Late Adverse Events Following Stem Cell Transplantation in Childhood Acute Lymphoblastic Leukaemia: State of the Art

Acute lymphoblastic leukaemia (ALL) survivors experience a wide spectrum of adverse events occurring years following HSCT. The incidence of late adverse events (LAEs) is related to the conditioning regimen administered and to the effects of chronic GvHD. The present chapter is meant to extensively explore the long-term sequelae of HSCT, potentially involving several target organs and systems: eyes, cardiovascular system, lungs, kidneys, endocrine system, skin, and bone. Ocular LAEs encompass cataracts, dry eye syndrome, and ischaemic retinopathy, potentially arising as a result of radiation, corticosteroids, and GvHD. ALL survivors are also susceptible to increased risk of heart failure, arrhythmias, and atherosclerosis, due to the cumulative burden of cardiotoxic medications. Pulmonary LAEs include bronchiolitis obliterans, bronchiolitis obliterans organizing pneumonia, and lung fibrosis, triggered by chronic GvHD, radiation, and busulfan. Nephrotoxic medications, GvHD, and hypertension may contribute to the development of chronic kidney disease. With regard to skin and oral LAEs, chronic GvHD may result in poikiloderma, lichen planus, and xerostomia. The endocrine system is extensively affected, with survivors experiencing a variable combination of faltering growth, hypothyroidism, hypogonadism, osteoporosis, and impaired blood glucose homeostasis. In addition, osteonecrosis affects the quality of life of a remarkable share of transplanted ALL survivors. Finally, patients exhibit an increased risk of developing secondary malignancies, including skin and thyroid cancer, glioblastomas and acute myelogenous leukaemia, as a consequence of the long-standing genotoxic effects of radiation and alkylating agents. Systematic post-HSCT monitoring is crucial to mitigate the impact of LAEs on the long-term health and quality of life for childhood ALL survivors.