One-Third Cure Rate in First-Ever Pediatric Relapsed AML Trial

January 18, 2013

By Anne Harding

NEW YORK (Reuters Health) Jan 18 - Over a third of children with relapsed acute myeloid leukemia (AML) can be cured, a new study from the International BFM Study Group demonstrates.

Relapse occurs in up to 40% of pediatric patients with AML, Dr. Gertjan J. L. Kaspers of VU University Medical Center in Amsterdam and his colleagues state in their report, published January 14 in the Journal of Clinical Oncology.

Overall survival after relapse ranges from 16% to 34% -- but there have been no randomized trials until now, so many questions remain about how these children should be treated, Dr. Kaspers and his team say.

Fludarabine, cytarabine and granulocyte-colony stimulating factor (FLAG) are commonly used for induction. It's unclear whether adding anthracyclines to FLAG helps survival after relapse. Anthracyclines at high doses can be cardiotoxic, the researchers add, but research suggests that liposomal daunorubicin (DNX, DaunoXome) may be safer.

To investigate whether DNX would improve survival in children with relapsed AML receiving reinduction treatment with FLAG, the researchers randomly assigned 394 patients to FLAG alone or FLAG plus DNX.

The complete remission rate was 64% overall, and four-year overall survival was 38%. At day 28 of treatment, 80% of patients in the FLAG/DNX group had good bone marrow status (defined as 20% or fewer leukemic blasts), compared to 70% of patients on FLAG alone (p=0.04). Complete remission was 69% for patients on FLAG/DNX and 59% for FLAG only (p=0.07), although overall survival was similar.

But among patients with core-binding factor (CBF) AML, the probability of overall survival was 82% for the FLAG/DNX patients and 58% with FLAG (p=0.04).

About 20% of patients with pediatric relapsed AML have CBF-AML, Dr. Kaspers told Reuters Health via email. "There is data from my own laboratory that these patients have AML cells that are more chemosensitive," he said.

Based on the findings, all patients with relapsed AML should be treated with DaunoXome plus FLA, Dr. Kaspers said. "We decided to leave out "G" because there is now evidence that G-CSF does not add to the combination of fludarabine and cytarabine."

"Working according to a protocol already improves care and thus outcome," the researcher said via email. There is data to "strongly suggest" that DaunoXome is less toxic than other anthracyclines, he added, and it should be the first choice of these drugs for treating leukemias given its myelosuppressive effect.

Dr. Kaspers and his colleagues are now planning a randomized trial to compare FLA-DaunoXome to FLA-DaunoXome plus Mylotarg.

SOURCE: http://bit.ly/10EhqVV

J Clin Oncol 2013.

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