AML treatment guidelines 2017

This review outlined guidelines for the treatment of acute myeloid leukemia (AML).

In AML, too many stem cells (immature blood cells) develop into abnormal red blood cells, white blood cells, or platelets (cells involved in clotting). Treatment options vary based on the age and condition of the patient, and on the presence of certain genetic mutations (permanent changes) in the leukemia cells. In 2010, the European LeukemiaNet (ELN) brought together a panel of experts to make recommendations for the diagnosis and treatment of AML. The guidelines were updated in 2017.

The current article outlined the updated recommendations of the ELN.

The panel recommends that at diagnosis all patients be tested for genetic mutations. In particular, patients should be screened for mutations in the NPM1, CEBPA, RUNX1, and FLT3 genes. The presence of mutations can help in the prediction of prognosis (outcome). Age, health, and other diseases can also help in predicting outcome. Based on these factors, patients can be classified as having favorable, intermediate, or adverse AML. This can guide choice of treatment.

If a patient is in good condition, they can be considered for intensive induction chemotherapy (treatment to induce remission, or no sign of disease). This is generally 3 days of an anthracycline (such as daunorubicin) and 7 days of cytarabine (Cytosar-U). This is known as the 7+3 regimen. The panel recommends a daunorubicin (Cerubadine) dose of more than 60 mg/m² (for younger patients) and a cytarabine dose of 100 mg/m². The 7+3 regimen leads to complete remission (CR) in 60-80% of younger adults and 40-60% of older adults (over 60 years). Lower-dose cytarabine can lead to CR in 15-25% of older patients who cannot undergo standard induction therapy.

In patients with different mutations, other treatments can be included. Midostaurin and chemotherapy significantly increased CR rates in patients with an FLT3 mutation. Midostaurin is a treatment that blocks FLT3.

After induction therapy, patients should undergo consolidation therapy. In fit patients, this could include 1000-3000 mg/m² of cytarabine for up to four cycles (six doses per cycle). Combinations of other chemotherapies have also been shown to be effective. Patients may also undergo one cycle of high-dose chemotherapy followed by stem cell transplantation (SCT). The stem cells should come from a donor (such as a sibling). SCT is usually recommended in patients with more than a 35% risk of relapse.

Patients should be monitored for minimal residual disease (MRD, remaining cancer cells). Patients with continuing MRD or increasing MRD can begin therapy (such as further chemotherapy) or plan to have SCT.

Patients planning to undergo SCT first receive high-dose chemotherapy. Older patients or those with multiple other conditions may choose reduced intensity chemotherapy. 

Patients who relapse or who do not respond to treatment (known as refractory disease) should consider taking part in a clinical trial. A further course of intensive chemotherapy can lead to a second CR in roughly 55%. SCT may also benefit. Studies have noted that a short course of chemotherapy (such as fludarabine, cytarabine, and amsacrine) before reduced intensity chemotherapy and SCT leads to CR rates of 70-90%. 4-year survival rates were noted between 32% and 45%.

New treatments are being explored in clinical trials. These include newer forms of current treatments, and targeted immunotherapies. These are treatments that target specific molecules involved in cancer growth. They can also stimulate the immune system to fight the cancer cells.

This review outlined the recommendations for AML treatment from the ELN.