High Prevalence of Abnormal Baseline Lung Function in Pediatric and Young Adult Hematopoietic Stem Cell Transplant Recipients: A Report from the TRANSPIRE Study

Abstract

Background: Pulmonary complications are a major cause of morbidity and mortality in pediatric and young adult hematopoietic stem cell transplant (HSCT) recipients. The impact of preexisting lung dysfunction on posttransplant outcomes remains understudied.

Methods: In a multi-institutional prospective cohort of 444 patients (≤24 years) undergoing allogeneic HSCT at eight centers, baseline lung function was categorized as normal or abnormal using clinical history, imaging, pulmonary function tests (PFTs), and pulmonologist review. Spirometry and diffusion capacity were assessed at baseline, Day 100, 1 year, and 2 years post-HSCT.

Results: Baseline pulmonary dysfunction was present in 224 patients (50.4%), including impaired spirometry (46.4%), low diffusion capacity (33.8%), and imaging abnormalities (e.g., nodules 19%, interstitial changes 7.9%). These patients had significantly lower median z-scores for forced expiratory volume in 1 s (FEV1) (-2.3 vs. -0.5), forced vital capacity (FVC) (-2.0 vs. -0.3), and diffusion capacity of the lung for carbon monoxide (-2.4 vs. -0.7; all p < 0.001). Lung function impairments persisted through 2 years post-HSCT. FEV1 and FVC remained significantly lower at all time points; FEV1/FVC ratios were similar. Overall survival was lower in the abnormal group (88.4 vs. 95.9%). Seven respiratory-related deaths occurred, including acute respiratory distress syndrome (n = 3), respiratory failure (n = 2), diffuse alveolar hemorrhage (n = 1), and fibrotic lung disease (n = 1).

Conclusions: Pretransplant pulmonary dysfunction is common and predicts sustained posttransplant impairment and lower survival. Comprehensive baseline assessment may aid in risk stratification and guide early interventions to improve long-term respiratory outcomes in pediatric and young adult HSCT patients.

Gov identifier: NCT04098445.

Keywords: PFT; allogeneic stem cell transplant; pediatric; pulmonary dysfunction.

FIGURE 1 |

Etiologies of abnormal baseline pulmonary status. The Venn diagram shown in the top panel describes the major categories of etiologies of abnormal pulmonary function. Pulmonary function data are represented both by individual test modality (table) and by patient. The major categories include clinical history (blue), pulmonary function evaluation (yellow), chest imaging findings (red), and bronchoscopy/bronchoalveolar lavage findings (green). Each category was not mutually exclusive. Each associated bar graph demonstrates the frequency of patients each reason was chosen.

FIGURE 2 |

Longitudinal pulmonary function testing changes in abnormal and normal groups. z-Scores for (A) FEV1, (B) FVC, and (C) FEV1/FVC ratio are shown at baseline, Day 100, 1 year, and 2 years post-HSCT for patients stratified by baseline pulmonary function: abnormal (gray line) vs. normal (orange line). Error bars represent standard deviations. Patients with abnormal baseline pulmonary function had significantly lower FEV1 and FVC values at each follow-up time point compared with those with normal baseline function (p < 0.05 at all time points). No statistically significant differences were observed in FEV1/FVC ratio between groups over time. Statistical comparisons were performed using linear mixed-effects models accounting for repeated measures.