Less Toxic Induction Tx for Pediatric AML Looks Good in Trials


Induction therapy for pediatric acute myeloid leukemia (AML) is effective, but because it involves anthracyclines it puts these young patients' hearts at risk of damage, leading researchers to look for equally effective treatments without the cardiotoxicity.

German investigators believe they may have found it in a liposomal (or lipid-based) formulation of the anthracycline daunorubicin, known as L-DNR. This formulation is more targeted, and it spreads throughout the body more slowly, meaning that less of the drug can build up in the heart muscle.

The study's lead author, Ursula Creutzig, MD, of the Hannover Medical School in Germany said:

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. 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.


Researchers recruited 521 patients between 2004 and 2010 who were under 18. They were randomized to receive either L-DNR or idarubicin induction therapy. Both arms of the study were also administered cytarabine and etoposide, and all patients received maintenance treatment (unless they went on to have a stem cell transplantation).

In a five-year follow-up, investigators saw similar rates in:

  • Overall survival (76 percent in the L-DNR arm compared to 75 percent in the idarubicin arm)
  • The probability of event-free survival (59 percent versus 53 percent)
  • The probability of event-free survival for standard risk patients (72 percent versus 68 percent)
  • The probability of event-free survival for high-risk patients (51 percent versus 46 percent)

While the numbers were very similar in terms of overall survival and event-free survival, the treatments were also similar in terms of safety and tolerability profiles.

Added Dr. Creutzig:

These findings signal an important step forward in our goal to identify treatments that can give pediatric patients the best chance for long-term survival with minimal toxic side effects, and we believe the approach could have a number of extended applications. For example, this treatment formulation may be appropriate to use in adults or elderly patients to reduce the toxicity profile, or it may be of value for other malignant diseases in both children and adults. We look forward to further investigating L-DNR as the standard anthracycline induction treatment in future studies. 

The study has been published in Blood, the journal of the American Hematology Society.

Source: MNT

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