Heart failure (HF) is a common severe non-malignant complication in childhood cancer survivors (CCS). We performed a systematic review to identify, critically appraise and synthesize population-based studies reporting on the incidence and/or prevalence of HF in 5-year CCS (age <18 years). A comprehensive literature search was carried out until March 14 th, 2023, yielding 3883 records, of which four were found eligible. Screening, data extraction, and quality assessment were conducted independently by two reviewers. A meta-analysis of three similar studies found a cumulative incidence of 0.99% (95% CI 0.57–1.42) over 5.0-72.5 years (I-squared=94.4%, p<0.001). Existing population-based studies reporting on HF in 5-year CCS are few and heterogeneous. Further studies are required to enable the development of effective surveillance strategies.

Background: Heart transplantation (HTx) relies on an endomyocardial biopsy for rejection surveillance. Cell-free DNA (cfDNA) is released into the circulatory system from the cells of the recipient (recipient-derived rd-cfDNA) as well as from the graft (donor-derived dd-cfDNA) and is determined by the analysis of a blood test. There is growing evidence that the donor fraction (DF, the ratio of dd-cfDNA to all cfDNA) corresponds to the integrity of the graft. However, it is important that rd-cfDNA levels vary greatly in different, sometimes clinically silent circumstances, which in turn makes DF the sole measure of graft status vulnerable to bias. Methods: Using a digital PCR-based method that allowed us to quantify separate values of rd-cfDNA, dd-cfDNA, and DF, we investigated a prospective cohort of 52 patients during their first year after HTx. Results: We found median DF levels of approximately 0.1%, which is in accordance with the literature. We present patients with various clinical scenarios after HTx, including an uncomplicated clinical course, several infections (viral and bacterial), acute and chronic rejection, and false-negative and false-positive rejections. Conclusions: Quantification of circulating cfDNA reflects a live-view of cell turnaround in the recipient and graft. Measuring the DF alone may not be sufficient to fully understand the complex biology of cfDNA after HTx.