S290: development and validation of a prognostic model of bronchiolitis obliterans syndrome in adult patients following allogeneic hematopoietic stem cell transplantation

Topic: 22. Stem cell transplantation - Clinical Background: Bronchiolitis obliterans syndrome (BOS) is a common and potentially devastating non-infectious pulmonary complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT). Although BOS is rare, affecting only 5% to 12% of HSCT recipients, it is a significant problem after HSCT because of the high attributed morbidity and mortality. Early treatment, before structural and irreversible changes have occurred, is crucial to reduce disease morbidity and mortality. Although some advances have occurred in the past decade regarding understanding its pathogenesis, information on markers for early prognostication remains limited, and no predictive tools for BOS are available. Aims: We aimed to develop and validate a prognostic model for BOS in patients who undergo allogeneic hematopoietic stem cell transplantation. Methods: We retrospectively identified a consecutive cohort comprised of 150 BOS patients from 6100 consecutive patients allografted between 2007 and 2020. The entire cohort was separated into a derivation cohort and a validation cohort, according to the time of transplantation, to perform external temporal validation. The outcome of interest was 6-month mortality. We assessed 25 widely available clinical parameters (demographic, transplant, clinical, and laboratory factors) as candidate predictors and used multivariable logistic regression to develop our prediction model. A scoring system to predict the prognosis of BOS after allo-HSCT was also established, and scores were assigned to the prognostic factors based on the regression coefficient. Results: The derivation cohort included 90 patients with BOS who received allo-HSCT from 2007 to 2017. For the external validation cohort, we included 60 patients with BOS who received allo-HSCT from 2018 to 2020. Fifty-four patients (36%) died within 6 months of their BOS diagnosis. In total, 25 candidate predictor variables were collected upon BOS diagnosis. Using multivariable logistic regression methods, declining forced expiratory volume at 1 second (FEV1) to <50% predicted (OR, 2.823; 95% CI, 1.495-4.530), patient age (OR 2.381; 95% CI, 1.312-4.238), cGVHD (OR, 2.176; 95% CI, 1.492-5.189), and hypoxemia (OR, 2.376; 95% CI, 1.351-5.013) were identified as independent prognostic factors for the 6-month outcome of BOS. A risk score model termed FACH (FEV1, age, cGVHD, hypoxemia) was constructed according to the regression coefficients. The patients were stratified into a low-risk group (0-2 points), an intermediate-risk group (3-4 points) and a high-risk group (5-6 points). We also established an easy-to-use risk heat map of BOS. The FACH model had an AUC of 0.828 (95% CI 0.748-0.909) in internal validation and 0.779 (95% CI 0.720-0.914) in external validation. Calibration plots demonstrated good consistency between FACH-predicted probability and actual observation in both internal validation and external validation. Decision curve analysis demonstrated the clinical usefulness of the FACH model. Summary/Conclusion: The FACH score is the first scoring system capable of predicting the 6-month survival of patients with BOS after allo-HSCT. It showed good performance in identifying allo-HSCT patients at increased risk of 6-month mortality after BOS diagnosis. This predictive model may contribute to the early identification of high-risk patients and facilitate future studies on developing individualized and novel interventions for patients within different risk groups. Keywords: Complications, Survival prediction, Allogeneic hematopoietic stem cell transplant