The Impact of Cigarette Smoking On Overall Survival in Non-Hodgkin Lymphoma

Smoking has been suggested as a potential risk factor for the development of non-Hodgkin lymphoma (NHL). However, the prognostic impact of smoking in patients with NHL has not been well studied and may have important implications regarding outcome.

In a population-based cohort of 308 NHL patients diagnosed between 1999 and 2002, we examined the association between cigarette smoking habits prior to NHL diagnosis and overall survival (OS). Multivariable Cox proportional hazards models adjusted for age, gender, and education were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for all NHL, and for follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL). Measurements of smoking included categories for smoking status, pack-years of smoking, years of smoking, daily number of cigarettes smoked, and years since quitting smoking. Continuous exposures for cigarette smoking were also examined with potential non-linear relations tested using restricted cubic splines. We conducted subgroup analyses adjusting for established clinical and prognostic variables.

In the patient cohort, a total of 96 deaths occurred over a median follow-up period of 8. 2 years. For all NHL cases, current smokers had worse survival (HR=1. 8 [1. 0–3. 1], p_trend=0. 07, for risk of all-cause mortality) when compared to never smokers. The inferior survival was also associated with pack-years of smoking (HR=1. 5 [0. 9–2. 4], p_trend=0. 12, for >30 pack-years) and smoking duration (HR=1. 5 [0. 9–2. 3], p_trend=0. 13, for >30 years). Smoking remained an independent predictor of OS after adjustment for initial treatment, stage at diagnosis and the presence of B symptoms: HR=2. 6 [1. 1–6. 3], p_trend=0. 03, for current smokers; HR=2. 4 [1. 1–5. 6], p_trend=0. 03, for patients with >30 pack-years of cigarette smoking; and HR=2. 5 [1. 2–5. 5], p_trend=0. 02, for patients smoking longer than 30 years. Among former smokers, a shorter interval from quitting to diagnosis was associated with worse survival (per 5 years of quitting cigarette smoking, HR=0. 9 [0. 8–1. 0], p_trend=0. 06). The associations with cigarette smoking and OS were stronger for FL than for DLBCL. In analyses stratified by age at diagnosis, the associations for current smokers (HR=3. 7 [1. 5–9. 2], p_trend=0. 01), daily number of cigarettes smoked (HR=2. 8 [1. 0–7. 5], p_trend=0. 04), and years of cigarette smoking (HR=3. 0 [1. 1–8. 3], p_trend=0. 04) were stronger for patients diagnosed at <60 years of age. The risk estimates for smoking with OS did not depart from unity among those diagnosed at ≥ 60 years of age. The associations between cigarette smoking and OS were similar for men and women.

Our data suggest that cigarette smoking prior to diagnosis is associated with inferior OS in NHL patients. The reduction in survival is most prominent for patients diagnosed at <60 years of age and for those with FL. Among former smokers, greater time from cessation of smoking to diagnosis may improve OS. Further research examining the impact of smoking cession on OS among NHL patients is warranted.

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Overall survival by smoking status among NHL patients diagnosed at <60 years of age

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Overall survival by smoking status among NHL patients diagnosed at <60 years of age

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Overall survival by smoking status among NHL patients diagnosed at ≥60 years of age

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Overall survival by smoking status among NHL patients diagnosed at ≥60 years of age

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No relevant conflicts of interest to declare.