Rationale and design of the Children's Oncology Group study AAML1831 integrated cardiac substudies in pediatric acute myeloid leukemia therapy.

Autor:	Leger KJ; Division of Pediatric Hematology/Oncology, Seattle Children's Hospital, University of Washington, Seattle, WA, United States., Robison N; Division of Pediatric Hematology/Oncology, Seattle Children's Hospital, University of Washington, Seattle, WA, United States., Narayan HK; Division of Cardiology, Department of Pediatrics, Rady Children's Hospital San Diego, University of California San Diego, La Jolla, CA, United States., Smith AM; Division of Cardiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States., Tsega T; Division of Cardiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States., Chung J; Division of Cardiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States., Daniels A; Division of Cardiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States., Chen Z; Division of Cardiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States., Englefield V; Division of Cardiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States., Demissei BG; Division of Cardiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States., Lefebvre B; Division of Cardiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States., Morrow G; Division of Cardiology, Children's Healthcare of Atlanta, Atlanta, GA, United States., Dizon I; Division of Cardiology, Seattle Children's Hospital, Seattle, WA, United States., Gerbing RB; Children's Oncology Group, Monrovia, CA, United States., Pabari R; Division of Hematology/Oncology, The Hospital for Sick Children, Toronto, ON, Canada., Getz KD; Division of Oncology, Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania., Aplenc R; Division of Oncology, Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania., Pollard JA; Division of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, United States.; Department of Pediatrics, Harvard Medical School, Boston, MA, United States., Chow EJ; Division of Pediatric Hematology/Oncology, Seattle Children's Hospital, University of Washington, Seattle, WA, United States.; Clinical Research and Public Health Sciences Divisions, Fred Hutchinson Cancer Center, Seattle, WA, United States., Tang WHW; Department of Cardiovascular Medicine, Heart Vascular and Thoracic Institute, Cleveland Clinic, Cleveland, OH, United States., Border WL; Division of Cardiology, Children's Healthcare of Atlanta, Atlanta, GA, United States.; Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, United States., Sachdeva R; Division of Cardiology, Children's Healthcare of Atlanta, Atlanta, GA, United States.; Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, United States., Alonzo TA; Children's Oncology Group, Monrovia, CA, United States.; Keck School of Medicine, University of Southern California, Los Angeles, CA, United States., Kolb EA; Nemours Center for Cancer and Blood Disorders, Alfred I. DuPont Hospital for Children, Wilmington, DE, United States., Cooper TM; Division of Pediatric Hematology/Oncology, Seattle Children's Hospital, University of Washington, Seattle, WA, United States., Ky B; Division of Cardiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in cardiovascular medicine [Front Cardiovasc Med] 2023 Dec 01; Vol. 10, pp. 1286241. Date of Electronic Publication: 2023 Dec 01 (Print Publication: 2023).
DOI:	10.3389/fcvm.2023.1286241
Abstrakt:	Background: Pediatric acute myeloid leukemia (AML) therapy is associated with substantial short- and long-term treatment-related cardiotoxicity mainly due to high-dose anthracycline exposure. Early left ventricular systolic dysfunction (LVSD) compromises anthracycline delivery and is associated with inferior event-free and overall survival in de novo pediatric AML. Thus, effective cardioprotective strategies and cardiotoxicity risk predictors are critical to optimize cancer therapy delivery and enable early interventions to prevent progressive LVSD. While dexrazoxane-based cardioprotection reduces short-term cardiotoxicity without compromising cancer survival, liposomal anthracycline formulations have the potential to mitigate cardiotoxicity while improving antitumor efficacy. This overview summarizes the rationale and methodology of cardiac substudies within AAML1831, a randomized Children's Oncology Group Phase 3 study of CPX-351, a liposomal formulation of daunorubicin and cytarabine, in comparison with standard daunorubicin/cytarabine with dexrazoxane in the treatment of de novo pediatric AML. Methods/design: Children (age <22 years) with newly diagnosed AML were enrolled and randomized to CPX-351-containing induction 1 and 2 (Arm A) or standard daunorubicin and dexrazoxane-containing induction (Arm B). Embedded cardiac correlative studies aim to compare the efficacy of this liposomal anthracycline formulation to dexrazoxane for primary prevention of cardiotoxicity by detailed core lab analysis of standardized echocardiograms and serial cardiac biomarkers throughout AML therapy and in follow-up. In addition, AAML1831 will assess the ability of early changes in sensitive echo indices (e.g., global longitudinal strain) and cardiac biomarkers (e.g., troponin and natriuretic peptides) to predict subsequent LVSD. Finally, AAML1831 establishes expert consensus-based strategies in cardiac monitoring and anthracycline dose modification to balance the potentially competing priorities of cardiotoxicity reduction with optimal leukemia therapy. Discussion: This study will inform diagnostic, prognostic, preventative, and treatment strategies regarding cardiotoxicity during pediatric AML therapy. Together, these measures have the potential to improve leukemia-free and overall survival and long-term cardiovascular health in children with AML. Clinical trial registration: https://clinicaltrials.gov/, identifier NCT04293562. Competing Interests: KL, Jazz Pharmaceuticals (consulting, advisory board participation); KL and EC, Abbott Diagnostics (research funding). The reviewer YR declared a shared committee COG with the authors to the handling editor. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (© 2023 Leger, Robison, Narayan, Smith, Tsega, Chung, Daniels, Chen, Englefield, Demissei, Lefebvre, Morrow, Dizon, Gerbing, Pabari, Getz, Aplenc, Pollard, Chow, Tang, Border, Sachdeva, Alonzo, Kolb, Cooper and Ky.)
Databáze:	MEDLINE
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