Acute Promyelocytic Leukaemia (APL)

Acute promyelocytic leukaemia (APL) is a blood cancer, which affects the myeloid cells, which include red blood cells, platelets and some white blood cells

APL is a rare sub-type of acute myeloid leukaemia (AML). When you have APL, the bone marrow is not able to make enough normal blood cells.

APL is treated in a very different way from other forms of AML, if a patient with APL is given standard treatment, there is a risk of serious problems with their clotting system. Fortunately, it is usually very easy to tell the difference between APL and other types of AML.

Acute promyelocytic leukaemia usually responds very well to treatment and patients with this form of leukaemia have a good chance of being cured.

What causes APL?

The cause of most cases of APL are not known. It is sometimes seen in people who have been treated for other forms of cancer; this only affects a very small percentage of cancer patients. This is known as therapy-related APL (t-APL) and accounts for about 1 in 10 cases of APL; this type of APL is treated in the same way as other cases and responds equally well to treatment.  You cannot catch APL from someone who has it and you cannot pass APL on to your children.

Signs and symptoms of APL

The most common symptoms and their causes are:

  • Anaemia – breathlessness, fatigue
  • Low white cells – frequent, persistent infections
  • Low platelets – bruising and/or bleeding
  • DIC – bruising/bleeding which may be very severe

Diagnosis

APL is diagnosed by tests which may include:

  • Blood tests
  • Bone marrow samples

Other tests may be done

Occasionally, it is not clear from the blood film whether the abnormal cells are promyelocytes. By examining the proteins found on the outside of the cell, called cell markers, it is possible to identify the cells with certainty.

Another test looks for an abnormality called PML-RARA. This is an abnormal “fusion gene” – PML and RARA are two genes which are normally found on different chromosomes. In APL the two chromosomes swap over part of their DNA, which joins the PML and RARA genes together. This test is important because the main drugs used to treat APL work directly on the PML-RARA gene; in the very rare cases of APL without PML-RARA, other treatments can be used.

These tests may be repeated from time to time during your treatment. This is to find out how the APL is responding to treatment.

Treatment

Treatment of patients who are suspected of having APL should be treated immediately, even before the diagnosis is made, because they can quickly develop potentially life-threatening bleeding or blood clotting symptoms. A firm diagnosis of APL using genetic testing can be performed later, and treatment can be discontinued if APL is not confirmed.

Patients with APL are generally subdivided into the following two groups according to their white blood count as treatment recommendations can differ for each group:

 

  • Low- to intermediate-risk: patients with a white blood cell count of 10,000 cells per microlitre of blood or less.
  • High-risk: patients with a white blood cell count of more than 10,000 cells per microlitre of blood.

 

 

Treatment options

First-line treatment

First-line treatment for APL includes all-trans retinoic acid (ATRA), which is an active by- product of vitamin A. ATRA blocks the effect of the PML-RARA gene that prevents the promyelocyte cells maturing into normal white blood cells (differentiation). 

ATRA is not a chemotherapeutic drug and is called a differentiating agent. It is given in combination with another drug in patients with APL to prevent any drug resistance.

ATRA can sometimes be given with chemotherapy drugs called anthracyclines. Anthracyclines, such as daunorubicin and idarubicin, interfere with the DNA and reproduction of white blood cells, including the leukaemia cells. ATRA is given as a capsule, while anthracyclines are given intravenously.

In 2018, NICE approved a drug called arsenic trioxide (ATO) for the first-line treatment of APL in previously untreated patients, with low- to intermediate-risk disease and patients whose APL has returned (relapsed) or did not respond to chemotherapy (refractory). ATO is also a differentiating agent and acts in a similar way to ATRA.

Because differentiating agents have less side effects to chemotherapy drugs, especially anthracyclines, the combination of ATRA and ATO alone is a preferred first-line therapy, particularly as studies found it to be at least as effective as the combination of ATRA and anthracyclines, if not more so, with a reduced risk of disease relapse.

Induction treatment

To achieve remission (induction therapy), the 2019 guidelines from the European Leukaemia Network (European LeukemiaNet) recommend the following regimens:

  • Low-to-intermediate risk patients: ATRA and ATO
  • High-risk patients: Both of the following regimens achieve similar results; however, ATO is not approved for high-risk patients by NICE as yet.
    • ATRA and ATO plus a cytoreductive chemotherapy such as cytarabine. Cytoreductive means that the chemotherapy reduces the number of cells.
    • ATRA plus anthracyclines. The most frequently used regimen being called AIDA.

The treatment for APL that has developed as a consequence of prior chemotherapy is normally similar to APL associated with the PML-RARA gene, although your doctor may choose to use a different drug in this situation.

In addition to induction treatment, patients with APL require supportive care in the form of blood product transfusions to maintain the platelet count and the blood clotting indicators as normal as possible and to prevent the risk of bleeding. 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.

Consolidation treatment

To consolidate remission in patients who have not received chemotherapy-based treatment, four courses of ATO and seven courses of ATRA are recommended. This can usually be given as an outpatient.

For patients who received ATRA and chemotherapy regimens, two to three courses of anthracycline- based chemotherapy should be given for consolidation therapy. This is usually given as an inpatient.

Maintenance treatment

For low- to intermediate-risk patients, maintenance treatment after consolidation with ATO and ATRA is not recommended, but for high-risk patients on ATRA and chemotherapy who are showing clinical benefit, maintenance may be initiated with tablets for two years.

Second-line treatment

First-line treatment is generally successful in most patients with APL. However, for patients who haven’t gone into first remission or who have relapsed, second-line treatment options are available.

Relapse or being refractory to first-line treatment can occur in any patient with APL, regardless of whether they have been treated with ATRA with ATO or ATRA with chemotherapy. However, these events are uncommon in low- to intermediate-risk patients.

The second-line treatment you have for relapsed or refractory APL will depend mainly on which first- line treatment you were given. If you have had ATRA with ATO as first-line treatment, then you will receive ATRA with chemotherapy, and vice-versa (you will be given ATRA with ATO if you had ATRA with chemotherapy as first-line treatment).

In young, fit patients, an autologous stem cell transplant can be performed. With an autologous stem cell transplant, you are given intensive chemotherapy to destroy all the leukaemia cells. However, as the chemotherapy will also kill your own bone marrow cells, you are given a transplant of your own healthy stem cells which were collected before the intensive chemotherapy. However, in patients who were responding well to ATO and then relapsed, a transplant is not always necessary.

 

Side effects

Side effects in patients with APL when treated with ATRA and ATO include:

    • Differentiation syndrome – When the differentiating agents start allowing the promyelocyte cells to mature.
    • Pseudotumour cerebri – A non-harmful increase in pressure in the skull and unrelated to any tumour.

 

  • Hyperleukocytosis – Your white blood cell count is greater than 100,000 per microlitre.
  • Heart rhythm disturbance (prolongation of QTc interval) –
  • Signs of toxicity in the liver –

 

Side effects common with anthracyclines are cardiomyopathy (disease of the heart muscle) and secondary leukaemia.

Other side effects include: 

  • Nausea and vomiting
  • Alopecia
  • Bone marrow suppression (resulting in low levels of white blood cells, red blood cells and platelets)

 

Questions to ask your doctor about APL

We understand going through a blood cancer journey can be difficult. It may help to talk to a close friend or relative about how you are feeling. Here are some questions that may be useful to ask your doctor.

  • How would I know if I had APL?
  • What tests will I need to have?
  • What will the tests show?
  • How long will the results take?
  • How rare is APL?
  • What sort of treatment will I need?
  • How long will my treatment last?
  • What will the side effects be?
  • Is there anything I should or shouldn’t eat?
  • Will I be able to go back to work?
  • Where can I get help with claiming benefits and grants?
  • Where can I get help dealing with my feelings?

 

Further downloads

We have free patient information available for APL patients.

You can download the booklets on our information pages here.

Alternatively, you can have the information delivered free of charge by requesting it through our resources page. 

Patient stories

Support for APL patients

Online support

There is a closed group on Facebook for APL patients. To request to join, click here.

There is also a general leukaemia support group on Facebook which is ran by Leukaemia Care. To request to join, click here.

Offline support groups

There area number of haematology support groups in the UK. Find out more on our support groups page. 

 

Published: January 2020

Review date: January 2023