Treating patients with pediatric leukemia with a liposomal formulation of anthracycline-based chemotherapy at a more intense-than-standard dose during initial treatment may result in high survival rates without causing any added heart toxicity, according to a new study.

Acute myeloid leukemia (AML) is the second most common form of leukemia in children. It is a blood cancer that makes a large number of abnormal white blood cells that crowd out other healthy blood cells over time, which leads to infection, anemia, and excessive bleeding.

The first line of treatment for AML, known as induction therapy, is anthracyclines, which are usually received soon after diagnosis. Standard induction therapy regimens in children typically consist of three days of an anthracycline such as daunorubicin or idarubicin and 7 to 10 days of another chemotherapy such as cytarabine. Long-term survival is achieved by about 60%-70% of children with AML with this combination of drugs.

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Recent evidence has suggested that increasing the intensity of induction treatment might improve remission rates and perhaps overall survival in AML patients, but anthracycline has dose-related toxicity in children. This toxicity particularly affects the developing heart muscle.

To increase effectiveness but reduce cardiac risk, researchers are investigating a liposomal formulation of the anthracycline daunorubicin (L-DNR) that allows for more targeted delivery of the drug in the cancerous cells. It also diffuses at a slower pace in the body, so it has a lower accumulation in the heart.

“We know that the standard induction treatment regimen is effective in pediatric leukemia patients, but recognize that the toxicities associated with this therapy can be damaging to young patients who are still growing and developing,” said lead study author Ursula Creutzig, MD, of the Hannover Medical School in Germany. “This unique formulation of daunorubicin might offer us a way to effectively manage AML in these young patients while reducing their risk of experiencing the acute and long-term toxicities associated with traditional regimens.”

To evaluate this hypothesis, Dr. Creutzig and a team of researchers initiated a trial to determine if L-DNR at intensified dosages in child and adolescent patients would improve their outcomes without added treatment-related acute and long-term cardiotoxicity. Between 2004 and 2010, 521 patients under 18 years of age were randomly assigned to treatment with either L-DNR or idarubicin induction therapy. Patients treated with L-DNR received a higher dose (80 mg/m²/day/x3) than the equivalent dose of idarubicin (12 mg/m²/day/x3) during induction.

After a 5-year observational period, researchers noted similar results in both treatment arms (76% overall survival in the L-DNR group vs 75% in the idarubicin group). The probability of event-free survival (or pEFS) was also similar in the L-DNR (59%) and idarubicin groups (53%), as were pEFS results for standard risk (72% for L-DNR vs 68% for idarubin) and high-risk patients (51% vs 46%, respectively). This study was published in Blood (2013; doi: 10.1182/blood-2013-02-484097).