• Acute promyelocytic leukemia (APL) is one of several subtypes of acute myeloid leukemia, a blood cancer that originates in a person's bone marrow.
• APL is caused by a genetic mutation, but it is not a hereditary condition.
• APL is a potentially life-threatening disease; however, it is the most curable form of adult leukemia.

What Is Acute Promyelocytic Leukemia?

Acute promyelocytic leukemia (APL) is an aggressive form of acute myeloid leukemia (AML), a cancer of the bone marrow. Acute promyelocytic leukemia gets its name from promyelocytes, immature white blood cells. APL causes an accumulation of promyelocytes in the bone marrow, which crowds out other normal cells in the blood. APL is sometimes also referred to as AML M3.

The bone marrow is where blood cell production happens. In healthy bone marrow, immature cells called myeloblasts become myelocytes. Myelocytes mature into white blood cells, or granulocytes. In APL, promyelocytes — cells between the myeloblast and myelocyte stage — stop maturing but continue to crowd the bone marrow.

Unlike most cancers, there is no standard staging system for acute myeloid leukemia or acute promyelocytic leukemia. Instead, doctors use the terms “untreated,” “in remission,” or “recurrent” to describe the disease progression.

Learn more about acute myeloid leukemia and other types of leukemia.

Who Is Affected by Acute Promyelocytic Leukemia?

Between 600 and 800 cases of acute promyelocytic leukemia are newly diagnosed each year in the United States. APL occurs in approximately 1 in 250,000 people in the U.S. APL is most prevalent in people of Hispanic descent. People of Asian and Pacific Islander descent have the lowest rates of APL diagnoses.

APL in Adults

Acute promyelocytic leukemia can occur at any age, but it is most often diagnosed in adults around age 40. APL makes up around 10 percent of acute myeloid leukemia diagnoses in adults.

APL in Children

Childhood APL accounts for between 4 percent and 8 percent of all pediatric acute myeloid leukemia diagnoses. Childhood APL is usually diagnosed between the ages of 8 and 10. In children younger than 3, APL is very rare. Pediatric APL accounts for about 1 percent of all leukemias seen in children.

Risk Factors

There several factors that may put a person at increased risk of developing acute myeloid leukemia in general, which includes APL.

• Age — The risk of developing acute myeloid leukemia rises as you get older.
• Certain blood disorders — For example, myelodysplastic syndrome is an AML risk factor.
• Chemotherapy drugs — People who undergo chemotherapy for cancer, specifically alkylating agents and topoisomerase II inhibitors, may be at risk of developing AML later in life.
• Radiation therapy — This includes exposure in high doses, such as a nuclear disaster, as well radiation therapy for cancer treatment.
• Chemical exposure — For example, long-term exposure to benzene can increase risk.
• Family history of AML — This increases risk, even though AML is not a hereditary disease.
• Sex — Males are more likely to develop AML than females.
• Genetic and chromosomal disorders — Some conditions, such as Down syndrome and Bloom syndrome, can increase AML risk.
• Smoking — This is the one lifestyle factor in a person’s control that is linked to a risk of developing AML.

Most people with one — or even several — of these risk factors won’t develop leukemia. Some people diagnosed with AML or APL do not have any of these risk factors. Doctors recommend people at higher risk of developing AML get regular medical checkups.

What Causes Acute Promyelocytic Leukemia?

Acute promyelocytic leukemia is caused by a genetic mutation, however, it is not an inherited condition. APL is caused by a mutation that involves two genes: the promyelocytic leukemia (PML) gene on chromosome 15 and the retinoic acid receptor alpha (RARA) gene on chromosome 17. This mutation is called PML-RARA gene fusion and is seen in as many as 98 percent of APL cases.

Symptoms of Acute Promyelocytic Leukemia

Symptoms of APL vary from person to person. Not everyone will experience all of the symptoms listed. APL symptoms are due to insufficient healthy blood cells and a buildup of cancer cells, or leukemic cells, in the bone marrow. APL can sometimes involve the central nervous system, in which case neurological symptoms may occur.

Early on, people with APL may feel a general malaise — fatigue, mild fever, and low appetite and weight loss.

Signs and symptoms of APL may include:

• Anemia
• Blood in urine (hematuria)
• Bruises
• Enlarged spleen and liver
• Frequent infections
• Headaches
• Joint or bone pain
• Nosebleeds
• Pale skin
• Small red dots under the skin (petechiae)
• Swelling or bleeding gums
• Very heavy menstrual flow
• Visual changes

Because of a lack of mature white blood cells, people with APL can be immunosuppressed and more susceptible to infections. A low platelet count also leads to issues with proper blood clotting, which can put someone at risk for internal bleeding in the brain or lungs.

The signs and symptoms of APL may mimic symptoms of other common illnesses, like the flu. It is important to discuss symptoms with your doctor, as prompt diagnosis of APL is key to successful treatment.

How Is Acute Promyelocytic Leukemia Diagnosed?

APL is grouped into two risk categories.The risk categories are based on a person’s white blood cell (WBC) count.

• Low risk — WBC count of less than 10,000 white blood cells per microliter of blood
• High risk — WBC count of more than 10,000 white blood cells per microliter of blood

Diagnosing APL is commonly done through a combination of laboratory tests, a detailed medical history, and a physical exam.

Blood and Bone Marrow Tests

Doctors often use blood and bone marrow tests, including bone marrow aspiration and biopsy, to see if there are abnormal APL cells present. A change in the quantity and appearance of blood cells is an important part of making an accurate, timely diagnosis.

Coagulation Tests

The body’s ability to form blood clots is known as coagulation. To determine whether or not a person is at high risk for bleeding, doctors may order coagulation status tests and imaging scans to check the blood’s ability to clot.

Genetic Tests

To diagnose APL and rule out the possibility of any other subtypes of AML, doctors have to confirm the presence of the PML-RARA gene mutation. Cytogenetic tests used to identify this gene mutation include karyotyping and fluorescence in situ hybridization (FISH). Doctors may also order a test called polymerase chain reaction. A PCR test examines blood or bone marrow cells to identify changes in their genetic structure.

Prompt diagnosis of APL is vital. The Leukemia & Lymphoma Society recommends starting treatment for APL as soon as possible, as potentially life-threatening complications can occur if it is left untreated.

How Is Acute Promyelocytic Leukemia Treated?

Low-risk APL is usually treated with less intensive regimens than high-risk APL. Pediatric APL is generally treated with the same therapies as adult APL cases. A person’s age, the state of their health, and the risk classification of their APL determine what treatment regimen a doctor will prescribe. Treating APL is different from treatment approaches for other types of acute myeloid leukemia. APL treatment is commonly undergone in three phases.

Phase 1: Induction

Induction therapy begins as soon as possible after diagnosis. The goal of induction therapy is to minimize APL-related symptoms and achieve complete hematologic response (CHR). CHR is achieved by killing as many APL cells as possible and normalizing blood-cell counts.

Phase 2: Consolidation

Consolidation therapy begins after the induction phase. The primary goal of this phase of treatment is to achieve full remission by building on successful CHR. Ideally, this phase will ensure no residual disease remains.

Phase 3: Maintenance

Maintenance therapy aims to keep a person in remission, or avoid APL recurrence, for as long as possible. This phase includes regular post-remission follow-up and monitoring with your doctor. Remission may be sustained using lower doses of medication over a long period of time, depending on a person’s risk classification. This phase of treatment usually lasts between one and two years.

Treatment options for APL may include one or a combination of the following drugs:

• All-trans retinoic acid (ATRA)
• Arsenic trioxide
• Anthracyclines
• Antimetabolites

In rare cases, hematopoietic stem cell transplants (either allogeneic or autologous) may be used if other treatments don’t achieve remission.

Depending on several factors, some people with APL may enroll in clinical trials. Ask your health care provider if a clinical trial is right for you.

Potential Side Effects and Complications of APL Treatment

Treatments for APL can cause unpleasant side effects. Side effects depend on how healthy the person is when they begin treatment, the type and dosage of drug, and the duration of treatment. Fortunately, most of the side effects are temporary and usually go away after treatment is complete.

Bleeding

Platelets are the cells in the blood that enable it to clot. APL can cause low platelet counts and insufficient clotting factors in the blood. This can lead to excessive bleeding. People with high-risk APL are at a greater risk for increased bleeding. Minor bleeding — which may look like frequent nosebleeds or easy bruising — may occur earlier in the APL disease course. More serious bleeding, such as in the brain or lungs, can sometimes follow these minor symptoms and can be fatal. Before starting treatment, people with APL should be tested for blood clotting ability and supported with platelet or plasma transfusions if necessary.

Infection

Low white blood cell counts due to APL can impair the immune system. When a person’s immune system is compromised, they’re more susceptible to infection — which is usually of greater concern during treatment.

Differentiation Syndrome

Differentiation syndrome is a serious potential complication of APL treatment. Differentiation syndrome usually occurs within 21 days after treatment begins. Symptoms of differentiation syndrome include fever, rash, low blood pressure, and fluid buildup. Accumulation of fluid around the heart and lungs can be particularly dangerous. People undergoing treatment for APL must be closely monitored for signs of differentiation syndrome.

Prognosis for Acute Promyelocytic Leukemia

Thanks to diagnostic advances and improved treatments, APL is considered the most curable form of adult leukemia. Treatment for adults with APL often offers cure rates of 90 percent, with a two-year overall survival rate over 90 percent. Following combined treatment of ATRA and anthracycline chemotherapy, people with high-risk APL face between a 15 percent and 25 percent chance of relapse.

At least 85 percent to 90 percent of children who undergo treatment for APL are expected to be cured. That said, an APL diagnosis in children is considered a medical emergency and immediate treatment is advised.

Do you have acute promyelocytic leukemia? Have you been through treatment? What advice do you have for others with APL? Comment below or start a conversation on MyLeukemiaTeam and connect with people who understand your experience.