Acute Promyelocytic Leukemia

What is acute promyelocytic leukemia (APL)?

Acute promyelocytic leukemia (APL) is a rare blood cancer. It’s a form of acute myeloid leukemia that happens when a genetic mutation (change) creates abnormal white blood cells that multiply uncontrollably in your bone marrow. Healthcare providers may call this condition APL leukemia or M3-leukemia.

APL is a serious condition with life-threatening symptoms, including excessive bleeding, which come on suddenly and quickly get worse. Thanks to treatment that’s an innovative combination of chemotherapy and non-chemotherapy drugs, healthcare providers can treat and often cure acute promyelocytic leukemia.

How common is this condition?

APL is rare, affecting 30,000 people in the U.S. each year. Most people are in their 30s when they receive an APL diagnosis.

What are the symptoms of acute promyelocytic leukemia?

Acute promyelocytic leukemia (APL) symptoms develop when your bone marrow can’t make normal numbers of red blood cells, white blood cells and platelets. If you have low blood cell levels (pancytopenia), you may develop serious symptoms, including anemia, bleeding issues (hemorrhage) and infections.

Other APL symptoms are:

• Fatigue from anemia, or low red blood cells.
• Frequent infections because you have low levels of infection-fighting white blood cells.
• Unintentional weight loss because your metabolism speeds up and you burn energy from food.

Bleeding symptoms

In acute promyelocytic leukemia, you don’t have enough platelets or blood clotting factors. Platelets slow or stop bleeding. Blood clotting factors help make clots in your blood. APL bleeding symptoms include:

• Bleeding from any site, including bleeding gums, nosebleeds or heavy menstrual bleeding.
• Bruising from blood pooling under your skin.
• Difficulty moving your arms and legs, headaches or vision issues from bleeding into your brain (intracranial hemorrhage).
• Poop that looks black or has red streaks of blood. This happens if you have bleeding in your gut (gastrointestinal bleeding).

What causes acute promyelocytic leukemia?

This condition happens when two genes that drive blood cell development fuse to create the abnormal gene PML-RARa. You don’t inherit this genetic mutation (change). It happens randomly during your lifetime. Experts don’t know what triggers the change.

The mutation keeps white blood cells from developing as they should. The immature white blood cells (promyelocytes) multiply uncontrollably, crowding out healthy blood cells and platelets.

What are complications of APL?

APL can be life-threatening, causing severe bleeding that quickly gets worse. Contact a healthcare provider or go to the emergency department if you have bleeding that you can’t control, like bleeding from a cut or injury or there’s lots of blood in the toilet after you poop or pee or bleeding gums.

How is acute promyelocytic leukemia diagnosed?

Healthcare providers typically order the following tests to diagnose this condition:

• Complete blood count (CBC): APL creates abnormal white blood cells. CBC tests show the number of blood cells and platelets in a blood sample.
• Peripheral blood smear: Providers may see high levels of granules or Auer rods inside promyelocytes, a specific type of white blood cell.
• Bone marrow biopsy: Providers order these to get samples of your bone marrow cells for analysis.
• Flow cytometry: In this test, pathologists examine the surface of abnormal cells, checking for specific protein patterns that confirm APL.
• Polymerase chain reaction (PCR) test: This test checks for the abnormal gene that causes APL.
• Cytogenetics: Pathologists will examine abnormal cells for specific changes in chromosomes. Finding those changes is how providers confirm an APL diagnosis.

Healthcare providers use white blood cell counts to classify cases as being low- or high-risk APL. People with high-risk acute promyelocytic leukemia are more likely to experience relapse (recurrent cancer).

How is acute promyelocytic leukemia treated?

APL treatment is a combination of differentiation agents, chemotherapy and targeted therapy. This treatment combination, developed in the 1980s, transformed the condition from a fatal illness to a curable one.

Differentiation agents are non-chemotherapy treatments that help abnormal white blood cells mature (differentiate) into normal white blood cells. The non-chemotherapy treatment described below has increased the remission and cure rate to more than 95%.

Differentiation agents for APL are:

• All-trans-retinoic acid (ATRA), or tretinoin (Vesanoid^®) — a form of vitamin A.
• Arsenic trioxide (ATO), a form of arsenic.

If your healthcare provider suspects you have APL, they’ll likely prescribe ATRA right away, even before tests confirm you have APL. Prompt treatment reduces the risk of life-threatening bleeding.

APL treatment phases

Treatment includes three phases: induction, consolidation and maintenance. Treatments vary, depending on risk:

• Induction: This phase focuses on eliminating enough leukemia cells to put APL into remission. Remission means you don’t have symptoms and tests don’t find signs of leukemia. Induction treatment uses a combination of a non-chemotherapy drug, chemotherapy and targeted therapy. You’ll need to stay in the hospital during induction, which usually lasts four to six weeks.
• Consolidation: Your oncologist may call this post-remission therapy. Consolidation treatment works to keep acute promyelocytic leukemia in remission and eliminate any remaining leukemia cells. This treatment uses the same drugs as induction treatment. You may receive treatment for eight months, with treatment sessions every two months. You may have treatment for four weeks and then a four-week treatment break. Treatment may be taking pills or receiving medication through an intravenous (IV) line.
• Maintenance: This is ongoing treatment in lower doses than induction and consolidation. Typically, people receive maintenance therapy for a year.

Your oncologist may combine treatment with supportive therapy like blood transfusions.

Treatment complications

The most common and serious complication is differentiation syndrome. This is a group of severe reactions to APL drugs. The reactions typically develop during the first three weeks of induction or initial treatment. Symptoms may be mild or severe and include:

• Cough.
• Excess fluid buildup around your heart and lungs (pleural effusion).
• Kidney failure (renal failure).
• Low blood pressure (hypotension).
• Low level of oxygen in your blood (hypoxemia).
• Shortness of breath (dyspnea).
• Swelling (inflammation) of your arms, legs and neck.
• Unexplained fever.
• Unexplained weight gain.

If you experience differentiation syndrome, your provider might stop treatment. They may use other drugs like hydroxyurea to bring down your white blood cell levels.

What can I expect if I have acute promyelocytic leukemia?

In general, the prognosis is good. While everyone’s situation is different, studies show between 90% and 95% of APL cases go into remission. APL can come back (recur) after treatment. Between 5% to 10% of people experience relapse, usually within the first three years after treatment, and need more or different treatment.

Survival rates

Acute promyelocytic leukemia is a rare disease, so what we know about survival rates comes from clinical trials involving people with low-risk and high-risk APL.

One analysis of clinical trials involving low-risk APL cases found that 99% of people were alive four years after treatment. Another analysis of research involving high-risk APL cases shows that 86% of people were alive after five years.

How do I take care of myself?

Acute promyelocytic leukemia (APL) can come back (recur), so it’s important that you make it to your follow-up appointments.

You’ll probably have a check-up every month to two months for the first year after your treatment. After the first year, you’ll probably see your provider every three to four months for the next two years. Follow-up appointments may include tests like CBCs, PCRs and bone marrow biopsy.

When should I go to the emergency room?

APL can come back after treatment, causing symptoms that can get worse very quickly. If you’re in remission from acute promyelocytic leukemia, go to the emergency room right away if you have:

• Bleeding that you can’t control.
• Sudden pain and swelling in your legs or lower belly.