Tobacco Use Influences Disease Outcome and AML Potential in Myelodysplastic Syndromes,
Authors: Komrokji Rami S. , Rollison Dana E , Al Ali Najla H , Corrales-Yepez Maria , Epling-Burnette Pearlie K , Lancet Jeffrey E. , List Alan F. 
Published: October 2019

Abstract
Abstract 3790

Background:
Several epidemiologic studies suggest a linkage between smoking history and risk of myelodysplastic syndromes (MDS). Only one study addressed the potential impact of cigarette smoking on survival in lower risk MDS. We investigated the effect of smoking on disease outcome among MDS patients treated at the Moffitt Cancer Center (MCC).

Methods:
MDS patients were identified through the MCC database, followed by individual chart review. Tobacco use was obtained through patient self reported questionnaire. Chi square test and t-test were used to compare baseline characteristics. Kaplan Meier estimates were used to calculate overall survival (OS); log rank test was used for comparison between the different groups and Cox regression analysis was used for multivariable analysis. All analyses were conducted using SPSS version 19.0 software.

Results:
We identified 743 MDS patients evaluated at MCC with known tobacco smoking history (Data on tobacco use was only missing in 24 patients in the MDS database). Two hundred and fifty six patients never smoked (never-smoker group) and 487 patients were current or former smokers (ever smoker group). Tobacco use included current cigarettes smokers (n=70), former tobacco use (n=399), Cigar/pipe (n=16), Snuff/chew (n=2). The baseline characteristics compared between the 2 groups included age, WHO subtype, International Prognostic system (IPSS), MD Anderson risk model, karyotype, RBC transfusion dependence (RBC TD), serum ferritin, and treatment with hypomethylating agents. No statistically significant differences were observed between the 2 groups. (Table-1) In low and int-1 risk IPSS, a significantly greater proportion of poor risk karyotypes was observed in ever smokers (8.8%) versus never smokers (2.4%) (p=0.003).
With a median duration of follow up of 55 months (95%CI 50.5–59.6), median OS for never smokers was 48 months (95%CI=36.9–59.1) compared to 35 months (95%CI =28.7–41.3) in ever smokers (p=0.01). The adverse effect of smoking was greatest in low and intermediate-1 IPSS risk groups where median OS was 69 months (95%CI= 42–96) in never smokers compared to 48 months (95%CI= 41–55) in smokers (p=0.006). The median OS was 69 mo (95%CI =42–96), 50 mo (95%CI= 43–57), and 38 mo (95%CI= 23–53) respectively in never-smoker, former-smoker, and current smoker groups in lower risk MDS (p=0.01). No difference was observed in int-2 and high risk IPSS groups with a median OS of 22 months (95%CI =11.75–32.2) in never smokers and 18 months (95%CI =14.3–21.7) in the ever smoker group. (p=0.89). An adverse impact of smoking was observed in good and intermediate risk karyotypes but not in poor risk karyotypes. Among low/int-1 risk IPSS, the rate of AML transformation was 18.2% in ever smokers compared to 9.5% in non-smokers (p=0.04) while no difference in rate of AML transformation was observed in int-2/high risk IPSS MDS between the 2 groups.
In Cox regression analysis tobacco use in lower risk MDS predicted inferior OS (Hazard ratio (HR) 1.52 (95%CI 1.06–2.2) after adjustment for age >60, MD Anderson risk group, serum ferritin, RBC-TD, and use of hypomethylating agents.

Conclusions:
Our study confirms a negative impact of tobacco use on disease natural history and OS in a large cohort of MDS patients. The higher frequency of poor risk karyotype and AML progression among smoking, lower risk patients suggests that tobacco exposure influences disease biologic potential and behavioral modification to discontinue tobacco use may improve outcome.

Disclosures:
No relevant conflicts of interest to declare.