Pulmonary Complications in Patients with Primary Immunodeficiency Undergoing Hematopoietic Stem Cell Transplantation

Abstract

<h3>Introduction</h3> 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. <h3>Objectives</h3> 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. <h3>Methods</h3> 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. <h3>Results</h3> 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). <h3>Conclusion</h3> 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.