ATRA and ATO

Say it: AY-truh and A-T-O

Tretinoin and arsenic trioxide

ATRA and ATO is a mostly chemotherapy free treatment that cures most people with acute promyelocytic leukemia (APL).

Also called: ATRA ATO, ATRA plus arsenic, tretinoin and arsenic trioxide, ATRA/ATO, APL0406 regimen, chemo free APL treatment

What it is

APL is a special type of leukemia caused by a gene swap that traps blood cells in an immature stage. Tretinoin (a form of vitamin A) and arsenic trioxide both break this block so the leukemia cells grow up and die off. Used together, they cure the large majority of people with APL. Treatment has two phases: induction to reach remission, then consolidation to keep it away.

Often used for

• Acute promyelocytic leukemia (APL), low or intermediate risk
• High risk APL, often with a short course of chemotherapy added

High risk APL

If the white blood cell count is high at diagnosis, a short course of chemotherapy (such as idarubicin) or gemtuzumab ozogamicin is usually added during induction.

Oral arsenic

In some countries, arsenic is given as a pill instead of through a vein. It is not yet standard everywhere.

The medicines in this plan

Tretinoin (ATRA)

A vitamin A based capsule taken twice a day with food. It starts right away, often even before the diagnosis is fully confirmed.

Arsenic trioxide (ATO)

A medicine given through a vein over about 2 hours, daily at first and later 5 days a week in blocks.

How you get it

Induction starts in the hospital because the first weeks carry the highest risk of bleeding and other problems. Arsenic is given daily and tretinoin is taken twice daily until remission, often about 4 to 8 weeks. Consolidation is given in the clinic: arsenic 5 days a week for 4 weeks on and 4 weeks off, and tretinoin 2 weeks on and 2 weeks off, for about 7 months. Your schedule may be different.

A typical cycle

Diagnosis and first days

Hospital admission. Tretinoin starts at once. Blood, platelet and plasma transfusions correct clotting problems.

Induction (about 4 to 8 weeks)

Daily IV arsenic and twice daily tretinoin. Daily blood tests and frequent heart tracings (ECGs).

End of induction

A bone marrow test checks for remission. Most people can go home before this point once stable.

Consolidation (about 7 months)

Clinic visits for arsenic 5 days a week in 4 week blocks, with tretinoin 2 weeks on and 2 weeks off.

After treatment

Blood or bone marrow tests for the APL gene change confirm the leukemia is gone.

Common side effects and what helps

• Headache from tretinoin, sometimes severe. Tell your team, since this can be a sign of pressure around the brain.
• Dry skin, lips and eyes. Use lip balm, moisturizer and eye drops.
• Tiredness. Rest and short walks help.
• Nausea and loss of appetite. Eat small meals often.
• Fluid buildup and weight gain. Weigh yourself each day if asked.
• Changes in heart rhythm on the ECG from arsenic. Potassium and magnesium are kept in a safe range.
• Tingling or numbness in hands and feet from arsenic. Report it at visits.
• Rising white blood cell count early in treatment. This is expected and is watched closely.
• Bone or joint aches. Ask your team which pain reliever is safe.

Call your care team right away if you have

• Shortness of breath, a new cough, chest pain or fast weight gain (signs of differentiation syndrome)
• A fever of 100.4 degrees Fahrenheit (38 degrees Celsius) or higher, or chills
• Bleeding that will not stop, a bad nosebleed, blood in urine or stool, or many new bruises
• A sudden, severe headache, vision changes, confusion or weakness on one side
• Fainting, a racing or fluttering heartbeat, or feeling dizzy
• Swelling in the legs or belly

Good to know

• APL is a medical emergency at diagnosis because of bleeding and clotting problems. Treatment starts right away.
• Differentiation syndrome can happen in the first weeks: fever, trouble breathing, fluid buildup and kidney problems. It is treated quickly with steroids.
• Arsenic can prolong the QT interval (a heart rhythm measure). You will have ECGs often, and potassium and magnesium are checked and replaced.
• Avoid other medicines that affect heart rhythm unless your team approves them.
• Tretinoin can cause serious birth defects. Pregnancy must be avoided during treatment and for a period after.
• Despite the name, the arsenic dose is carefully controlled and is a proven, approved leukemia medicine.

At home

• Take tretinoin with food, twice a day, at the same times.
• Keep a list of all your medicines and show it to every doctor and pharmacist.
• Weigh yourself daily during induction if your team asks, and report quick gains.
• Use moisturizer, lip balm and eye drops for dryness.
• Use a soft toothbrush and avoid activities that could cause injury while platelets are low.

Questions to ask

• Is my APL low risk or high risk?
• How long will I be in the hospital?
• What are the signs of differentiation syndrome?
• Which medicines should I avoid because of my heart rhythm?
• How will we know the leukemia is gone?
• How long will consolidation last?

Leukemia

Last updated: 2026-10-27. Medically reviewed by Veli Bakalov, MD, medical oncologist (October 2026). General education from Step by Step, the patient portal of HemeOncBuddy.