Bronchiolitis obliterans syndrome epidemiology after allogeneic hematopoietic cell transplantation

Abstract

Bronchiolitis obliterans syndrome (BOS) is a pulmonary complication of allogeneic hematopoietic cell transplantation (aHCT). Recent National Institutes of Health consensus diagnostic criteria for BOS have not been assessed in a clinical setting. Modified National Institutes of Health diagnostic consensus criteria for BOS were applied to evaluate its prevalence, risk factors, and outcomes in the modern era of aHCT. Pulmonary function tests from 1145 patients were screened to identify patients with new-onset airflow obstruction. Clinical records were reviewed to exclude pulmonary infection and other causes. The overall prevalence of BOS among all transplanted patients was 5.5%, and 14% among patients with chronic graft-versus-host disease (cGVHD). The median time from transplant to meeting spirometric criteria for BOS was 439 days (range: 274-1690). Although many previously identified risk factors were not significantly associated, lower baseline FEV(1)/FVC ratio (P = .006), non-Caucasian race (P = .014), lower circulating IgG level (P = .010), and presence of cGVHD (P < 0.001) were associated with an increase in risk, with the latter associated with a 10-fold increase in risk. Multivariate analysis indicated that BOS conferred a 1.6-fold increase in risk for mortality after diagnosis. These results suggest that the National Institutes of Health diagnostic criteria can reliably identify BOS, and that it is more prevalent than previously suggested. Spirometric monitoring of high-risk patients with cGVHD may permit earlier detection and intervention for this often-fatal disease.

Figure 1

Cumulative incidence of BOS among all transplanted patients considering death as a competing risk.

Figure 2

Figure 2A. Kaplan-Meier survival estimates of transplant-related mortality comparing BOS to non-BOS cases (p=0.002). Non-cases are denoted by a solid line, cases are shown as a dashed line. Figure 2B. Kaplan-Meier survival estimates of transplant-related mortality based on clinical recognition status among BOS cases (p=0.022). Concurrently recognized cases are denoted by a dashed line, late recognized cases with a solid line, and never recognized cases with a dotted line.