Cardiotoxicity in pediatric lymphoma survivors

ABSTRACT

Introduction

Over the past five decades, the diagnosis and management of children with various malignancies have improved tremendously. As a result, an increasing number of children are long-term cancer survivors. With improved survival, however, has come an increased risk of treatment-related cardiovascular complications that can appear decades later.

Areas Covered

This review discusses the pathophysiology, epidemiology and effects of treatment-related cardiovascular complications from anthracyclines and radiotherapy in pediatric lymphoma survivors. There is a paucity of evidence-based recommendations for screening for and treatment of cancer therapy-induced cardiovascular complications. We discuss current preventive measures and strategies for their treatment.

Expert Opinion

Significant cardiac adverse effects occur due to radiation and chemotherapy received by patients treated for lymphoma. Higher lifetime cumulative doses, female sex, longer follow-up, younger age, and preexisting cardiovascular disease are associated with a higher incidence of cardiotoxicity. With deeper understanding of the mechanisms of these adverse cardiac effects and identification of driver mutations causing these effects, personalized cancer therapy to limit cardiotoxic effects while ensuring an adequate anti-neoplastic effect would be ideal. In the meantime, expanding the use of cardioprotective agents with the best evidence such as dexrazoxane should be encouraged and further studied.

KEYWORDS:

• Cardiotoxicity
• survivorship
• chemotherapy
• radiotherapy

Article highlights

• There is significantly improved survival of pediatric lymphoma patients making it important to focus on long-term side-effects of the treatment they received like cardiotoxicity. Pediatric lymphoma patients are especially susceptible to cardiotoxicity due to both anthracyclines and radiation therapy they receive.

• Cardiotoxicity due to anthracyclines can be cause by various pathways resulting in acute and/or long-term cardiac damage that may be permanent.

• Cardiovascular monitoring is essential for these survivors, although currently no validated evidence-based guidelines exist.

• Currently, no evidence-based treatments exist for the management of anthracycline-associated cardiotoxicity. Thus, it is important to focus on the primary prevention of cardiotoxicity with dexrazoxane for children receiving anthracyclines.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This work has been supported in part by grants from the National Institutes of Health (HL072705, HL078522, HL053392, CA127642, CA068484, HD052104, AI50274, HD052102, HL087708, HL079233, HL004537, HL087000, HL007188, HL094100, HL095127, HD80002, HD028820), Pfizer, Roche Diagnostics, the Children’s Cardiomyopathy Foundation, Sofia’s Hope, Inc., the Kyle John Rymiszewski Foundation, the Children’s Hospital of Michigan Foundation, the Scott Howard Fund, and the Michael Garil Fund.