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What is ATRA and ATO therapy?
ATRA and ATO therapy is a combination treatment of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) which is now recognised as the first-line treatment for acute promyelocytic leukaemia (APL). A first-line treatment is accepted as the best initial treatment for a given type and stage of a disease.
ATRA and ATO are not chemotherapy drugs, but drugs called differentiating agents. They encourage the promyelocytic cells to differentiate (mature) into normal white blood cells. They also have complementary actions in that ATRA breaks down the PML-RARA gene and ATO encourages the abnormal APL cells to self-destruct.
To achieve remission (induction therapy) and re-enforce remission (consolidation therapy):
- Patients with low- to intermediate-risk APL can be given ATRA plus ATO
- Patients with high-risk APL can be given either of the following regimens because studies have shown that neither was superior to the other:
- ATRA plus ATO with cytoreductive chemotherapy such as cytarabine (cytoreductive means that the chemotherapy reduces the number of cells, which in the case of APL are abnormal promyelocytes)
- ATRA plus an anthracycline
However, using ATO for high-risk patients may be difficult because the EMA has only approved ATO for low- to intermediate-risk APL, but not for high-risk APL as of yet.
Method of administration:
ATRA and ATO therapy should be started as soon as possible and monitored under the supervision of a doctor experienced in the use of chemotherapeutic agents who will explain the use of this combination therapy to you.
All patients will start induction treatment as an inpatient but very few will remain inpatients all the way through the eight weeks it takes to deliver ATO induction. The latter part of these weeks will be given to you as an outpatient once you are completely stable and responding well to treatment.
Depending on the Haematology Unit in your hospital, you will probably be able to have consolidation treatment on an outpatient basis. As this is a combination treatment, your consultant will decide the best combination regimen in terms of the doses and the frequency of administration for you.
In addition to induction treatment, patients with APL require supportive care such as blood product transfusions to maintain the platelet count and the blood clotting indicators as normal as possible. Blood chemical levels (particularly potassium and magnesium which are important for electrical conduction in the heart) will be monitored closely. Sometimes it is necessary to also give potassium and/or magnesium supplements.
For consolidation treatment, patients will be given seven courses of ATRA (with a two-week break between courses) and four consolidation courses of ATO (with a four-week break between courses) are recommended by the latest guidelines.
Common side effects:
- Differentiation syndrome – This occurs during the first weeks of treatment when the differentiating agents ATRA and ATO start allowing the promyelocyte cells to mature. It is usually associated with a rise in the white blood cell count.
- Pseudotumour cerebri – This non-serious increase in pressure in the skull is seen with both ATRA and ATO and is more common when both drugs are given together.
- Heart rhythm disturbance (prolongation of the QT interval) which can be seen on the ECG.
Other side effects include:
- Harmful liver effects
- Mood changes
- Fatigue
- Nausea and vomiting
- Nausea and vomiting
- Diarrhoea and/or constipation
- Changes to skin
- Bone and muscle pain
- Numbness and tingling in fingers and toes
Who was involved in the production of the booklet?
This booklet has been updated by our Patient Information Writer, Isabelle Leach, and peer reviewed by Dr Steve Knapper. We are also grateful to leukaemia patients Bruce Bain and John Pointon for their valuable contributions.
If you would like more information about ATRA and ATO as a treatment for APL, you can download the booklet from our information booklets page here.