A strategy to reduce cumulative anthracycline exposure in low-risk pediatric acute myeloid leukemia while maintaining favorable outcomes

Himalee S. Sabnis, Katherine A. Minson, Caitlin Monroe, Kristen Allen, Jonathan L. Metts, Todd M. Cooper, William G. Woods, Sharon M. Castellino, Frank G. Keller

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Advances in risk stratification have improved the 3-year disease-free survival (DFS) and overall survival (OS) of low-risk pediatric acute myeloid leukemia (LR-AML) to approximately 70 % and 85 % respectively. LR-AML is defined by favorable cytogenetic/molecular features and/or optimal early response to therapy. However, cumulative anthracycline exposure in contemporary Children's Oncology Group (COG) regimens approach a doxorubicin equivalent exposure of 540 mg/m2; with rates of non-infection related left ventricular systolic dysfunction (LVSD) approaching 15 %. This is a major cause of toxicity in these patients and precludes the further use of anthracyclines in the relapsed setting; therefore, strategies that reduce cardiotoxicity while maintaining excellent outcomes are needed. Patients and methods: Twenty-seven pediatric patients with LR-AML were treated with an anthracycline-reduced approach (Aflac-AML regimen) between 2011 and 2016. Patients received four courses of therapy including three high-dose cytarabine containing courses and a cumulative doxorubicin equivalent exposure of 390 mg/m2, a 28 % reduction in anthracycline dosing compared to current COG regimens. Results: The 3-year DFS and OS was 70.0 % and 85.5 % respectively, from end of Induction I (first chemotherapy cycle) with a median follow-up of 3.2 years. These survival outcomes are comparable to current LR-AML regimens. Only two patients developed non-infection related LVSD during therapy and more importantly, none developed LVSD after completion of therapy. Conclusion: These findings suggest that LR-AML outcomes can be maintained using a reduced anthracycline chemotherapy regimen, resulting in lower cardiac toxicity. This new chemotherapy backbone is now being tested prospectively (NCT04326439) to further validate its use in pediatric LR-AML.

Original languageEnglish (US)
Article number106421
JournalLeukemia Research
Volume96
DOIs
StatePublished - Sep 2020

Keywords

  • AML
  • Anthracycline
  • Cardiotoxicity
  • Low-risk
  • Pediatric

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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