# The Effect of Smoking and Pre-Allogeneic Hematopoietic Cell Transplant Pulmonary Comorbidity on the Incidence of Lung Graft-Versus-Host Disease and Post-Transplant Outcomes

## TL;DR

Smoking and lung issues before a transplant increase risks of lung GVHD and poor survival after allogeneic hematopoietic cell transplantation.

## Contribution

This study identifies a synergistic negative effect of smoking and pre-transplant pulmonary comorbidities on lung GVHD and survival outcomes.

## Key findings

- Smokers with pre-transplant lung issues had higher chronic lung GVHD and worse survival.
- Higher pack-years and recent smoking were linked to worse post-transplant outcomes.
- Non-smokers without lung issues had the best survival and lowest non-relapse mortality.

## Abstract

Smoking is linked to an increased risk of pulmonary complications and adverse outcomes following allogeneic hematopoietic cell transplantation (Allo-HCT). We retrospectively analyzed 407 patients who underwent Allo-HCT between January 2019 and May 2021 and evaluated the impact of smoking history and pre-transplant pulmonary comorbidities on post-transplant outcomes. Patients were divided into four groups: Group A: smokers with pre-transplant pulmonary comorbidity; Group B: non-smokers with pre-transplant pulmonary comorbidity; Group C: smokers without pre-transplant pulmonary comorbidity; and Group D: non-smokers without pre-transplant pulmonary comorbidity. Smokers were also grouped by their smoking history in pack-years and smoking recency. Group A showed the worst outcomes in terms of chronic lung graft-versus-host disease (GVHD), overall survival, and non-relapse mortality. Similarly, smoking recency and higher pack-years were also associated with worse outcomes. Our results showed the negative synergistic effect of smoking history and pulmonary comorbidity on the incidence of lung GVHD and survival.

Background/Objectives: Smoking is linked to an increased risk of pulmonary complications and adverse outcomes following allogeneic hematopoietic cell transplantation (Allo-HCT). Unfortunately, data is rarely correlated with the incidence of GVHD and does not show whether smoking has a negative impact independent from underlying pulmonary comorbidities. Methods: We retrospectively analyzed 407 patients who underwent Allo-HCT between January 2019 and May 2021 and evaluated the impact of smoking history and pre-transplant pulmonary comorbidities on the risk of outcomes including graft-versus-host disease (GVHD), overall survival (OS), and non-relapse mortality (NRM). Results: Patients were divided into the following groups: Group A: smokers with pre-transplant pulmonary comorbidity, 40 pts (9.8%); Group B: non-smokers with pre-transplant pulmonary comorbidity, 71 pts (17.4%); Group C: smokers without pre-transplant pulmonary comorbidity, 105 pts (25.8%); and Group D: non-smokers without pre-transplant pulmonary comorbidity, 191 pts (46.9%). Smokers were also grouped by their smoking history (<10 pack-years (59 pts), 11 to 25 pack-years (50 pts), and >25 pack-years (35 pts)) and by smoking recency: Recent (until Allo-HCT), Former (quit > 1 year ago), and Remote smokers (quit > 10 years ago). Our results showed that Group A demonstrated increased chronic lung GVHD compared to the other groups (p = 0.01). The 3-year OS was lowest in Group A at 45.0%, compared to 70.4%, 62.4%, and 69.4% (p = 0.006), and the NRM was highest at 37.5%, compared to 15.5%, 18.2%, and 14.7% in Groups B, C, and D, respectively (p = 0.001). Smoking recency and higher pack-year dose were associated with worse outcomes. Conclusions: Our study demonstrated the negative synergistic effect of smoking history and pre-transplant pulmonary comorbidities on the incidence of lung GVHD, OS, and NRM.