ATRA is still the basis of treatment approaches; ATRA is given orally with anthracycline at low doses during induction treatment. This is then followed by more cycles of consolidation-phase therapy in parallel with chemotherapy. It is sometimes given again together with anthracycline and Ara-C. In many cases, ATRA is recommended as maintenance therapy (every 3 months for 2 years) in combination with mercaptopurine and methotrexate.

Age is a major determining factor for toxicity. ATRA can cause side effects such as headache, dryness of the mouth and skin, skin rashes, and increased cholesterol and triglycerides (blood level).

ATO was originally used as second-line therapy for APL, though because of its low toxicity and the fact that it is well tolerated, it is now used as a first-line drug. It can be administered alongside ATRA in APL patients who have had their first relapse after treatment with ATRA + chemotherapy. ATO does not need to be given together with chemotherapy.

The side effects of ATO are mild and include fatigue, nausea, diarrhea, abdominal pain, and peripheral neuropathy. It has also been shown to cause problems with heart rate, which is why it is recommended that patients be monitored for cardiac function while receiving the treatment.