Daunorubicin-free Induction Therapy for Standard-risk Childhood Acute Lymphoblastic Leukemia 


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We conclude that daunorubicin is dispensable during induction therapy in children with good early response to treatment.

—André Baruchel, MD

Omitting daunorubicin from induction therapy for children with standard-risk acute B-cell lymphoblastic leukemia (ALL) does not compromise survival and at the same time reduces the risk of associated toxicities, including myelosuppression and cardiac damage, according to results of the large phase III FRALLE 2000-A trial, which were reported at the 54th Annual Meeting of the American Society of Hematology (ASH) in Atlanta.

Induction with or without daunorubicin achieved a 5-year event-free survival of about 93%. Overall survival was 97% in children treated with anthracycline-free induction therapy vs 98% among those who received daunorubicin during induction.

First Scientific Proof

In fact, many centers in the United States and some in Europe no longer use daunorubicin as initial therapy, but this study is important because it provides the first scientific proof in the modern era for omitting this drug, noted lead author André Baruchel, MD, Head of the Department of Pediatric Hematology at the Robert Debré University Hospital in Paris.

“This study shows that daunorubicin can be safely omitted from initial treatment in standard-risk B-cell lineage ALL children, who constitute the majority of ALL patients, without negatively affecting their immediate outcome. Removing harmful chemotherapy can minimize their risk of heart damage later in life,” Dr. Baruchel stated.

Standard-risk ALL is highly curable in children, with an estimated 5-year survival of 90%. Some groups use anthracyclines during induction, while others don’t, and no randomized trials have been published since 1991 to resolve this issue, Dr. Baruchel explained.

“Only three older studies [of anthracyclines in this setting]are included in a specific Cochrane Review, and these studies used different supportive care measures. Now we use increased doses of dexamethasone. Although daunorubicin may reduce relapses, it is not clear if it improves survival in standard-risk ALL, and causes myelosuppression and cardiac events,” he continued.

Current Study Details

In one of the largest studies to date of anthracycline-based induction therapy in childhood ALL, 1,128 patients were randomly assigned to standard induction (vincristine, dexamethasone, and native Escherichia coli asparaginase [Elspar in the United States, Kidrolase in France, where the FRALLE 2000-A study was primarily conducted]) with or without daunorubicin. All patients received delayed doxorubicin-based intensification therapy, followed by 24 months of maintenance therapy.

At the ASH meeting, Dr. Baruchel reported findings at a median follow-up of 69 months. Both groups were quite similar at baseline for demographic and disease characteristics.

Complete response to chemotherapy was similar between treatment arms: 99.7%. No significant difference was seen in overall survival, event-free survival, and complete response. Five-year event-free survival was 92.6% with daunorubicin and 92.8% without it. Overall survival rates were 97.3% and 98%, respectively, for the two groups.

“The number of events was almost identical in both arms. This is nearly too good to be true,” he said.

The only significant difference in grade 3 or 4 toxicity was the incidence of neutropenia, which was a median of 22 days with daunorubicin and 25 days without.

“We conclude that daunorubicin is dispensable during induction therapy in children with good early response to treatment. These children still undergo intensive treatment with a long maintenance therapy of 24 months,” he said. ■

Disclosure: Dr. Baruchel reported no potential conflicts of interest.

Reference

1. Baruchel A, Petit A, Leblanc T, et al: Daunorubicin or not during the induction treatment of childhood standard-risk B-cell precursor acute lymphoblastic leukemia: The randomized FRALLE 2000-A protocol. 2012 ASH Annual Meeting. Abstract 135. Presented December 9, 2012.


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