Cigarette Smoking Is Associated with Increased Rates of Fungal Infection and Increased Mortality After Allogeneic Transplantation
Authors: Hill Brian T. , Bolwell Brian J. , Rybicki Lisa , Sekeres Mikkael A. , Mansour Mary , Dean Robert , Pohlman Brad , Tench Shawnda , Sobecks Ronald , Andresen Steven , Kalaycio Matt , Copelan Edward A. 
Published: October 2019

Abstract
Abstract 2321

Introduction:
Prior reports on the effect of smoking on outcomes of stem cell transplantation (SCT) have demonstrated an increased mortality for smokers but have not examined the incidence of fungal infection1-2. Tobacco cigarettes contain aspergillus spores that could serve as a source of fungal infection in immunocompromised patients after allogeneic SCT3. To determine the impact of smoking on transplant outcomes, we retrospectively analyzed data from patients undergoing allogeneic SCT at the Cleveland Clinic and compared the survival and incidence of fungal infection in patients who have smoked cigarettes with those who have never smoked.

Methods:
We identified 237 consecutive patients using the following inclusion criteria: age ≥18, and myeloablative allogeneic SCT for hematologic malignancy between 2004 and 2009. Survival was estimated using the Kaplan-Meier method and compared according to prospectively-collected smoking history. Smokers were more likely than nonsmokers to be male (59.0% vs. 45.5%, P = 0.046), caucasian (92.8% vs. 84.4%, P= 0.06) and have an unrelated donor (63.9% vs. 48.1%, P = 0.02) but were similar in terms of median age (45 vs. 46, P = 0.85) and hematopoietic stem cell transplant comorbidity index (36.1% low, 27.7% intermediate, 36.1% high vs. 39.0%, 30.5%, 30.5%, P = 0.68). In addition, we analyzed the incidence of fungal infection in 145 consecutive patients with a diagnosis of acute myeloid leukemia (AML) who underwent allogeneic SCT between 1994 and 2009. We categorized the type of fungal infection as possible, probable or proven using the Revised Infectious Diseases Society of America (IDSA) guidelines.

Results:
154 of 237 (65.0%) patients who underwent allogeneic transplant had never smoked and 83 (35%) had a history of at least some cigarette smoking. 4 year survival was 42.3% for nonsmokers and 26.4% for smokers (P = 0.004). Multivariable analysis demonstrated a hazard ratio of 1.56 for overall mortality after allogeneic transplantation for smokers (95% confidence interval 1.10 – 2.22, P = 0.013). A Kaplan-Meir survival curve for smokers and nonsmokers is shown below. Patients with AML who had a history of cigarette smoking had a higher incidence of proven or probable fungal infection after allogeneic SCT than nonsmokers (16.3 % vs. 2.9%, P < 0.001).

Conclusion:
Cigarette smoking is independently associated with increased mortality after allogeneic SCT. Although the effects of cigarette smoking are likely multifactorial, a significantly higher incidence of fungal infections may contribute to the poorer outcomes of smokers after transplantation.
References:
1. Marks, D, et al. The Effect of Smoking on Allogeneic Transplant Outcomes. BBMT. 2009;15(10), 1277–1287.
2. Ehlers, SL et al. al. The impact of smoking on outcomes among patients undergoing hematopoietic SCT for the treatment of acute leukemia. BMT, May 2010.
3. Verweij, PE, et al: Fungal contamination of tobacco and marijuana. JAMA. 2000;284(22), 2875.

Disclosures:
No relevant conflicts of interest to declare.