Abstract 17138: Emergence of a Unique Biomarker Signature in Pediatric Patients With Developing Chemotherapy Cardiotoxicity
Background: A class of chemotherapeutics commonly used in pediatric cancer is the anthrycylines (ACs), but often is associated with left ventricular dysfunction: i.e. chemotherapy induced cardiotoxicity (CIC). The goal of this project was to examine whether a specific set of plasma biomarkers could be identified in pediatric patients undergoing initial AC treatment and at risk for CIC as well as examined in relationship to referent normal pediatric patients.
Methods and Results: AC treated pediatric patients (n=17, diagnosed with cancer (most commonly Hodgkin’s Lymphoma) with set dosing intervals and maximal AC doses of 325 mg/m2)) underwent cardiac MRI 24-48 hours after AC therapy for LV ejection fraction (LVEF) and plasma obtained at baseline (initial AC treatment) and with repeat studies (up to 12 mos). Plasma was also collected from referent normal pediatric subjects (n=66). Multiplex arrays quantified signatures from the inflammatory (8 unique cytokines) and matrix remodeling (13 unique matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs)) domains. LVEF fell from baseline with continued AC treatment (63±2 vs 57±1%, p<0.05), consistent with CIC onset. A differential inflammatory/matrix signature emerged in AC patients compared to normal (Table), including increased interleukin-8 and MMP levels. With longer periods of AC dosing, MMP-7, a marker of macrophage proteolytic activation, increased by 165±54% whereas interleukin-10, an anti-inflammatory marker, fell by 75±13% (both p<0.05).
Summary: The unique findings from this study were 2-fold. First, a differential biomarker signature containing both inflammatory and matrix domains occurs early in AC treatment. Secondly, dynamic changes in these domains occur as a function of time and progression to CIC. These findings provide potential prognostic and mechanistic insight into the natural history of pediatric chemotherapy cardiotoxicity.
Author Disclosures: O.H. Toro-Salazar: None. E. Gillan: None. M. O’Loughlin: None. J. Ferranti: None. K.N. Zellars: None. P.E. Perreault: None. K. Mason: None. B. Liang: None. S. Upadyay: None. W. Mazur: None. S. Raman: None. K. Hor: None. F.G. Spinale: Research Grant; Significant; NIH. Consultant/Advisory Board; Modest; Boston Scientific, Novartis, Amgen, Acorda.
- © 2016 by American Heart Association, Inc.