针对患有非恶性疾病 (NMD) 的儿童的造血细胞移植 (HCT) 的不断进步导致幸存者数量不断增加，而晚期发生的毒性反应仍然是一个挑战。我们调查了当代接受 NMDs HCT 的儿童和青少年队列中移植后毒性的发生率和危险因素。在这项回顾性队列研究中，我们从国际血液和骨髓移植研究中心 (CIBMTR) 数据库中提取数据分析与 HCT 治疗 21 岁或以下 NMD 的晚期效应相关的效应的时间和发生率以及风险因素。感兴趣的后期影响包括缺血性坏死、白内障、充血性心力衰竭、心肌梗塞、糖尿病、性腺功能障碍、生长激素缺乏、甲状腺功能减退、需要透析的肾衰竭以及神经系统事件（中风和癫痫）。在 HCT 后 5 年和 7 年计算每种迟发效应的累积发生率。通过 Cox 比例风险回归分析评估风险因素。主要暴露包括原发性 NMD、年龄、性别、民族和种族、保险、供体和移植物类型、肌消融调节、全身照射暴露、移植物抗宿主病 (GVHD) 和移植年份。主要结局是发生率、累积发生概率（95% CI）和器官特异性迟发效应的危险因素。2000年1月1日至2017年12月31日期间，7785名21岁或以下的患者接受了HCT。 1995 名患者不符合资格或不同意纳入。来自 171 个中心的 5790 名患者参与了分析。 5790名患者中，男性3505名（60·5%），女性2285名（39·5%）。 2106 名患者 (36·4%) 为白人，771 名患者 (13·3%) 为西班牙裔，773 名患者 (12·7%) 为黑人。 1790 名 (30·9%) 患者为非美国居民。 HCT 的中位年龄为 5·5 岁（范围 0·0-21·0）。 5790 名患者中有 1127 名（19%）有一种迟发效应，381 名（7%）有至少两种迟发效应。 HCT 后 7 年，白内障的累积发病概率为 1·9 (95% CI 1·5-2·3)，糖尿病的累积发病概率为 4·9 (4·3-5·6)，糖尿病的累积发病概率为 2·6 (2 ·1-3·1) 性腺功能障碍，3·2 (2·7-3·8) 甲状腺功能减退症，5·0 (4·4-5·7) 生长障碍，8·1 (7·4- 8·9) 肾衰竭，1·6 (1·3-2·0) 缺血性坏死，0·6 (0·4-0·8) 充血性心力衰竭，0·2 (0·1-0) ·3) 用于心肌梗塞，9·4 (8·6-10·2) 用于神经系统影响。 HCT 年龄为 10 岁或以上、不相关的供体来源、全身照射和 GVHD 被确定为长期影响的危险因素。研究结果强调了对接受移植的儿童进行多学科和终身随访的必要性和可及性NMD 的 HCT。随着越来越多的儿童接受非恶性疾病的细胞疗法治疗，移植后数据的进一步分析可以越来越多地指导治疗决策和随后的长期监测。国家癌症研究所、国家心肺和血液研究所、国家过敏研究所和传染病、卫生资源和服务管理局以及海军研究办公室。版权所有 © 2024 Elsevier Ltd。保留所有权利。

Continued advances in haematopoietic cell transplantation (HCT) for children with non-malignant diseases (NMDs) have led to a growing population of survivors in whom late occurring toxic effects remain a challenge. We investigated the incidence of and risk factors for post-transplant toxicities in a contemporary cohort of children and adolescents undergoing HCT for NMDs.In this retrospective cohort study, we extracted data from the Center for International Blood and Marrow Transplantation Research (CIBMTR) database to analyse timing and incidence of effects and risk factors associated with late effects of HCT for treatment of NMDs at age 21 years or younger. Late effects of interest were avascular necrosis, cataracts, congestive heart failure, myocardial infarction, diabetes, gonadal dysfunction, growth hormone deficiency, hypothyroidism, renal failure requiring dialysis, and neurological events (stroke and seizure). Cumulative incidence of each late effect was calculated at 5 years and 7 years after HCT. Risk factors were evaluated in Cox proportional hazards regression analyses. Main exposures were primary NMD, age, sex, ethnicity and race, insurance, donor and graft type, myoablative conditioning, total-body irradiation exposure, graft-versus-host disease (GVHD), and transplant year. Primary outcomes were rates, cumulative incidence probability (95% CI), and risk-factors for organ-specific late effects.Between Jan 1, 2000, and Dec 31, 2017, 7785 patients aged 21 years or younger underwent HCT. 1995 patients were ineligible or did not consent to be included. 5790 patients from 171 centres were included in the analysis. 3505 (60·5%) of 5790 patients were male and 2285 (39·5%) were female. 2106 (36·4%) patients were White, 771 (13·3%) were Hispanic, and 773 (12·7%) were Black. 1790 (30·9%) patients were non-USA residents. Median age at HCT was 5·5 years (range 0·0-21·0). 1127 (19%) of 5790 patients had one late effect, and 381 (7%) had at least two. At 7 years post-HCT, the cumulative incidence probability was 1·9 (95% CI 1·5-2·3) for cataracts, 4·9 (4·3-5·6) for diabetes, 2·6 (2·1-3·1) for gonadal dysfunction, 3·2 (2·7-3·8) for hypothyroidism, 5·0 (4·4-5·7) for growth disturbance, 8·1 (7·4-8·9) for renal failure, 1·6 (1·3-2·0) for avascular necrosis, 0·6 (0·4-0·8) for congestive heart failure, 0·2 (0·1-0·3) for myocardial infarction, and 9·4 (8·6-10·2) for neurological effects. Age 10 years or older at HCT, unrelated donor source, total-body irradiation, and GVHD were identified as risk factors for long-term effects.The findings highlight the need for, and access to, multidisciplinary and lifelong follow-up for children undergoing HCT for NMDs. As more children undergo treatment with cellular therapies for non-malignant conditions, further analyses of post-transplant data could increasingly guide treatment decisions and subsequent long-term surveillance.National Cancer Institute, National Heart, Lung and Blood Institute, National Institute of Allergy and Infectious Diseases, Health Resources and Services Administration, and Office of Naval Research.Copyright © 2024 Elsevier Ltd. All rights reserved.