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

The leukemia cells in APL (called blasts) aren't able to mature into normal white blood cells, and they can grow and divide very quickly. These cells contain proteins that when released into the bloodstream can cause out-of-control blood clotting. This can lead to problems not only with blood clots, but also with severe bleeding. In the past, when standard chemo drugs were used alone to kill APL cells, these proteins were released into the bloodstream, and some people died from clotting or bleeding complications.

Researchers have found that the leukemia cells in APL have a specific gene change that makes them sensitive to certain drugs that aren’t like standard chemo drugs. These drugs help the blasts mature into normal white blood 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. But these drugs can also have side effects of their own.

Two of these drugs can be used to treat APL:

• All-trans-retinoic acid (ATRA, tretinoin, or Vesanoid)
• Arsenic trioxide (ATO, Trisenox)

For more on how these drugs are used for APL, see Treatment of Acute Promyelocytic Leukemia (APL).

All trans-retinoic acid (ATRA)

ATRA is a medicine related to vitamin A. It is typically part of the initial (induction) treatment of APL, either along with chemo, or along with arsenic trioxide (see below). It is also often used for some time after as part of the consolidation phase of treatment to help keep the leukemia from coming back. For this phase of treatment, it may be used with chemo or with arsenic trioxide (or possibly with both). For longer-term maintenance, ATRA might be used by itself or 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 liver blood test results become abnormal. These side effects often go away when the drug is stopped.

Arsenic trioxide (ATO)

Arsenic trioxide (ATO) can act in a way similar to ATRA in patients with APL. It can be given with ATRA in the induction and consolidation phases of treatment, but it is also helpful in treating people whose APL comes back after treatment with ATRA plus chemo. In these people, ATO might be given along with ATRA and/or the targeted drug gemtuzumab ozogamicin (Mylotarg).

Side effects of ATO 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 couple of weeks of treatment, and in people with a high white blood cell count.

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. While differentiation syndrome can be serious, it can often be treated by stopping the drugs for a while and giving a steroid such as dexamethasone.