Abstract
Long-term survivors of acute lymphoblastic leukemia (ALL), the most common childhood malignancy, are at remarkably increased risk of heart failure (HF) in middle age, most likely due anthracycline cardiotoxicity. The role of cranial radiation therapy (CRT) in the development of left ventricular (LV) dysfunction, a predecessor of overt HF, remains unclear. Our aim was to compare LV function and systemic arterial properties according to past CRT in young adult survivors of anthracycline-treated ALL. We studied young adult survivors of childhood ALL at a median of 16 years from diagnosis treated with anthracycline-based chemotherapy, with (n = 12) or without (n = 30) CRT. In addition to fractional shortening (FS) and ejection fraction (EF), LV function was quantified by tissue Doppler imaging of the mitral annulus. Aortic strain/distensibility and arterial compliance were derived from echocardiography and simultaneously recorded pulse pressure. Despite similar FS and EF, peak mitral annular systolic velocity (median (interquartile range): 9.0 (7.5–10.0) vs. 10.0 (8.8–11.5) cm/s, p = 0.05), and early diastolic velocity (13.8 (13.0–14.8) vs. 15.5 (14.0–17.3), p = 0.01) were decreased after chemotherapy combined with CRT compared to chemotherapy without CRT. Systemic arterial compliance was lower in post-CRT subjects (1.0 (0.8–1.2 vs. 1.4 (1.1–1.7) mL/mmHg, p = 0.002). Aortic strain and distensibility were similar regardless of prior CRT. In conclusion, lower arterial compliance and subclinical LV dysfunction may be possible late consequences of past CRT in adult survivors of childhood ALL. Whether arterial stiffening is associated with future HF development in CRT-exposed ALL survivors remains to be investigated.
Highlights
Adult long-term survivors of childhood acute lymphoblastic leukemia (ALL), the most common childhood malignancy, are at risk of chronic health conditions, including atherosclerotic cardiovascular disease and heart failure (HF) [1,2,3]
The risk of developing symptomatic HF by age 40 years was elevated by 60–80%, even in low-risk subjects, from the Childhood Cancer Survivor Study (CCSS) in comparison with sibling controls, with a further increase in the mean relative risk exceeding 10 in higher-risk patients, identified on the basis of recognized risk factors for late HF [3]
The use of cranial radiation therapy (CRT) has considerably decreased over time, there are still many ALL survivors who have received prophylactic CRT based on the previous treatment protocols
Summary
Adult long-term survivors of childhood acute lymphoblastic leukemia (ALL), the most common childhood malignancy, are at risk of chronic health conditions, including atherosclerotic cardiovascular disease and heart failure (HF) [1,2,3]. In another study cohort (DCOG-LATER study, Dutch Childhood Oncology Group–Long-Term Effects After Childhood Cancer), effects of earlier disease onset, increasing anthracycline dose, and cardiac irradiation were confirmed, with the cumulative incidence of developing severe HF 40 years after cancer diagnosis averaging 10.5% in the patients who had received only cardiotoxic chemotherapy (anthracycline, mitoxantrone, or cyclophosphamide), 27.8% for those with a history of both cardiotoxic chemotherapy and radiotherapy involving the heart, and only 0.3% in survivors without any past cardiotoxic treatment [4]. Increased aortic pulse wave velocity and depressed systemic arterial compliance were previously demonstrated both early—already at 4-months after initiation of treatment with an anthracycline for various malignancies [23]—and late [24,25,26] in adolescent and young pediatric cancer survivors
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