Acute promyelocytic leukemia (APL)

Acute promyelocytic leukemia (APL) is a unique subtype of acute myeloid leukemia (AML). APL cells have a very specific abnormality that involves chromosomes 15 and 17, leading to the formation of an abnormal fusion gene called PML/RARα. This mutated gene causes many of the features of the disease. APL accounts for about 10 percent to 15 percent of all adult AML cases diagnosed each year.  

Promyelocytes are immature white blood cells. In APL, these cells are overproduced and accumulate in the bone marrow. Signs, symptoms, and complications of APL result from the overproduction of these immature white blood cells and the underproduction of healthy blood cells.

Treatment for people with APL differs from treatment for those with other AML subtypes. Because of advances in diagnosis and treatment of this disease, APL is now considered the most curable form of adult leukemia. 

Treatment planning

Treatment decisions are based on a person's age, general health, and APL risk classification. APL is classified into two categories of risk, based on your white blood cell count at diagnosis: 

• Low risk: a white blood cells per microliter of blood (10,000/microliter) or less
• High risk: a white blood cell count of more than 10x10⁹/L at diagnosis

Typically, people with low-risk disease are treated with less intensive regimens than those with high-risk disease. Pediatric patients are often treated with the same or very similar regimens as those used for adults. 

APL treatments and phases

The following treatment may be used for APL.

Induction

Induction therapy starts immediately after diagnosis with the goals to kill as many APL cells as possible, bring blood cell counts to normal levels, and decrease APL-related symptoms.  

Standard treatment for APL is the nonchemotherapy drug all-trans retinoic acid (ATRA, Tretinoin, Vesanoid®). This drug is given orally. It is a differentiating agent that helps the abnormal promyelocytes mature into healthy white blood cells. ATRA causes a marked decrease in the number of leukemia cells in the bone marrow, and a remission frequently occurs.

For people with low-risk APL (those with a white blood cell count of 10X10⁹/L or less at diagnosis), the preferred induction treatment option is ATRA with arsenic trioxide (ATO, Trisenox®). ATO is given by slow intravenous injection.  

For people with high-risk disease (those with a white blood cell count of more than 10x10⁹/L at diagnosis), ATRA and ATO may be combined with idarubicin or gemtuzumab ozogamicin. Other recommended regimens may include ATRA and ATO with daunorubicin or cytarabine. 

Consolidation

Even if you achieve remission after induction, more treatment is needed to destroy any residual leukemia cells in the body. Typically, consolidation uses the same drugs as during induction. Consolidation often uses the same drugs as during induction. 

Maintenance

The third phase of treatment is called maintenance. The main objective of maintenance is to deliver lower doses of drugs to prevent relapse. Maintenance for APL often lasts for a year. Not everyone with APL will receive maintenance. Your doctor may recommend maintenance depending on your risk of relapse.

Relapsed or refractory disease

Despite high remission rates, treatment resistance and relapse can occur. Treatment options for refractory or relapsed AML may include:  

• Clinical trial
• Re-treatment with ATRA and ATO
• Salvage therapy followed by a stem cell transplant either autologous or allogeneic  

Side effects and supportive care  

APL treatment can cause unwanted and unpleasant side effects. Side effects may be caused by the drug type and dose used, length of treatment, and a person's overall health. Side effect management is important. If you have any concerns about side effects, talk to your doctor to get help. Most side effects are temporary and resolve when treatment is completed. However, people with APL may need specific kinds of supportive care.  

Learn more about treatment side effects and how to manage them.