Incidence, risk factors and clinical characteristics of bronchiolitis obliterans after allogeneic hematopoietic stem cell transplantation

Bronchiolitis obliterans (BO) is a severe form of chronic graft-versus-host disease (cGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). 
Aim. The aim of current study was to evaluate the incidence, risk factors, and clinical manifestation of BO after allo-HSCT. 
Methods. The study included 1189 adult patients who received allo-HSCT at R.M.Gorbacheva Research Institute of Pediatric Oncology, Hematology and Transplantation, Academician I.P.Pavlov First Federal Saint-Petersburg State Medical University, Healthcare Ministry of Russia in 2008 – 2019. BO was diagnosed according to the US National Institutes of Health criteria (2014), including pulmonary function test (PFT) and high-resolution computed tomography (HRCT) of the chest. We analyzed the cumulative incidence of BO with competing events, risk factors in the Fine – Gray regression model, clinical symptoms, BO severity, and bronchial obstruction formation dynamics. 
Results. BO was diagnosed in 42 (3.5%) patients. Cumulative incidence of BO was 1.8% (95% CI, 1.2 – 2.7), 3.9 (95% CI, 2.8 – 5.2) и 4.5% (95% CI, 3.2 – 6.1) at 1, 3, and 5 years after allo-HSCT, respectively. The median time of BO onset and diagnosis was 321 (86 – 1 771) and 371 (161 – 2 134) days, respectively. Risk factors were HLAmismatched unrelated and haploidentical donor (ОР – 2.301, 95% CI, 1.247 – 4.246; p = 0.0076), myeloablative conditioning (ОР – 2.544, 95% CI, 1.384 – 4.674; p = 0.0026) and GVHD prophylaxis without posttransplant cyclophosphamide (ОР – 2.152, 95% CI, 1.154 – 4.013; p = 0.0160). The clinical manifestation included cough (88 %) and shortness of breath (90%). Bronchial wall thickening (95%) and expiratory air trapping (79%) were frequent chest HRCT findings. Mild, moderate, and severe BO was identified in 9 (21%), 12 (29%), and 21 (50%) patients, respectively. The median forced expiratory volume in 1 second (FEV1 ) was 39% (20 – 74). The most significant loss of bronchial conductivity was between day + 100 and 1 year after allo-HSCT. 
Conclusion. The large cohort study provided details on current incidence, risk factors, and clinical features of BO after HSCT. The results create the basis for predicting and early diagnosis of BO after allo-HSCT

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