Treatment guidelines for acute myeloid leukemia

This study summarizes key guidelines on the first-line management of acute myeloid leukemia (AML).

AML is a type of cancer in which the bone marrow makes abnormal myeloblasts (a type of white blood cell). An estimated 21,380 people will be diagnosed with AML in 2017. The average age at diagnosis is 67 years. As the population ages, the incidence of AML seems to be increasing. The National Comprehensive Cancer Network recently summarized key guidelines on the management of AML.

Induction therapy is the first phase of treatment. The aim of induction therapy is to achieve remission (no sign of active disease).The recommended induction therapy for AML patients under the age of 60 involves a combination of chemotherapies. These are typically cytarabine (Cytosar-U) with either idarubicin (Idamycin) or daunorubicin (Cerubidine). In an analysis of 29 trials, both high- dose daunorubicin and idarubicin resulted in 5-year survival rates between 40 and 50%. Another study including 652 patients examined adding cladribine (Leustatin) to induction therapy with cytarabine and daunorubicin. This combination improved remission and survival rates.

Patients under the age of 45 may benefit from induction therapy with high-dose cytarabine with idarubicin or daunorubicin. High-dose cytarabine may also be recommended for those with high-risk disease. This includes patients with genetic abnormalities, such as an FLT3 mutation (permanent change). AML patients with an FLT3 mutation may also receive standard-dose cytarabine with daunorubicin and midostaurin (Rydapt). Younger AML patients may also receive fludarabine (Fludara) as part of induction therapy.

After induction therapy, patients should have a bone marrow evaluation. This test is to determine whether remission has been achieved. Further treatments are based on the response to induction. Patients who see a complete response (no sign of active disease) will undergo consolidation therapy. The aim of this therapy is to maintain remission. Patients who do not achieve a complete response may repeat the same or intensified induction therapy. Participating in a clinical trial or undergoing stem cell transplantation are also options.

The recommended consolidation therapy for patients with favorable- or intermediate-risk disease is 3 to 4 cycles of high-dose cytarabine. Additional midostaurin is an option for those with intermediate-risk disease. Stem cell transplantation may also be considered.  Patients with chromosomal or genetic abnormalities are considered to be higher risk. High-risk patients should consider adding midostaurin to high-dose cytarabine. These patients should also search for a potential matched donor for stem cell transplantation.

Patients older than 60 may or may not be able to undergo intensive induction therapy. This depends on factors such as additional medical conditions and age. Patients who are not able to undergo intensive induction therapy may receive lower-intensity therapy. This can involve up to 3 to 4 cycles with the chemotherapies azacytidine (Vidaza) and decitabine (Dacogen) or low-dose cytarabine. Other options include participation in a clinical trial or best supportive care.

Induction therapy for newly diagnosed patients over 60 with favorable-risk disease may be the same as for patients under 60. This would include standard-dose cytarabine. Lower-intensity induction therapy may be offered to patients at higher risk. Standard-dose cytarabine with daunorubicin and midostaurin is an effective treatment option for patients with an FLT3 mutation. It is not yet clear whether standard-dose cytarabine should be offered with clofarabine (Clolar).

After induction therapy all patients should have a repeat bone marrow evaluation. Patients with residual disease may receive additional cytarabine at a standard dose. This may be combined with idarubicin, daunorubicin, mitoxantrone or midostaurin. Reduced-intensity chemotherapy followed by stem cell transplantation is also an option. This treatment should be started within 4 to 6 weeks after the start of induction therapy. Clinical trial participation and best supportive care are also options.

Patients who achieve complete response after intensive induction therapy may receive further consolidation with the same therapies. Older patients in their first remission may consider reduced-intensity chemotherapy followed by stem cell transplantation. Patients who received lower-intensity therapy may continue consolidation with the same therapies. A clinical trial, reduced-intensity transplant, or observation are also appropriate.

This study outlined the National Comprehensive Cancer Network treatment guidelines for AML.