Non-Chemo Drugs for Acute Promyelocytic Leukemia

Chemotherapy is the main treatment for most types of acute myeloid leukemia (AML). But acute promyelocytic leukemia (APL or AML M3) is different from other types of AML in some important ways.

The leukemia cells (or blasts) in APL contain proteins that when released into the bloodstream can cause the blood to clot in an out-of -control way. This can lead to problems not only with blood clots, but also with severe bleeding. In the past, when regular chemotherapy (chemo) drugs were used alone to kill these cells, these proteins were released into the bloodstream. Patients sometimes died from complications from the out-of-control clotting or bleeding.

Experts realized that the leukemia cells in APL have a specific gene change that makes them sensitive to certain drugs that aren’t like regular chemo drugs. These drugs signal the blasts to transform into mature myeloid cells. This process is known as differentiation, and these drugs are called differentiation agents. Since the blasts don’t die, they don’t release the harmful proteins into the blood, which helps keep the clotting process from getting out of control.

There are 2 drugs that are used for this in APL: all-trans-retinoic acid (ATRA, tretinoin, or Vesanoid®) and arsenic trioxide (ATO, Trisenox®).


ATRA is a form of vitamin A that is often part of the initial (induction) treatment of APL. It is often given along with chemo. It can also be given with arsenic trioxide for the initial treatment of APL, in which case no regular chemo drugs are given. If ATRA is part of the initial treatment for APL, it is often used for some time after to help keep the leukemia from coming back. For the consolidation phase of treatment, it may be used with chemo, with arsenic trioxide, or with both chemo and arsenic trioxide. For longer-term maintenance, ATRA might be used by itself or along with chemo.

ATRA can have side effects similar to those seen if you take too much vitamin A. Symptoms can include headache, fever, dry skin and mouth, skin rash, swollen feet, sores in the mouth or throat, itching, and irritated eyes. It can also cause blood lipid levels (like cholesterol and triglycerides) to go up. Often blood liver tests become abnormal. These side effects often go away when the drug is stopped.

Arsenic trioxide

Arsenic trioxide (ATO) is a form of arsenic, which can be a poison if given in high doses. But doctors found that it can act in a way similar to ATRA in patients with APL. It can be given with ATRA as the first treatment, but it is also helpful in treating patients whose APL comes back after treatment with ATRA plus chemo. In these patients, ATO is given without chemo.

Most side effects of ATO are mild and can include fatigue (tiredness), nausea, vomiting, diarrhea, abdominal (belly) pain, and nerve damage (called neuropathy) leading to numbness and tingling in the hands and feet. ATO can also cause problems with heart rhythm, which can be serious. Your doctor may check your heart rhythm with an EKG often (even daily) while you are getting this drug.

Differentiation syndrome

The most important side effect of either of these drugs is known as differentiation syndrome (previously called retinoic acid syndrome). This occurs when the leukemia cells release certain chemicals into the blood. It is most often seen during the first cycle of treatment.

Symptoms can include fever, breathing problems due to fluid buildup in the lungs and around the heart, low blood pressure, kidney damage, and severe fluid buildup elsewhere in the body. It can often be treated by stopping the drugs for a while and giving a steroid such as dexamethasone.

The American Cancer Society medical and editorial content team
Our team is made up of doctors and master's-prepared nurses with deep knowledge of cancer care as well as journalists, editors, and translators with extensive experience in medical writing.

Last Medical Review: December 9, 2014 Last Revised: February 22, 2016

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