Collaborative Efforts Driving Progress in Pediatric Acute Myeloid Leukemia

Abstract

Diagnosis, treatment, response monitoring, and outcome of pediatric acute myeloid leukemia (AML) have made enormous progress during the past decades. Because AML is a rare type of childhood cancer, with an incidence of approximately seven occurrences per 1 million children annually, national and international collaborative efforts have evolved. This overview describes these efforts and includes a summary of the history and contributions of each of the main collaborative pediatric AML groups worldwide. The focus is on translational and clinical research, which includes past, current, and future clinical trials. Separate sections concern acute promyelocytic leukemia, myeloid leukemia of Down syndrome, and relapsed AML. A plethora of novel antileukemic agents that have emerged, including new classes of drugs, are summarized as well. Finally, an important aspect of the treatment of pediatric AML--supportive care--and late effects are discussed. The future is bright, with a wide range of emerging innovative therapies and with more and more international collaboration that ultimately aim to cure all children with AML, with fewer adverse effects and without late effects.

Fig 1.

(A) Distribution of genetic abnormalities in pediatric acute myeloid leukemia (AML). Collaborating type I and type II mutations in pediatric AML. The circos plot depicts the frequency of the type II mutations and co-occurrence of type I mutations in patients with de novo pediatric AML. The length of the arch corresponds with the frequency of the type II mutation, and the width of the ribbon corresponds with the percentage of patients who have a specific type I mutation or combination of type I mutations. (B) Overview of co-occurring mutations in pediatric cytogenetically normal (CN) AML (N = 53). Each column represents a single occurrence. A colored field means that the occurrence is positive for a mutation or translocation in the corresponding gene(s). A white field indicates that the occurrence tested negative for a mutation or translocation in the corresponding gene(s). A gray field indicates an occurrence that could not be tested for mutations in the corresponding gene. dm, double mutations; ITD, internal tandem duplication; PTD, partial tandem duplication; sm, small mutations.