Real-world generalizability of clinical trial cytomolecular risk in pediatric acute myeloid leukemia: a report from the REAL-AML cohort

Daniel J Zheng; Gary Hettinger; Catherine Aftandilian; Kira Bona; Emi H Caywood; Anderson B Collier; Caitlin W Elgarten; Cody Gathers; Taumoha Ghosh; M Monica Gramatges; Meret Henry; Yuan-Shung V Huang; Yimei Li; Craig Lotterman; Kelly Maloney; Amir Mian; Tamara P Miller; Arunkumar Modi; Rajen Mody; Elaine Morgan; Regina Myers; Haley Newman; Jose Ortiz; Alix E Seif; Caroline Smith; Jamie Stokke; Xin Wang; Naomi Winick; Jennifer J Wilkes; Victor Wong; Richard Aplenc; Kelly D Getz

doi:10.1093/jnci/djaf234

Real-world generalizability of clinical trial cytomolecular risk in pediatric acute myeloid leukemia: a report from the REAL-AML cohort

J Natl Cancer Inst. 2025 Aug 20:djaf234. doi: 10.1093/jnci/djaf234. Online ahead of print.

Authors

Daniel J Zheng¹, Gary Hettinger², Catherine Aftandilian³, Kira Bona⁴, Emi H Caywood^{5

6}, Anderson B Collier⁷, Caitlin W Elgarten¹, Cody Gathers⁸, Taumoha Ghosh⁹, M Monica Gramatges¹⁰, Meret Henry¹¹, Yuan-Shung V Huang¹², Yimei Li^{1

13}, Craig Lotterman¹⁴, Kelly Maloney¹⁵, Amir Mian¹⁶, Tamara P Miller^{17

18}, Arunkumar Modi¹⁹, Rajen Mody²⁰, Elaine Morgan²¹, Regina Myers¹, Haley Newman¹, Jose Ortiz^{1

13}, Alix E Seif¹, Caroline Smith²², Jamie Stokke²³, Xin Wang²⁴, Naomi Winick²², Jennifer J Wilkes²⁵, Victor Wong²⁶, Richard Aplenc^{1

13}, Kelly D Getz¹³

Affiliations

¹ Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
² Department of Population Health, New York University Grossman School of Medicine, New York, NY, USA.
³ Department of Pediatrics, Division of Pediatric Hematology/Oncology, Stanford University, Palo Alto, CA, USA.
⁴ Department of Pediatric Oncology, Division of Population Sciences, Dana-Farber Cancer Institute, Boston, MA, USA.
⁵ Department of Pediatrics, Thomas Jefferson University, Philadelphia, PA, USA.
⁶ Nemours Children's Health, Wilmington, DE, USA.
⁷ Nemours Children's Health, Jacksonville, FL, USA.
⁸ Division of Cardiology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
⁹ Department of Pediatrics, Division of Pediatric Hematology/Oncology, Primary Children's Hospital/University of Utah, Salt Lake City, UT, USA.
¹⁰ Texas Children's Hospital, Baylor College of Medicine, Houston, TX, USA.
¹¹ Department of Pediatrics, Division of Pediatric Hematology/Oncology/BMT, Children's Hospital of Michigan, Detroit, MI, USA.
¹² Department of Biomedical and Health Informatics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
¹³ Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
¹⁴ Ochsner Medical Center for Children, New Orleans, LA, USA.
¹⁵ Children's Hospital Colorado and the Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO, USA.
¹⁶ Division of Pediatric Hematology/Oncology, Dell Children's Hospital, University of Texas-Austin, TX, USA.
¹⁷ Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Atlanta, GA, USA.
¹⁸ Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA.
¹⁹ University of Arkansas for Medical Sciences, Division of Pediatric Hematology Oncology, Arkansas Children's Hospital, Little Rock, AR, USA.
²⁰ University of Michigan, Ann Arbor, MI, USA.
²¹ Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA.
²² Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX, USA.
²³ Children's Hospital of Los Angeles, Los Angeles, CA, USA.
²⁴ Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
²⁵ Department of Pediatrics, University of Washington School of Medicine, Division of Hematology/Oncology, Seattle Children's Hospital, Seattle, WA, USA.
²⁶ Division of Pediatric Hematology Oncology, Rady Children's Hospital San Diego, San Diego, CA, USA.

Abstract

Cytomolecular features critical for risk-stratified treatment determination in pediatric acute myeloid leukemia (AML) were expanded in Children's Oncology Group (COG) Phase III trial AAML1831 based on previous trials. It remains unknown whether the cytomolecular risk profiles are generalizable to the real-world. We addressed this knowledge gap using a nationally representative real-world cohort of 913 pediatric AML patients. Distributions of cytomolecular risk profiles and individual markers were comparable for trial-enrolled and non-enrolled patients, as well as across social drivers of trial enrollment (race/ethnicity, language, insurance, acuity). Compared to patients with only favorable cytomolecular markers (4-year OS 89.48%; 95% CI: 84.46%-92.95%), patients with both favorable and unfavorable (hazards ratio [HR] = 2.49, 95% CI : 1.18-5.23), neutral (HR = 4.33, 95% CI : 2.75-6.82), and only unfavorable (HR = 5.80, 95% CI: 3.70-9.11) markers all had increased hazards of death. Cytomolecular risk informed by trial data appears to be generalizable to the real-world setting in pediatric AML.

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Abstract

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