Abstract
Background: The optimal setting to treat AYA patients remains a complex decision involving access to different treatment regimens, clinical trial availability, and appropriate psychosocial support. There are data to support that AYA patients with acute lymphoblastic leukemia (ALL) have better outcomes and improved overall survival when treated on pediatric inspired treatment protocols. However, limited data exist for similar patients with AML. We, therefore, sought to assess the variation in outcomes between AML patients within the AYA population treated in our pediatric setting versus adult setting.
Methods: A retrospective review of patients with newly diagnosed AML aged 17-25 years old (n=33) treated at either the Indiana University Simon Cancer Center (n=20) or Riley Hospital for Children at Indiana University Health (n=13) between 2006 and 2018 was completed. All patients in the adult setting received standard induction therapy with the 7+3 (standard-dose cytarabine, anthracycline) regimen, while patients in the pediatric setting received an ADE (daunorubicin, cytarabine, etoposide) backbone +/- investigational agents per clinical trial protocols. Data were analyzed with t-tests using IBM SPSS v25 software. This study was approved by the Indiana University Institutional Review Board.
Results: Median age was 23 years in patients treated in the adult setting (range 19-25) compared with 17 years (range 17-20) in the pediatric setting. As per the most recent NCCN risk classification for AML, patients in the adult setting were classified as 55% poor risk, 35% intermediate risk, and 10% favorable risk; in the pediatric setting, risk classification was 15% poor risk, 62% intermediate risk, and 23% favorable risk. The incidence of FLT3 mutations was n=4 (20%) in the adult setting and none in the pediatric setting. Clinical trial enrollment was markedly lower in the adult setting with no patients enrolled compared with 54% (7/13) enrolled in the pediatric setting. Complete response (CR) was achieved in 85% of patients treated in the adult setting, but only 62% of patients treated in the pediatric setting. Relapse post induction was higher in the pediatric setting (n=6, 46%) compared to the adult setting (n=5, 40%), and median time to relapse was shorter in the pediatric setting (275 days vs. 344 days). During induction, no statistically significant differences in toxicities were found as measured by ICU interventions (dialysis, mechanical ventilation/NIPPV, and/or use of vasopressors) and identified infections (bacteremia, pneumonia, and/or clostridium difficile). Clostridium difficile infections were increased in the adult setting (15% vs. 0%), but identified bacteremia was higher in the pediatric setting (38% vs. 20%).
The median time to allogeneic stem cell transplantation in the adult setting was 117.5 days compared to a median of 223 days seen in the pediatric setting. Incidence of relapse post stem cell transplantation was higher in the adult setting (36% vs. 17%). Proportion of overall survival was 50% (n=10) in the adult setting and 28% (n=8) in the pediatric setting. The highest mortality was seen in poor-risk patients (90%) in the adult setting and intermediate risk patients (62.5%) in the pediatric setting.
A trend was seen towards improved overall survival in the adult setting with median overall survival of 739.5 days in the adult setting compared to 415 days in the pediatric setting (p=0.11). In both settings, patients that proceeded to stem cell transplantation had conferred survival benefit: median 1128 vs. 414.5 days in the adult setting and median 530.5 vs. 486.5 days in the pediatric setting.
Conclusion: Despite having a higher risk population and lower clinical trial enrollment, we found a trend towards higher complete response rate after induction, reduced relapse rate after induction, shorter time to transplant, longer time to relapse post-transplant, improved survival in the transplant population, and improved median overall survival without a clear increase in toxicity in patients treated in our adult setting. This is in contrast to data in ALL, which suggests improved patient outcomes in AYA patients treated with pediatric based regimens. Our data is limited by a small sample size and a single institution experience. Larger, multicenter studies are needed to understand the optimal AML treatment strategy in the AYA population.
No relevant conflicts of interest to declare.
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