Late-Onset, Noninfectious Pulmonary Complications following Allogeneic Hematopoietic Stem Cell Transplantation: A Nationwide Cohort Study of Long-Term Survivors

Abstract

Background: Survivors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) are at risk for pulmonary adverse events. Data on late-onset noninfectious pulmonary complications in long-term adult survivors of allo-HSCT are limited and incomplete.

Objectives: This study aimed (1) to determine occurrence and degree of pulmonary sequelae in adult survivors of allo-HSCT and (2) to identify associations between pulmonary function, high-resolution CT (HRCT), and clinical characteristics.

Method: In a nationwide, single-center cross-sectional study, 103 survivors (aged median [range] 35 [17-58] years, 53% females) were examined 17 (6-32) years after allo-HSCT and compared with healthy controls (n = 105). Methods included pulmonary function tests and HRCT.

Results: Chronic graft-versus-host disease was diagnosed in 33% of survivors, including 12% with bronchiolitis obliterans syndrome (BOS). Mean lung volumes (TLC, FVC, and FEV1) and gas diffusing capacity were >80% of predicted for the survivors as a group, but significantly lower than in healthy controls. Pathological HRCT findings were detected in 48% of the survivors (71% airways disease, 35% interstitial lung disease, and 24% apical subpleural interstitial thickening). Air trapping (%) on HRCT correlated with % predicted FEV1, p < 0.001. In a multiple logistic regression model, both BOS and pathological findings on HRCT were associated with chemotherapy prior to allo-HSCT, p < 0.05.

Conclusions: Long-term allo-HSCT survivors had significantly lower pulmonary function than age- and gender-matched healthy controls and nearly half had pathological findings on HRCT. Longitudinal data will determine if pulmonary sequelae will remain stable or progress. We recommend lifelong monitoring of pulmonary function in allo-HSCT survivors. HRCT provides additional information, but is not suited for surveillance.

Keywords: Allogeneic hematopoietic stem cell transplantation; Bronchiolitis obliterans syndrome; High-resolution CT; Long-term follow-up; Pulmonary function.