Impact of Different Ex Vivo T-Cell Depletion Strategies on Outcomes Following Hematopoietic Cell Transplantation for Children with Primary Immunodeficiency (original) (raw)

2020, Biology of Blood and Marrow Transplantation

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.