Treatment of Acute Promyelocytic Leukemia (APL)

Prompt diagnosis and treatment of acute promyelocytic leukemia (APL), a subtype of acute myeloid leukemia (AML), is very important because people with APL can quickly develop life-threatening blood-clotting or bleeding problems if not treated. In fact, treatment might need to be started even if the diagnosis of APL is suspected but hasn't been confirmed yet by lab tests.

 APL treatment differs from the treatment of most other types of AML. The most important drugs for treating APL are non-chemo drugs called differentiating agents, including all-trans-retinoic acid (ATRA) and arsenic trioxide (ATO). Other treatments might include chemotherapy (chemo) and transfusions of platelets or other blood products.

Treatment of APL is typically divided into 3 phases:

• Induction (remission induction)
• Consolidation (post-remission therapy)
• Maintenance

Induction

The goal of induction, the first part of treatment, is to get the number of leukemia cells to very low levels, putting the APL into remission. The most important drug in the initial treatment of APL is all-trans-retinoic acid (ATRA). This is usually combined with one of these:

• Arsenic trioxide (ATO), another non-chemo drug. For some people who have a higher risk of APL coming back after treatment, the targeted drug gemtuzumab ozogamicin (Mylotarg) might be added as well.
• Chemotherapy with an anthracycline drug (daunorubicin or idarubicin). For some people at high risk of APL coming back after treatment, the chemo drug cytarabine (ara-C) might be added as well.
• Chemotherapy (an anthracycline) plus ATO

ATRA plus ATO is the preferred treatment in people at lower risk of the leukemia coming back, as it tends to have fewer side effects. The remission rate with these 2 drugs alone is very high.

Chemo or gemtuzumab ozogamicin is more likely to be included in treatment if this risk is higher or if the white blood cell count goes higher.

A bone marrow biopsy with repeat genetic testing is usually done about a month or so after starting treatment, to see if the leukemia is in remission. Induction is typically continued until the APL is in remission, which might take up to 2 months.

Consolidation (post-remission therapy)

Once APL is in remission, consolidation therapy is needed to keep it in remission and try to get rid of the remaining leukemia cells. Which drugs are used depends on what was given for induction, as well as other factors. People typically get some of the same drugs they got during remission, although the doses and timing of treatment might be different. Some of the options include:

• ATRA plus ATO (Gemtuzumab ozogamicin is rarely needed once someone is in remission.)
• ATRA plus chemo (typically using an anthracycline such as idarubicin or daunorubicin)
• Chemo alone (typically with an anthracycline plus cytarabine)

Consolidation typically lasts for at least several months, depending on the drugs being used.

Maintenance

For some people, especially those at higher risk of the APL coming back, consolidation may be followed by maintenance therapy, which uses lower doses of drugs over a longer period of time. People who have a lower risk of the leukemia coming back and who have had a good response (molecular remission) to ATRA plus ATO generally do not need maintenance therapy.

Options for maintenance therapy are ATRA alone, or ATRA along with chemo (6-mercaptopurine (6-MP) and/or methotrexate). Maintenance therapy is typically given for about a year.

Treating APL that doesn't go away or comes back

Treatment for APL that doesn't go away or that comes back after initial treatment is discussed in If Acute Myeloid Leukemia (AML) Doesn't Respond or Comes Back After Treatment.