Increased Survival Disparities Among Children and Adolescents & Young Adults with Acute Myeloid Leukemia: A Dutch Population-Based Study
Authors: Schulpen Maya , Goemans Bianca F. , Kaspers Gertjan J.L. , Raaijmakers Marc H.G.P. , Zwaan Christian M. , Karim-Kos Henrike E. 
Published: November 2021

Abstract
Introduction: For many cancers, adolescent and young adult (AYA) patients have a poorer prognosis than pediatric patients. This study compares long-term survival outcomes of children and AYAs diagnosed with acute myeloid leukemia (AML) in the Netherlands. This has not been done before despite the availability of high-quality data collected by the nationwide, population-based Netherlands Cancer Registry (NCR).
Methods: Data on all AML patients aged 0-39 years, diagnosed between 1990-2015, were obtained from the NCR (N=2058). Relative (disease-specific) survival was estimated for all patients, children (0-17 years), and AYAs (18-39 years) using the traditional cohort approach. Early mortality was defined as death within 30 days of diagnosis. Multivariable analyses were performed using generalized linear models (excess mortality) and logistic regression (early mortality).
Results: The prognosis of Dutch AML patients below the age of 40 years has improved considerably during the past decades with 5-year relative survival rates increasing from 39% in 1990-1999 to 61% in 2010-2015 (p trend&lt;0.01). AYAs had a substantially lower 5-year relative survival than children (43% vs. 57%, Figure). Although survival increased over time in both age groups, the improvement was more pronounced among children. Therefore, the survival gap was largest in the most recent period. In 2010-2015, 5-year relative survival was 74% for children compared to only 54% for AYAs. More detailed analyses showed that 1-9 year old children had the best prognosis with a 5-year relative survival of 84% in 2010-2015. With respect to the AML subtypes, core-binding factor (CBF) leukemia was more structurally tested and registered as from 2001. Within the group of patients diagnosed with CBF leukemia since 2001 (children: N=68, AYAs: N=68), children also had a better 5-year relative survival than AYAs (84% vs. 75%, not statistically significant).
When compared to children, the excess risk of dying due to AML was 70% higher in AYAs [95% confidence interval (95% CI), 47%-97%] after adjustment for follow-up time, sex, period of diagnosis, and stem cell transplantation. The excess hazard ratios (HRs) of mortality were 2.0 (95% CI, 1.6-2.4) for 18-29 year olds and 2.1 (95% CI, 1.7-2.6) for 30-39 year olds, using 1-9 year olds as reference.
Early mortality declined over time from 9% to 4% (p trend&lt;0.01), and did not differ between children and AYAs. However, multivariable-adjusted odds ratios (ORs) of early death were doubled when comparing older age groups to 1-9 year olds.
Conclusions: AYAs diagnosed with AML in the Netherlands between 1990 and 2015 had a worse prognosis than pediatric patients. The survival disparity seemed most evident in recent years, suggesting that improvements in care resulting in better outcome for children have not led to equal benefits for AYAs yet.
Figure 1 Figure 1.

Disclosures
No relevant conflicts of interest to declare.