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儿童异基因造血干细胞移植后肺功能的比较纵向分析:良性疾病与恶性疾病及早期预测因素

Comparative longitudinal analysis of pulmonary function post-pediatric Allo-HSCT: benign vs. malignant diseases and early predictors.

作者信息

Li Hongjuan, Gu Yan, Zhao Xiaowei, Ding Guoyu, Zhao Yuqi, Zhang Xiaoyue, Han Yan, Li Xue, Wang Hongmei

机构信息

Department of Pediatric Hematology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, No. 16766, Jing Shi Road, Lixia District, Jinan, 250014, Shandong, China.

出版信息

Ann Hematol. 2025 Aug 8. doi: 10.1007/s00277-025-06537-1.

Abstract

Pulmonary complications are a major cause of morbidity following pediatric allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, longitudinal pulmonary function test (PFT) trajectories and early predictors of dysfunction, particularly the interplay between underlying disease, PFTs, and graft-versus-host disease (GVHD), remain poorly understood. In this retrospective single-center study, we analyzed 233 children undergoing their first allo-HSCT with ≥ 100-day survival. Patients were categorized into benign (acquired aplastic anemia, n = 142) and malignant (leukemia/lymphoma, n = 91) groups. We assessed longitudinal PFTs over 24 months and used Kaplan-Meier and multivariate logistic regression analyses to identify early predictors (including 3-month PFT values and GVHD) for subsequent Obstructive (OVD) and Restrictive Ventilatory Disorders (RVD). Over a median follow-up of 33.1 months, the malignant group exhibited significantly slower FEV1 recovery, greater severity of RVD (P = 0.006) and diffusion impairment (P = 0.040), and higher cumulative incidences of OVD (HR = 3.34, P = 0.013) and RVD (HR = 2.16, P = 0.013). The malignant group also had significantly higher rates of acute (P < 0.001) and chronic GVHD (P < 0.001). In multivariate analysis, the strongest independent predictors for RVD were lower 3-month FVC%pred (OR = 0.85, P < 0.001) and the presence of chronic GVHD (OR = 5.97, P = 0.027). For OVD, predictors were lower 3-month MEF50%pred (OR = 0.95, P = 0.030), acute GVHD (OR = 4.24, P = 0.014), and chronic GVHD (OR = 4.20, P = 0.018). Children with malignant diseases face a higher burden of post-HSCT pulmonary dysfunction, driven by both the underlying disease/treatment intensity and a higher incidence of GVHD. Early post-transplant PFTs (FVC%pred, MEF50%pred) and the development of GVHD are powerful, independent predictors of long-term ventilatory disorders. These findings underscore the need for routine, stratified longitudinal monitoring to facilitate early risk stratification and intervention.

摘要

肺部并发症是儿童异基因造血干细胞移植(allo-HSCT)后发病的主要原因。然而,纵向肺功能测试(PFT)轨迹以及功能障碍的早期预测因素,特别是基础疾病、PFT和移植物抗宿主病(GVHD)之间的相互作用,仍知之甚少。在这项回顾性单中心研究中,我们分析了233例接受首次allo-HSCT且存活≥100天的儿童。患者被分为良性(获得性再生障碍性贫血,n = 142)和恶性(白血病/淋巴瘤,n = 91)两组。我们评估了24个月内的纵向PFT,并使用Kaplan-Meier和多变量逻辑回归分析来确定随后的阻塞性(OVD)和限制性通气障碍(RVD)的早期预测因素(包括3个月时的PFT值和GVHD)。在中位随访33.1个月期间,恶性组的FEV1恢复明显较慢,RVD严重程度更高(P = 0.006)和弥散功能障碍更严重(P = 0.040),OVD(HR = 3.34,P = 0.013)和RVD(HR = 2.16,P = 0.013)的累积发生率更高。恶性组的急性(P < 0.001)和慢性GVHD(P < 0.001)发生率也明显更高。在多变量分析中,RVD的最强独立预测因素是3个月时较低的FVC%pred(OR = 0.85,P < 0.001)和慢性GVHD的存在(OR = 5.97,P = 0.027)。对于OVD,预测因素是3个月时较低的MEF50%pred(OR = 0.95,P = 0.030)、急性GVHD(OR = 4.24,P = 0.014)和慢性GVHD(OR = 4.20,P = 0.018)。患有恶性疾病的儿童面临更高的HSCT后肺功能障碍负担,这是由基础疾病/治疗强度和更高的GVHD发生率共同驱动的。移植后早期的PFT(FVC%pred,MEF50%pred)和GVHD的发生是长期通气障碍的有力独立预测因素。这些发现强调了进行常规分层纵向监测以促进早期风险分层和干预的必要性。

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