Clinical impact of airflow obstruction after allogeneic hematopoietic stem cell transplantation

Abstract

Criteria for airflow obstruction (AFO) at one year after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in pulmonary function tests (PFTs) are more stringent than the bronchiolitis obliterans syndrome (BOS) criteria of the National Institutes of Health. This single-center, retrospective cohort study evaluated the clinical impact of the AFO criteria at any time after transplantation. In 132 patients who underwent allo-HSCT from 2006 to 2016, the 2-year cumulative incidence of AFO was 35.0%, and the median time to diagnosis of AFO was 101 days after transplantation (range 35-716 days). Overall chronic graft-versus-host disease (cGVHD) incidence was significantly higher in patients with AFO than in those without AFO (80.4% vs. 47.7%, P < 0.01); notably, 37.0% of patients with AFO developed cGVHD after AFO diagnosis. AFO patients developed BOS with a 5-year cumulative incidence of 49.1% after AFO onset. The 5-year cumulative incidence of non-relapse mortality in the AFO group was higher than that in the non-AFO group (24.7% vs. 7.1%, P < 0.01). These results suggest that closely monitoring PFTs within two years after allo-HSCT, regardless of cGVHD status, is important for early detection of AFO and prevention of progression to BOS. (192words).

Keywords: Airflow obstruction (AFO); Allogeneic hematopoietic stem cell transplantation; Bronchiolitis obliterans syndrome; Chronic graft-versus-host disease.

Fig. 1

Cumulative incidence of AFO and BOS. A A 2-year cumulative incidence of AFO in all the patients was 35.0%, and the median AFO onset was 101 days (range 35–716 days) after transplantation. B A cumulative incidence of BOS from landmark days in the AFO and the non-AFO groups. In patients with AFO, the post-transplant day of AFO development is defined as the landmark day; in patients without AFO, the landmark day is defined as 101 days after transplantation, the median day of AFO onset in patients with AFO

Fig. 2

Changes in the results of pulmonary function tests (PFTs) in the AFO and the non-AFO groups. A Vital capacity as a percent of predicted (%VC), B predicted forced expiratory volume in one second (pFEV₁), C forced expiratory volume in 1 s per forced vital capacity (FEV₁/FFC) ratio at the pre-transplant, three months after transplantation, and one year after transplantation in the AFO and the non-AFO groups. Results are shown as means ± SD. A In the AFO group, the mean %VC at the pre-transplant, the three months after transplantation, and the one year after transplantation was 95.7 ± 13.4%, 86.3 ± 16.6%, and 85.2 ± 16.6%, respectively. B In the AFO group, mean pFEV₁ at the pre-transplant, the three months after transplantation, and the one year after transplantation was 91.9 ± 16.4%, 79.6 ± 19.1%, and 75.1 ± 21.6%, respectively. C In the AFO group, the mean FEV₁/FVC ratio at the pre-transplant, the three months after transplantation, and the one year after transplantation was 79.5 ± 7.8%, 75.2 ± 8.3%, and 72.1 ± 13.7%, respectively. The data were shown in only analyzed patients whose information at all 3 points was available (n = 98). The number of patients at the pre-transplant, the three months after transplantation, and the one year after transplantation was 132, 132, and 98, respectively, and analyses using a linear mixed-effects model were performed to exclude the impact of patients with missing data and did not change the results

Fig. 3

Distribution of time to onset of chronic GVHD in AFO patients. Twenty of 46 patients in the AFO group (43.5%) developed chronic GVHD preceding AFO diagnosis, whereas 17 patients in the AFO group (37.0%) had AFO diagnosis preceding chronic GVHD and the median time to develop chronic GVHD from AFO diagnosis was 41 days (range 1–181 days) in 17 patients

Fig. 4

Overall survival (OS), relapse, and non-relapse mortality (NRM) in the AFO and the non-AFO groups. A OS from landmark day. In patients with AFO, the post-transplant day of AFO development is defined as the landmark day; in patients without AFO, the landmark day is defined as 101 days after transplantation, the median day of AFO onset in the AFO group. B Cumulative incidence of relapse from landmark day. (C) Cumulative incidence of NRM from landmark day