Читать книгу Blood and Marrow Transplantation Long Term Management - Группа авторов - Страница 102

Introduction: Significant advancements in the supportive care and better conditioning regimens have led to improved survival in HCT recipients. Concurrently, an increase in the late complications have been observed in these groups compared to controls. Late effects affect almost every organ and lead to both morbidity and mortality in the HCT survivors.

Risk factors of the effects: Both clinical and genetic risk factors play a role in the development of late effects in HCT survivors. Among clinical risk factors, receipt of irradiation, certain chemotherapies (e.g. cyclophosphamide) and lifestyle factors (e.g. smoking, alcohol intake), significantly increase the risk of both cardiovascular complications and subsequent cancers. GVHD and its associated treatments (immunosuppressants) also contribute to the risk of many late effects. Among inherited risks, a genetic predisposition to enhanced toxicity (e.g. cardiotoxicity due to anthracyclines) and inherited DNA defects leading to increases in oral carcinomas in Fanconi Anemia are some examples.

Late effects: Late effects in HCT survivors may include acute and chronic infections (including HHV6, fungal and mycobacterial infections), cutaneous complications (e.g. vitiligo, carcinomas), oral cavity complications (particularly squamous cell carcinomas), hepatic complications (including cirrhosis), GI complications (e.g. malnutrition), genital complications (vaginal stenosis, phimosis etc.), renal complications (leading to chronic kidney disease), ocular complications (e.g. retinopathies, dry eye syndrome etc.), endocrine complications (diabetes and hypothyroidism), hypogonadism, fertility loss, dental complications, musculoskeletal and bone complications (including avascular necrosis and contractures), pulmonary complications (including BOS), neurologic complications (neuropathies, strokes), psychological and social complications (including financial toxicity and PTSD), sexual dysfunction, cardiovascular complications (particularly ischemic heart disease and HTN), subsequent solid malignancies, and subsequent hematologic malignancies.

Future directions: Existence of multidisciplinary clinics for the early detection and comprehensive management of these late effects is warranted given their effect on mortality and morbidity. Prospective studies with translational elements (e.g. biomarker discovery, metabolomics, microbiome assessments, etc.) are urgently needed for these HCT survivors.