Therapy with sirolimus in vascular anomalies: the experience of two Italian centers on 14 pediatric patients.

Introduction: Vascular anomalies (VAs) constitute a heterogeneous group of tumors and malformations capable of inducing significant clinical events in specific patients, such as the compression of vital organs, pain, functional impairment, or acquired coagulopathy. Molecular investigations into the underlying mechanisms of VAs have unveiled the frequent involvement of the PI3 K/AKT/mTOR pathway. Sirolimus, a specific mTOR inhibitor, has emerged as a potential therapeutic agent; however, its routine clinical application in complex VAs is currently restricted by a lack of extensive clinical experience. Methods: Between 2015 and 2024, we administered sirolimus to 14 pediatric patients with various types of vascular anomalies in two Italian centers, subjecting them to clinical and instrumental follow-up to investigate its efficacy and the possible occurrence of adverse events. Results: An overall improvement in or stability of their vascular anomalies was reported by 86% of patients. We also assessed toxicity, noting a low prevalence of life-threatening adverse events: only one case of sepsis was reported in a patient with a severe clinical condition, and four cases of recurrent aphthosis (28%) were reported. The most common side effect was dyslipidemia, with 43% of patients developing hypercholesterolemia (21%) or hypertriglyceridemia (21%), although these patients generally did not reach severe levels. Discussion: In line with data in the literature, according to our experience, medical therapy with sirolimus should be considered in pediatric patients affected by vascular anomalies.

Physical activity and late effects in childhood acute lymphoblastic leukemia long-term survivors.

In the present study the authors evaluated therapy-related long-term adverse effects and physical activity in a cohort of long-term survivors of childhood acute lymphoblastic leukemia (ALL), diagnosed in their center between March 1991 and August 2000, treated according to the AIEOP (Associazione Italiana di Ematologia e Oncologia Pediatrica) ALL 91 or 95 study protocol and regularly seen in the authors' long-term follow-up unit. The authors analyzed the long-term sequelae of major body systems in this cohort of subjects and administered an "ad hoc" questionnaire concerning sport. The authors found that 70 patients out of 102 (68.5%) showed no late effects, 10% presented only instrumental or neuropsychological test abnormalities, and 21.5% had 1 or more clinical late sequelae. None of the evidenced late effects represented a contraindication to do physical activity. Sixty-one percent of survivors do physical activity, most of them regularly. Sixty-one percent of males and 18.5% of females (P < .005) do competitive sport (sports rates are similar to those of the general age-matched population). Nearly all subjects spontaneously choose to do sport and think physical exercise is an important and useful resource for their health. The authors conclude that the more recent therapy regimens for leukemia treatment, excluding bone marrow transplantation, do not seem to cause such late effects as to prevent survivors from doing sport. Therefore, in the care of ALL survivors, physical activity is not only not contraindicated, but should also be promoted as much as possible. The development of specific educational programs is warranted as part of the care of cancer survivors.