Childhood leukemia survivors left with hearts too small for their bodies decades after doxorubicin

Adult survivors of high-risk childhood acute lymphoblastic leukemia (ALL) treated with anthracycline-based chemotherapy show a late cardiac transformation in which the left ventricle becomes progressively too small for the patient’s body size, a pattern the researchers call Grinch Syndrome. The study, published in Cardio-Oncology, reviewed the very long-term echocardiograms and cardiac status of 115 patients treated on Dana-Farber Cancer Institute Childhood ALL Consortium Protocols between 1972 and 1989, with median cardiac follow-up of 17.3 years and a range extending to 39.2 years.

The echocardiographic findings trace a shift in the nature of anthracycline-associated cardiotoxicity over time. Mean left ventricular fractional shortening, a measure of pumping function, was reduced by last follow-up, falling 2.42 standard deviations in patients followed more than 24 years. The left ventricular end-diastolic dimension followed a distinctive trajectory: it was initially dilated, subsequently normalized, and then was markedly decreased at last follow-up, a change over time that was highly significant. Reduced LV end-diastolic dimension, fractional shortening, and wall thickness were each associated with the cumulative anthracycline dose the patients received.

The ratio of ventricular wall thickness to chamber dimension also changed in a revealing way. It was significantly reduced until about 21 years of follow-up, then rose—not because the walls thickened abnormally, but because the chamber dimension shrank while wall thickness increased. Critically, this rise in wall thickness was accompanied by a progressive, significant reduction in left ventricular mass. The authors conclude that anthracycline cardiotoxicity transitions from a subclinical dilated cardiomyopathy to a restrictive-like cardiomyopathy detectable at 15 or more years after exposure, with the later phase driven more by the fall in chamber dimension below the normal range for body size than by change in wall thickness, ultimately normalizing the thickness-to-dimension ratio.

The practical consequence is that survivors are left with a heart that is functionally inadequate for their body size, even decades after treatment ended. Because cardiovascular disease is a major cause of morbidity and mortality in childhood cancer survivors, and because this restrictive-like phase emerges only after many years, the researchers emphasize that monitoring for late, clinically significant cardiotoxicity is essential in this population.

Subject of Research: Long-term anthracycline cardiotoxicity in adult survivors of childhood acute lymphoblastic leukemia

Article Title: Hearts too small for body size after doxorubicin for childhood acute lymphoblastic leukemia: Grinch Syndrome

Article References: Lipshultz, S. E., Scully, R. E., Stevenson, K. E., Flamand, Y., Colan, S. D., Vrooman, L. M., Bansal, N., & Sallan, S. E. (2026). Hearts too small for body size after doxorubicin for childhood acute lymphoblastic leukemia: Grinch Syndrome. Cardio-Oncology. https://doi.org/10.1186/s40959-026-00573-0

Image Credits: AI Generated

DOI: 10.1186/s40959-026-00573-0

Keywords: doxorubicin, anthracycline cardiotoxicity, childhood ALL, Grinch Syndrome, echocardiography, restrictive cardiomyopathy, left ventricular mass, late effects, cardio-oncology, Dana-Farber, Hearts, small