Bone Marrow Transplantation (2015) 50, 1141–1143 © 2015 Macmillan Publishers Limited All rights reserved 0268-3369/15 www.nature.com/bmt
LETTER TO THE EDITOR
Tobacco smoking is associated with infectious pulmonary complications after allogeneic hematopoietic stem cell transplantation Bone Marrow Transplantation (2015) 50, 1141–1143; doi:10.1038/ bmt.2015.116; published online 18 May 2015 Table 1.
Although encouraging survival statistics are now reported after allogeneic hematopoietic stem cell transplantation (allo-HSCT), pulmonary complications represent major causes of morbidity and mortality.1 Smoking is known to be associated with increased risk of various diseases, and can be a risk factor for respiratory tract infection in immunocompetent patients.2 In patients with AML, smoking has been reported to increase the rate of pulmonary infections during induction chemotherapy.3 In allo-HSCT, several studies have reported the impact of smoking on transplant outcomes. Some reports have reported smoking before allo-HSCT to be correlated with poor transplant outcomes such as lower overall survival (OS),4,5 disease-free survival (DFS)4 and increased non-relapse mortality (NRM) or disease relapse.4 Conversely, other studies have shown no apparent association between smoking and mortality after HSCT.6,7 An association between smoking and post-transplant pulmonary complications has also been reported in some studies. However, these reports were limited to only severe cases, and the clinical impact of smoking on the entire spectrum of pulmonary complications remains unclear. Therefore, we retrospectively analyzed 286 patients aged ⩾ 20 years with hematological disorders who underwent their first allo-HSCT at our hospital between 2005 and 2010. We evaluated the impact of tobacco smoking before allo-HSCT on clinical outcomes, with particular focus on pulmonary complications. The tobacco consumption of each patient was evaluated by the Brinkman Index (BI).8 The BI was calculated by multiplying the number of cigarettes smoked per day by the duration of smoking (years). The study patients were classified into three smoking groups according to BI: never smokers (BI = 0, n = 126); low-dose smokers (0 oBI o 400, n = 93) and high-dose smokers (BI ⩾ 400, n = 67). For patients with ⩾ 2 pulmonary events, only the first event was analyzed. Patient characteristics are summarized in Table 1. The patients in the high-dose smokers group were older, predominantly male and received reduced-intensity regimen and tacrolimus-based GvHD prophylaxis more frequently than the patients in the other groups (Table 1). Neither forced expiratory volume in 1 s nor percent of predicted forced vital capacity values were significantly different among the three groups. The median follow-up period after HSCT was 1165 days (36–2375 days). Ninety patients eventually developed pulmonary complications at a median of 184.5 days (7–803 days) after HSCT. The cumulative incidence of pulmonary complications was 26% in the never smokers group, 36% in the low-dose smokers group and 46% in the high-dose smokers group (P = 0.02, Figure 1a). Pulmonary complications seemed to develop in a dose-dependent manner. High-dose smoking (BI ⩾ 400) was significantly associated with a higher incidence of pulmonary complications in both univariate (relative risk (RR) 2.02, 95% confidence interval (CI) 1.21–3.35, P o0.01) and multivariate analysis (RR 1.78, 95% CI 1.06–3.00, P = 0.03) (Supplementary Table 1). The BI score was also associated with
Patient characteristics Never smokers
P-valuea
Smokers Low-dose (BI, 1–399)
High-dose (BI ⩾ 400)
126 (44%)
93 (33%)
67 (23%)
Age, years Median Range
42 21–68
36 20–73
54 34–69
o0.01
Sex Male Female
41 85
69 24
61 6
o0.01
Disease riskb Low High
67 59
35 58
29 38
0.07
Stem cell source Bone marrow Peripheral blood Cord blood
98 14 14
62 17 14
53 5 9
0.26
Donor type Related Unrelated
38 88
29 64
11 56
0.07
Conditioning regimen Myeloablative TBI Non-TBI Reduced intensity
42 58 26
42 33 18
28 17 22
0.03
0.02
No. of patients
GvHD prophylaxis Cyclosporinebased Tacrolimus-based
72
54
25
54
39
42
% of predicted FEV1 ⩾ 80% o80% Unknown
118 6 2
87 5 1
60 4 3
0.94
% of predicted FVC ⩾ 80% o80% Unknown
122 2 2
89 3 1
64 0 3
0.38
Abbreviations: BI = Brinkman index; FEV1 = forced expiratory volume in 1 s; FVC = forced vital capacity. aCategorical variables were compared using the χ2-test and continuous variables were compared using the Kruskal–Wallis test. bLow-disease risk included acute leukemia in first CR, CML in first chronic phase, myelodysplasia refractory anemia, malignant lymphoma in CR and nonmalignant hematologic diseases; whereas high-disease risk included all other diagnoses.
Letter to the Editor
1142 Never smokers Low dose smokers High dose smokers
0.8 0.6 0.4 0.2
c
1.0
Never smokers Low dose smokers High dose smokers
0.8 0.6 0.4 0.2 0.0
0.0 1 2 3 4 5 6 Years after transplantation
1 2 3 4 5 6 Years after transplantation
0.8 0.6 0.4 0.2
0
1 2 3 4 5 6 Years after transplantation
e
d Cumulative incidence of relapse
Never smokers Low dose smokers High dose smokers
0.0 0
1.0
Never smokers Low dose smokers High dose smokers
0.8 0.6 0.4 0.2
1.0 Adjusted probability of disease free survival
0
1.0
Cumulative incidence of non-relapse mortality
b
1.0
Adjusted probability of overall survival
Cumulative incidence of pulmonary complication
a
Never smokers Low dose smokers High dose smokers
0.8 0.6 0.4 0.2 0.0
0.0 0
1 2 3 4 5 6 Years after transplantation
0
1 2 3 4 5 6 Years after transplantation
Figure 1. Cumulative incidence of pulmonary complications (a), adjusted probability of OS (b), NRM (c), the cumulative incidence of relapse (d), and adjusted probability of DFS (e) after allo-HSCT according to smoking dose. Adjusted probabilities of OS and DFS were compared using the Cox proportional hazards regression model. Cumulative incidences of pulmonary complications, NRM and relapse were estimated using the cumulative incidence function method and compared using Gray’s test.
pulmonary complications in both univariate (RR 1.01, 95% CI 1.00–1.01, P o0.01) and multivariate analysis (RR 1.01, 95% CI 1.00–1.01, P = 0.02), even when BI was treated as a continuous variable (Supplementary Table 1). Pneumonia was the main cause of pulmonary complications, and occurred in 17% of patients in the never smokers group, 25% in the low-dose smokers group and 33% in the high-dose smokers group (P = 0.02, Supplementary Table 2). The rates of other causes of pulmonary complications, including non-infectious complications, were almost similar among the three groups, although the number of patients was limited. In previous studies, smoking has been reported to be a significant risk factor for the development of pulmonary complications after allo-HSCT. Savani et al.9 reported that pretransplant smoking history was associated with increased NRM from pulmonary causes, most of which were idiopathic pneumonia syndrome. Similarly, Tran et al.7 reported that smoking dose was linked with an increased risk of respiratory failure within 100 days after transplantation. Conversely, Ho et al.10 showed that smoking history was not associated with increased severe pulmonary complications, defined as diffuse alveolar hemorrhage, need for mechanical ventilation, or death from respiratory failure. These differences in findings may be owing to the definition of pulmonary complications and the subject population of the studies. However, the results of the present study indicate that smoking can increase the risk, not only for life-threatening pulmonary events, but also for the entire range of posttransplant pulmonary complications, especially for pulmonary infections. Impaired mucociliary clearance, reduced phagocytosis and lower secretion of cytokines by alveolar macrophages observed in smokers may promote their susceptibility to pulmonary infections after allo-HSCT.11 In addition, microbial virulence and antibiotic resistance promoted by smoking may also Bone Marrow Transplantation (2015) 1141 – 1143
advance the development of post-transplant pulmonary infections.11 In the present study, OS adjusted for age, sex, type of conditioning regimen and GvHD prophylaxis was similar among the three groups (Figure 1b). Disease relapse/progression was the most common cause of death, and pneumonia was the second or third leading cause of death in all three groups (Supplementary Table 3). NRM at 3 years after allo-HSCT was 20%, 22% and 24% (P = 0.84, Figure 1c), and the cumulative incidence of relapse at 3 years was 29%, 25% and 35% in the never, low-dose and high-dose smokers groups, respectively (P = 0.36, Figure 1d). DFS adjusted for age, sex, conditioning regimen and GvHD prophylaxis was similar among the three groups (Figure 1e). Several studies have examined the association between cigarette smoking and post-transplant survival or relapse. In a large retrospective study of CML patients by Marks et al.,4 high-dose smoking was associated with significantly reduced OS, DFS and increased NRM. Ehlers et al.5 also reported that current smoking appeared to adversely affect OS. However, the results of the present study showed that pre-transplant high-dose smoking did not affect OS, DFS and NRM. In the study by Marks et al., all patients were conditioned by a myeloablative regimen and bone marrow transplantation was performed more frequently compared with the patients in the present study. In addition, smoking dose did not affect the post-transplant outcomes in unrelated HSCT.4 Ehlers et al.5 analyzed acute leukemia patients, including those undergoing both autologous and allogeneic transplantation; the majority of the patients were conditioned by cyclophosphamide and TBI. The present study included various hematological malignancies. Furthermore, 208 of 286 (72%) patients received HSCT from unrelated donors and 66 (23%) patients were conditioned by a reduced-intensity conditioning regimen. © 2015 Macmillan Publishers Limited
Letter to the Editor
1143 Thus, differences between patients and transplant backgrounds may affect the outcomes. With regard to disease relapse, study results have been somewhat conflicting. Smoking was associated with disease relapse in some studies6,7 but not in another study4 or in the present study. These discrepancies may also be due to differences between patients and transplant backgrounds. The present study had some limitations. First, given the retrospective nature of the study, some pulmonary complications may have been missed despite the detailed database and extensive chart review. In addition, we analyzed only the first episode if the patients had multiple pulmonary events. Thus, the incidence of late-onset pulmonary complications may have been underestimated. The second limitation is that the heterogeneous backgrounds of the patients may have biased our results, although we adjusted the factors in the multivariate analyses. The third limitation is that we could not follow the patients’ smoking status after allo-HSCT, which might influence transplant outcomes. In summary, the findings of the present study indicated that pretransplant tobacco smoking as measured by BI is an independent risk factor for the development of infectious pulmonary complications in a dose-dependent manner after allo-HSCT. Further prospective studies are warranted to confirm whether early smoking cessation would decrease the incidence of pulmonary complications after allo-HSCT. CONFLICT OF INTEREST The authors declare no conflict of interest.
ACKNOWLEDGEMENTS We are very grateful to the patients who participated in this study. We would like to thank the nursing staff at the Tokyo Metropolitan Cancer and the Infectious Diseases Center, Komagome Hospital for their excellent patient care.
R Hanajiri, K Kakihana, T Kobayashi, N Doki, H Sakamaki and K Ohashi Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan E-mail: [email protected] REFERENCES 1 Lucena CM, Torres A, Rovira M, Marcos MA, de la Bellacasa JP, Sanchez M et al. Pulmonary complications in hematopoietic SCT: a prospective study. Bone Marrow Transplant 2014; 49: 1293–1299. 2 Nuorti JP, Butler JC, Farley MM, Harrison LH, McGeer A, Kolczak MS et al. Cigarette smoking and invasive pneumococcal disease. Active Bacterial Core Surveillance Team. N Engl J Med 2000; 342: 681–689. 3 Chelghoum Y, Danaila C, Belhabri A, Charrin C, Le QH, Michallet M et al. Influence of cigarette smoking on the presentation and course of acute myeloid leukemia. Ann Oncol 2002; 13: 1621–1627. 4 Marks DI, Ballen K, Logan BR, Wang Z, Sobocinski KA, Bacigalupo A et al. The effect of smoking on allogeneic transplant outcomes. Biol Blood Marrow Transplant 2009; 15: 1277–1287. 5 Ehlers SL, Gastineau DA, Patten CA, Decker PA, Rausch SM, Cerhan JR et al. The impact of smoking on outcomes among patients undergoing hematopoietic SCT for the treatment of acute leukemia. Bone Marrow Transplant 2011; 46: 285–290. 6 Chang G, Orav EJ, McNamara T, Tong MY, Antin JH. Depression, cigarette smoking, and hematopoietic stem cell transplantation outcome. Cancer 2004; 101: 782–789. 7 Tran BT, Halperin A, Chien JW. Cigarette smoking and outcomes after allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 2011; 17: 1004–1011. 8 Brinkman GL, Coates EO Jr.. The effect of bronchitis, smoking, and occupation on ventilation. Am Rev Respir Dis 1963; 87: 684–693. 9 Savani BN, Montero A, Wu C, Nlonda N, Read E, Dunbar C et al. Prediction and prevention of transplant-related mortality from pulmonary causes after total body irradiation and allogeneic stem cell transplantation. Biol Blood Marrow Transplant 2005; 11: 223–230. 10 Ho VT, Weller E, Lee SJ, Alyea EP, Antin JH, Soiffer RJ. Prognostic factors for early severe pulmonary complications after hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 2001; 7: 223–229. 11 Feldman C, Anderson R. Cigarette smoking and mechanisms of susceptibility to infections of the respiratory tract and other organ systems. J Infect 2013; 67: 169–184.
Supplementary Information accompanies this paper on Bone Marrow Transplantation website (http://www.nature.com/bmt)
© 2015 Macmillan Publishers Limited
Bone Marrow Transplantation (2015) 1141 – 1143
LETTER TO THE EDITOR
Tobacco smoking is associated with infectious pulmonary complications after allogeneic hematopoietic stem cell transplantation Bone Marrow Transplantation (2015) 50, 1141–1143; doi:10.1038/ bmt.2015.116; published online 18 May 2015 Table 1.
Although encouraging survival statistics are now reported after allogeneic hematopoietic stem cell transplantation (allo-HSCT), pulmonary complications represent major causes of morbidity and mortality.1 Smoking is known to be associated with increased risk of various diseases, and can be a risk factor for respiratory tract infection in immunocompetent patients.2 In patients with AML, smoking has been reported to increase the rate of pulmonary infections during induction chemotherapy.3 In allo-HSCT, several studies have reported the impact of smoking on transplant outcomes. Some reports have reported smoking before allo-HSCT to be correlated with poor transplant outcomes such as lower overall survival (OS),4,5 disease-free survival (DFS)4 and increased non-relapse mortality (NRM) or disease relapse.4 Conversely, other studies have shown no apparent association between smoking and mortality after HSCT.6,7 An association between smoking and post-transplant pulmonary complications has also been reported in some studies. However, these reports were limited to only severe cases, and the clinical impact of smoking on the entire spectrum of pulmonary complications remains unclear. Therefore, we retrospectively analyzed 286 patients aged ⩾ 20 years with hematological disorders who underwent their first allo-HSCT at our hospital between 2005 and 2010. We evaluated the impact of tobacco smoking before allo-HSCT on clinical outcomes, with particular focus on pulmonary complications. The tobacco consumption of each patient was evaluated by the Brinkman Index (BI).8 The BI was calculated by multiplying the number of cigarettes smoked per day by the duration of smoking (years). The study patients were classified into three smoking groups according to BI: never smokers (BI = 0, n = 126); low-dose smokers (0 oBI o 400, n = 93) and high-dose smokers (BI ⩾ 400, n = 67). For patients with ⩾ 2 pulmonary events, only the first event was analyzed. Patient characteristics are summarized in Table 1. The patients in the high-dose smokers group were older, predominantly male and received reduced-intensity regimen and tacrolimus-based GvHD prophylaxis more frequently than the patients in the other groups (Table 1). Neither forced expiratory volume in 1 s nor percent of predicted forced vital capacity values were significantly different among the three groups. The median follow-up period after HSCT was 1165 days (36–2375 days). Ninety patients eventually developed pulmonary complications at a median of 184.5 days (7–803 days) after HSCT. The cumulative incidence of pulmonary complications was 26% in the never smokers group, 36% in the low-dose smokers group and 46% in the high-dose smokers group (P = 0.02, Figure 1a). Pulmonary complications seemed to develop in a dose-dependent manner. High-dose smoking (BI ⩾ 400) was significantly associated with a higher incidence of pulmonary complications in both univariate (relative risk (RR) 2.02, 95% confidence interval (CI) 1.21–3.35, P o0.01) and multivariate analysis (RR 1.78, 95% CI 1.06–3.00, P = 0.03) (Supplementary Table 1). The BI score was also associated with
Patient characteristics Never smokers
P-valuea
Smokers Low-dose (BI, 1–399)
High-dose (BI ⩾ 400)
126 (44%)
93 (33%)
67 (23%)
Age, years Median Range
42 21–68
36 20–73
54 34–69
o0.01
Sex Male Female
41 85
69 24
61 6
o0.01
Disease riskb Low High
67 59
35 58
29 38
0.07
Stem cell source Bone marrow Peripheral blood Cord blood
98 14 14
62 17 14
53 5 9
0.26
Donor type Related Unrelated
38 88
29 64
11 56
0.07
Conditioning regimen Myeloablative TBI Non-TBI Reduced intensity
42 58 26
42 33 18
28 17 22
0.03
0.02
No. of patients
GvHD prophylaxis Cyclosporinebased Tacrolimus-based
72
54
25
54
39
42
% of predicted FEV1 ⩾ 80% o80% Unknown
118 6 2
87 5 1
60 4 3
0.94
% of predicted FVC ⩾ 80% o80% Unknown
122 2 2
89 3 1
64 0 3
0.38
Abbreviations: BI = Brinkman index; FEV1 = forced expiratory volume in 1 s; FVC = forced vital capacity. aCategorical variables were compared using the χ2-test and continuous variables were compared using the Kruskal–Wallis test. bLow-disease risk included acute leukemia in first CR, CML in first chronic phase, myelodysplasia refractory anemia, malignant lymphoma in CR and nonmalignant hematologic diseases; whereas high-disease risk included all other diagnoses.
Letter to the Editor
1142 Never smokers Low dose smokers High dose smokers
0.8 0.6 0.4 0.2
c
1.0
Never smokers Low dose smokers High dose smokers
0.8 0.6 0.4 0.2 0.0
0.0 1 2 3 4 5 6 Years after transplantation
1 2 3 4 5 6 Years after transplantation
0.8 0.6 0.4 0.2
0
1 2 3 4 5 6 Years after transplantation
e
d Cumulative incidence of relapse
Never smokers Low dose smokers High dose smokers
0.0 0
1.0
Never smokers Low dose smokers High dose smokers
0.8 0.6 0.4 0.2
1.0 Adjusted probability of disease free survival
0
1.0
Cumulative incidence of non-relapse mortality
b
1.0
Adjusted probability of overall survival
Cumulative incidence of pulmonary complication
a
Never smokers Low dose smokers High dose smokers
0.8 0.6 0.4 0.2 0.0
0.0 0
1 2 3 4 5 6 Years after transplantation
0
1 2 3 4 5 6 Years after transplantation
Figure 1. Cumulative incidence of pulmonary complications (a), adjusted probability of OS (b), NRM (c), the cumulative incidence of relapse (d), and adjusted probability of DFS (e) after allo-HSCT according to smoking dose. Adjusted probabilities of OS and DFS were compared using the Cox proportional hazards regression model. Cumulative incidences of pulmonary complications, NRM and relapse were estimated using the cumulative incidence function method and compared using Gray’s test.
pulmonary complications in both univariate (RR 1.01, 95% CI 1.00–1.01, P o0.01) and multivariate analysis (RR 1.01, 95% CI 1.00–1.01, P = 0.02), even when BI was treated as a continuous variable (Supplementary Table 1). Pneumonia was the main cause of pulmonary complications, and occurred in 17% of patients in the never smokers group, 25% in the low-dose smokers group and 33% in the high-dose smokers group (P = 0.02, Supplementary Table 2). The rates of other causes of pulmonary complications, including non-infectious complications, were almost similar among the three groups, although the number of patients was limited. In previous studies, smoking has been reported to be a significant risk factor for the development of pulmonary complications after allo-HSCT. Savani et al.9 reported that pretransplant smoking history was associated with increased NRM from pulmonary causes, most of which were idiopathic pneumonia syndrome. Similarly, Tran et al.7 reported that smoking dose was linked with an increased risk of respiratory failure within 100 days after transplantation. Conversely, Ho et al.10 showed that smoking history was not associated with increased severe pulmonary complications, defined as diffuse alveolar hemorrhage, need for mechanical ventilation, or death from respiratory failure. These differences in findings may be owing to the definition of pulmonary complications and the subject population of the studies. However, the results of the present study indicate that smoking can increase the risk, not only for life-threatening pulmonary events, but also for the entire range of posttransplant pulmonary complications, especially for pulmonary infections. Impaired mucociliary clearance, reduced phagocytosis and lower secretion of cytokines by alveolar macrophages observed in smokers may promote their susceptibility to pulmonary infections after allo-HSCT.11 In addition, microbial virulence and antibiotic resistance promoted by smoking may also Bone Marrow Transplantation (2015) 1141 – 1143
advance the development of post-transplant pulmonary infections.11 In the present study, OS adjusted for age, sex, type of conditioning regimen and GvHD prophylaxis was similar among the three groups (Figure 1b). Disease relapse/progression was the most common cause of death, and pneumonia was the second or third leading cause of death in all three groups (Supplementary Table 3). NRM at 3 years after allo-HSCT was 20%, 22% and 24% (P = 0.84, Figure 1c), and the cumulative incidence of relapse at 3 years was 29%, 25% and 35% in the never, low-dose and high-dose smokers groups, respectively (P = 0.36, Figure 1d). DFS adjusted for age, sex, conditioning regimen and GvHD prophylaxis was similar among the three groups (Figure 1e). Several studies have examined the association between cigarette smoking and post-transplant survival or relapse. In a large retrospective study of CML patients by Marks et al.,4 high-dose smoking was associated with significantly reduced OS, DFS and increased NRM. Ehlers et al.5 also reported that current smoking appeared to adversely affect OS. However, the results of the present study showed that pre-transplant high-dose smoking did not affect OS, DFS and NRM. In the study by Marks et al., all patients were conditioned by a myeloablative regimen and bone marrow transplantation was performed more frequently compared with the patients in the present study. In addition, smoking dose did not affect the post-transplant outcomes in unrelated HSCT.4 Ehlers et al.5 analyzed acute leukemia patients, including those undergoing both autologous and allogeneic transplantation; the majority of the patients were conditioned by cyclophosphamide and TBI. The present study included various hematological malignancies. Furthermore, 208 of 286 (72%) patients received HSCT from unrelated donors and 66 (23%) patients were conditioned by a reduced-intensity conditioning regimen. © 2015 Macmillan Publishers Limited
Letter to the Editor
1143 Thus, differences between patients and transplant backgrounds may affect the outcomes. With regard to disease relapse, study results have been somewhat conflicting. Smoking was associated with disease relapse in some studies6,7 but not in another study4 or in the present study. These discrepancies may also be due to differences between patients and transplant backgrounds. The present study had some limitations. First, given the retrospective nature of the study, some pulmonary complications may have been missed despite the detailed database and extensive chart review. In addition, we analyzed only the first episode if the patients had multiple pulmonary events. Thus, the incidence of late-onset pulmonary complications may have been underestimated. The second limitation is that the heterogeneous backgrounds of the patients may have biased our results, although we adjusted the factors in the multivariate analyses. The third limitation is that we could not follow the patients’ smoking status after allo-HSCT, which might influence transplant outcomes. In summary, the findings of the present study indicated that pretransplant tobacco smoking as measured by BI is an independent risk factor for the development of infectious pulmonary complications in a dose-dependent manner after allo-HSCT. Further prospective studies are warranted to confirm whether early smoking cessation would decrease the incidence of pulmonary complications after allo-HSCT. CONFLICT OF INTEREST The authors declare no conflict of interest.
ACKNOWLEDGEMENTS We are very grateful to the patients who participated in this study. We would like to thank the nursing staff at the Tokyo Metropolitan Cancer and the Infectious Diseases Center, Komagome Hospital for their excellent patient care.
R Hanajiri, K Kakihana, T Kobayashi, N Doki, H Sakamaki and K Ohashi Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan E-mail: [email protected] REFERENCES 1 Lucena CM, Torres A, Rovira M, Marcos MA, de la Bellacasa JP, Sanchez M et al. Pulmonary complications in hematopoietic SCT: a prospective study. Bone Marrow Transplant 2014; 49: 1293–1299. 2 Nuorti JP, Butler JC, Farley MM, Harrison LH, McGeer A, Kolczak MS et al. Cigarette smoking and invasive pneumococcal disease. Active Bacterial Core Surveillance Team. N Engl J Med 2000; 342: 681–689. 3 Chelghoum Y, Danaila C, Belhabri A, Charrin C, Le QH, Michallet M et al. Influence of cigarette smoking on the presentation and course of acute myeloid leukemia. Ann Oncol 2002; 13: 1621–1627. 4 Marks DI, Ballen K, Logan BR, Wang Z, Sobocinski KA, Bacigalupo A et al. The effect of smoking on allogeneic transplant outcomes. Biol Blood Marrow Transplant 2009; 15: 1277–1287. 5 Ehlers SL, Gastineau DA, Patten CA, Decker PA, Rausch SM, Cerhan JR et al. The impact of smoking on outcomes among patients undergoing hematopoietic SCT for the treatment of acute leukemia. Bone Marrow Transplant 2011; 46: 285–290. 6 Chang G, Orav EJ, McNamara T, Tong MY, Antin JH. Depression, cigarette smoking, and hematopoietic stem cell transplantation outcome. Cancer 2004; 101: 782–789. 7 Tran BT, Halperin A, Chien JW. Cigarette smoking and outcomes after allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 2011; 17: 1004–1011. 8 Brinkman GL, Coates EO Jr.. The effect of bronchitis, smoking, and occupation on ventilation. Am Rev Respir Dis 1963; 87: 684–693. 9 Savani BN, Montero A, Wu C, Nlonda N, Read E, Dunbar C et al. Prediction and prevention of transplant-related mortality from pulmonary causes after total body irradiation and allogeneic stem cell transplantation. Biol Blood Marrow Transplant 2005; 11: 223–230. 10 Ho VT, Weller E, Lee SJ, Alyea EP, Antin JH, Soiffer RJ. Prognostic factors for early severe pulmonary complications after hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 2001; 7: 223–229. 11 Feldman C, Anderson R. Cigarette smoking and mechanisms of susceptibility to infections of the respiratory tract and other organ systems. J Infect 2013; 67: 169–184.
Supplementary Information accompanies this paper on Bone Marrow Transplantation website (http://www.nature.com/bmt)
© 2015 Macmillan Publishers Limited
Bone Marrow Transplantation (2015) 1141 – 1143
