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Life sciences · Journal article
Cardio-oncology · September 28, 2026
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Cardiovascular disease is a major cause of morbidity and mortality in childhood cancer survivors. We assessed the very long-term cardiac structure and function of adult survivors of childhood leukemia treated with anthracycline-based therapy. One hundred fifteen patients with high-risk acute lymphoblastic leukemia (ALL) treated on Dana-Farber Cancer Institute Childhood ALL Consortium Protocols between 1972 and 1989 were evaluated for this study. Patient medical records were reviewed to evaluate echocardiograms and cardiac status. Median cardiac follow-up was 17.3 years (range 2.8–39.2). Mean left ventricular fractional shortening (LVFS) was reduced by last follow-up (> 24 years: -2.42 SD [ P <0.05]). Left ventricular (LV) end-diastolic dimension, initially dilated, subsequently normalized, and then was markedly decreased at last follow-up (change over time: P < 0.001). LV thickness-dimension ratio significantly reduced until 21 years of follow-up, subsequently increased secondary to a reduction in LV dimension and increasing LV wall-thickness. This rise in LV wall-thickness was accompanied by a progressive, significant reduction in LV mass. Reduced LV end-diastolic dimension, LVFS and LV wall-thickness were associated with cumulative anthracycline dose ( P <0.05). Anthracycline-associated cardiotoxicity transitions over time from a subclinical dilated cardiomyopathy to a restrictive-like cardiomyopathy detectable at ≥ 15 years after exposure. The restrictive-like phase is characterized by a progressive fall in LV dimension over time further below the normal range for body size and is more than change in LV wall-thickness, resulting in normalization of the LV thickness-to-dimension ratio. Patients are left with a heart that is functionally inadequate for their body size, or Grinch Syndrome. Monitoring for late clinically significant cardiotoxicity is essential.