Children's Oncology Group's 2013 blueprint for research: acute myeloid leukemia

Abstract

For the 365 children diagnosed with acute myeloid leukemia in the US annually, 5-year survival for patients on COG trials with low, intermediate, and high risk disease is 83%, 62%, and 23%, respectively. Recent advances include improved therapeutic stratification, improved survival with dose intensification, and further elucidation of the heterogeneity specific to childhood AML. These discoveries now guide current strategy incorporating targeted agents to pathways specific to childhood AML as well as evaluating methods to increase the sensitivity of the leukemic stem cell, first in Phase II feasibility trials followed by Phase III efficacy trials of the most promising agents. Acute myeloid leukemia in children, though with similar subgroups to adults, remains uniquely different based upon quite different prevalence of subtypes as well as overall response to therapy. The Children's Oncology Group's research agenda builds upon earlier efforts to better elucidate the leukemogenic steps distinct to childhood AML in order to more scientifically develop and test novel therapeutic approaches to the treatment and ultimate cure for children with this disorder. Pediatr Blood Cancer 2013; 60: 964-971. © 2012 Wiley Periodicals, Inc.

Fig. 1

Overal survival–incremental improvements over the last 40 years in COG and legacy trials in childhood AML.

Fig. 2

Overall survival for patients enrolled on two consecutive COG AML trials for newly diagnosed patients. CCG-2961 (pre- and post-supportive care amendments) and AAML03P1. CCG-2961 utilized the intensive timing approach and AAML03P1 applied the dose-intensive approach for induction treatment (This research was originally published in Cancer [3]).

Fig. 3

Risk group reclassification incorporating minimal residual disease assessment after induction therapy. This was found to only be significantly prognostic in the previously defined intermediate risk group and now allows improved prognostic classification and improved therapeutic stratification in the current COG trail, AAML1031.

Fig. 4

Relapse risk and relapse-free survival curves illustrate that regardless of the timing of minimal residual disease (MRD) detection, once found it persists as a prognostic factor regardless of whether it later is negative (This research was originally published in Blood [8]). Residual disease (RD) groups: RD positive–MRD detected at end of therapy. NO RD–MRD not detected at end of induction, during therapy, nor at end of therapy. RD negative but previously positive—Negative at the end of therapy but among the regimen-specified monitoring points during therapy, there was at least one positive MRD finding.