoldering leukemia. It’s now considered a form of cancer.

When AML doesn’t occur after cancer therapy or in the presence of a blood condition, it’s known as primary or de novo (Latin for “of new”) AML. sAML occurs most often in adults over 65 years.

Studies estimate that sAML may make up 10% to 30% of cases of AML or MDS.

In a 2017 study, researchers defined sAML based on if a person had a prior diagnosis of myelodysplastic syndrome, myeloproliferative neoplasm, or aplastic anemia.

  • Myeloproliferative neoplasm is a group of rare blood cancers where bone marrow makes too many blood cells.
  • Aplastic anemia is a disease that leads to the insufficient production of blood cells in your bone marrow.

Symptoms of secondary AML tend to be similar to primary AML, but white blood cell count tends to be low in AML associated with MDS compared with high in primary AML.

General symptoms may include:

Specific symptoms can develop from a low blood cell count. They can include:

Low red blood cell symptomsLow white blood cell symptomsLow platelet symptoms
fatiguefrequent infectionsexcessive bleeding
weaknesslingering infectionsfrequent bruising
shortness of breathfeverfrequent or severe nosebleeds
palenessincreased menstrual bleeding
headachesbleeding gums
feeling cold

AML is thought to develop due to certain genetic mutations in your blood-forming cells.

Stem cells that become blood cells divide about once every 40 weeks and develop about 11 mutations each time they divide. If these mutations occur in a gene linked to leukemia, it can lead to a condition called clonal hematopoiesis.

Clonal hematopoiesis is when a blood stem cell with certain mutations produces cells with the same genetic mutation. The presence of clonal hematopoiesis seems to increase the risk of developing blood cancer by 0.5% to 1% per year.

Some gene mutations are highly specific for sAML. These mutations include: SRSF2, SF3B1, and U2AF1.

Risk factors for AML

Risk factors for AML are known to include:

  • increased age
  • being male
  • smoking
  • long-term exposure to some chemicals, such as benzene
  • exposure to radiation or chemotherapy drugs (for tAML)
  • having certain blood disorders (for sAML)
  • certain genetic syndromes, such as Down syndrome
  • family history

Diagnosing sAML requires a biopsy of your bone marrow. If your doctor knows that you have a history of a previous blood disorder, radiation therapy, or chemotherapy, they may be able to make an sAML or tAML diagnosis if they see signs of AML in your biopsy sample.

The presence of genetic abnormalities associated with a blood condition in your biopsy sample can also be used to make a diagnosis.

A blood test can provide supportive evidence, such as a low blood cell count.

Secondary AML is generally harder to treat than primary AML, and researchers are continuing to examine new treatment options.


The drug Vyxeos (daunorubicin and cytarabine liposome for injection) was FDA approved for sAML in 2017. It’s typically given in 90-minute transfusions through an IV three times per day every second day.

In a 2018 phase 3 clinical trial, researchers found that Vyxeos led to complete remission in 47.7% of people versus 33.3% in people who received the drugs daunorubicin and cytarabine separately.

Vyxeos can cause severely low blood counts. It can take platelet levels 1 to 2 weeks longer to recover than with traditional chemotherapy.

Doctors sometimes recommend a class of drugs called hypomethylating agents for people who may benefit from less intensive therapy.

Stem cell transplants

Chemotherapy is often combined with a stem cell transplant. After receiving a very high dose of chemotherapy, you’ll receive a replacement of your bone marrow to replace the blood-forming cells that were killed.

A stem cell transplant can potentially improve your chances of survival by increasing the amount of chemotherapy you can handle.

Stem cell transplants are generally only an option for people under the age of 60 to 65. But some researchers suggest that some people over 70 years who are in good health should be considered.

Targeted therapy

Mutations in the genes IDH1 and IDH2 are seen in about 5% and 20% of people with sAML, respectively. Targeted drugs called ivosidenib and enasidenib may help treat people with these mutations, but these drugs take several months to reach their maximum effect.

The outlook for people with sAML is generally worse than for people with primary AML. However, people with sAML tend to be older and frailer, which may contribute to a poorer outlook.

Survival is estimated to be 6 to 12 months even with intensive chemotherapy. AML developing from MDS seems to have a better outlook than AML developing from a non-MDS blood condition.

Risk factors associated with a worse outlook include:

  • certain genetic abnormalities or mutations
  • increasing age
  • inability to undergo daily activities (performance status)
  • multidrug resistance
  • presence of coexisting health conditions

Secondary AML (sAML) is when AML develops from a previous blood condition. It generally has a worse outlook than primary AML.

Researchers are continuing to examine new treatments for sAML. If you or your loved one receives a diagnosis of sAML, be sure to discuss treatment options with your doctor. They can give you an idea of what might work best for you and what to expect from treatment.

Your doctor can also recommend clinical trials you may be eligible for, and let you know alternative options if first-line therapy doesn’t work.