Introduction

Allogeneic hematopoietic stem cell transplantation (HSCT) is curative therapy for a variety of primary immunodeficiency disorders (PIDs). Patients with PID have high rates of pulmonary disease from infections and immune-mediated lung damage, and post-HSCT pulmonary complications account for considerable morbidity and mortality. It is unknown whether pre-HSCT pulmonary disease places PID patients at higher risk for post-HSCT complications. We hypothesize that PID patients with pre-HSCT pulmonary disease have higher risk of transplant-related mortality (TRM), more pulmonary complications, and lower overall survival (OS) compared to PID patients without pre-HSCT pulmonary disease.

Objectives

The primary aim of this study is to compare TRM in PID patients with and without pre-HSCT pulmonary disease. Secondary aims of the study are to compare OS, incidence of non-infectious and infectious pulmonary disease post-HSCT, ICU transfer for any cause, incidence of acute or chronic GVHD, and immune reconstitution.

Methods

This is a single center, retrospective, chart review. All pediatric patients (ages 0-18 years) who underwent allogeneic HSCT for a diagnosis of a PID at Boston Children's Hospital from January 2007-June 2018 (n=115) were included in the analysis. We defined non-infectious pulmonary disease as either functional lung impairment based on pulmonary function tests (PFTs), radiographic evidence of pulmonary disease, or documentation of a specific pulmonary diagnosis. We defined infectious pulmonary disease as either viral, bacterial, fungal or other infection in conjunction with positive radiographic and/or bronch/BAL findings.

Results

Within our cohort, the most common PIDs were SCID (n=28), DOCK8 deficiency (n=16), Wiskott-Aldrich syndrome (n=15), and chronic granulomatous disease (n=9). Of the 115 patients, 54 (47%) had a pre-HSCT diagnosis of pulmonary disease. Pulmonary infection (n=30) and bronchiectasis (n=11) were the most common diagnoses (Fig. 1A). Compared to patients without pre-HSCT lung disease, patients with pre-HSCT lung disease had higher numbers of pulmonary complications after HSCT, such as the need for non-invasive or mechanical ventilation (23 of 54 patients [43%] vs. 12 of 61 patients [20%]) (Fig. 1B). Amongst patients with pre-HSCT lung disease, 1-year survival was 81% compared with 92% in patients without pre-HSCT lung disease. Overall survival was 76% at a median follow up time of 1.6 years versus 89% at a median follow up of 2.7 years in patients with and without pre-HSCT lung disease, respectively (censored logrank p = 0.05) (Fig. 2).

Conclusion

Within our single center study, PID patients with pre-HSCT lung disease had a trend towards more post-HSCT lung complications and lower OS compared to PID patients without pre-HSCT lung disease. Pulmonary risk factors should be carefully considered in PID patients prior to HSCT.

中文翻译：

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原发性免疫缺陷患者接受造血干细胞移植的肺部并发症。

介绍

异基因造血干细胞移植（HSCT）是治疗各种原发性免疫缺陷疾病（PID）的有效方法。PID的患者因感染和免疫介导的肺损伤而患肺病的几率很高，HSCT后的肺部并发症导致相当高的发病率和死亡率。尚不清楚HSCT之前的肺部疾病是否会将PID患者置于HSCT术后并发症的更高风险中。我们假设与没有HSCT之前的肺部疾病的PID患者相比，患有HSCT之前的肺部疾病的PID患者具有更高的移植相关死亡率（TRM），更多的肺部并发症和较低的总体生存率（OS）。

目标

这项研究的主要目的是比较有和没有HSCT前肺部疾病的PID患者的TRM。该研究的次要目的是比较OS，HSCT后非感染性和感染性肺部疾病的发生率，任何原因的ICU转移，急性或慢性GVHD的发生率以及免疫重建。

方法

这是一个单一的中心回顾性图表审查。分析包括2007年1月至2018年6月在波士顿儿童医院接受同种异体HSCT诊断为PID的所有儿科患者（0-18岁）（n = 115）。我们将非感染性肺疾病定义为基于肺功能检查（PFT）的功能性肺损伤，肺部疾病的放射学证据或特定肺部诊断的文献。我们将感染性肺部疾病定义为病毒，细菌，真菌或其他感染，并结合放射线影像学和/或支气管/ BAL阳性结果。

结果

在我们的队列中，最常见的PID是SCID（n = 28），DOCK8缺乏症（n = 16），Wiskott-Aldrich综合征（n = 15）和慢性肉芽肿病（n = 9）。在115位患者中，有54位（47％）曾在HSCT前被诊断出患有肺部疾病。肺部感染（n = 30）和支气管扩张（n = 11）是最常见的诊断（图1A）。与没有HSCT前肺部疾病的患者相比，HSCT前肺部疾病的患者发生HSCT后的肺部并发症数量更高，例如需要无创通气或机械通气（54例患者中的23例[43％]，而12例患者中的12例）。 61名患者[20％]）（图1B）。在患有HSCT之前的肺部疾病的患者中，一年生存率为81％，而没有患有HSCT之前的肺部疾病的患者为92％。中位随访时间为1.6年，总生存率为76％，而中位随访时间为2，则为89％。

结论

在我们的单中心研究中，与没有HSCT之前的肺部疾病的PID患者相比，患有HSCT之前的肺部疾病的PID患者有发生HSCT之后的肺部并发症的趋势更大，OS降低的趋势。在进行HSCT之前，PID患者应仔细考虑肺部危险因素。