Correlation Between Perioperative Blood Transfusion and Prognosis of Patients Subjected to Surgery for Stage I Lung Cancer* Mario Nosotti, MD; Paolo Rebulla, MD; Donatella Riccardi, MD; Alessandro Baisi, MD; Nadia Bellaviti, MD; Lorenzo Rosso, MD; and Luigi Santambrogio, MD Background: It has been reported, but not proven, that perioperative blood transfusions have a detrimental effect on the survival of patients undergoing surgery for lung cancer. Study design and methods: A prospective study was carried out on the patients undergoing lobectomy for stage I lung cancer at our department from 1995 to 2000. The criteria for exclusion included previous cases of malignancy, autoimmune diseases, and any other relevant comorbidity. Results: Two hundred eighty-one patients were observed, 24.6% of whom received transfusions. The only significant difference between the transfused and nontransfused patients was their preoperative hemoglobin (Hb) concentration (12.5  1.20 g/dL vs 13.3  1.22 g/dL, p < 0.001). The disease-free interval of the transfused patients was significantly lower than that of the nontransfused patients (53% vs 78% at 73 months, p < 0.005), as was also the case for actuarial survival (52% vs 71% at 73 months, p < 0.02). Blood transfusion was significantly predictive of tumor relapse according to the Cox model adjusted for the T state, preoperative Hb concentration, sex, age, histologic type, and grading (hazard ratio, 2.3; p  0.017). Conclusions: Our data show that perioperative blood transfusion is significantly correlated to worse prognosis in patients undergoing surgery for stage I lung cancer. (CHEST 2003; 124:102–107) Key words: blood transfusion; lung neoplasms; recurrence Abbreviations: Hb  hemoglobin; TRIM  allogeneic blood transfusion-associated immunomodulation B etween 1986 and 1994, numerous observational studies investigated the effects of blood transfu- sion on the survival of patients undergoing pulmo- nary resection for cancer. Nonetheless, the attractive hypothesis that the nonspecific immunosuppression caused by transfusion 1 may support tumor growth and lower survival has not been definitively prov- en. 2–9 The immune disorder caused by blood trans- fusion is nonetheless a clinical phenomenon that is well described in the medical literature and goes by the name allogeneic blood transfusion-associated im- munomodulation (TRIM). 10 In addition to the field of oncology, TRIM also appears to be involved in the improved survival of transplanted kidneys, the re- duction of relapses in Crohn disease, the higher incidence of postoperative bacterial infections, and the activation of cytomegalovirus infections. The majority of retrospective (or partially retrospec- tive 9 ) observational studies that have analyzed the relationship between TRIM and lung cancer tend to demonstrate that patients who receive transfusions during the perioperative period have a higher mortality rate and/or higher incidence of tumor relapse than patients who do not receive transfusions. However, in these studies it is possible to observe that the transfused patients differ from the nontransfused patients in terms of several important prognostic factors, such as clinical stage, frequency of systemic diseases, and extent of surgery. Consequently, despite the use of multivariate statistical models of regression, the reported adverse effect of perioperative blood transfusion may be influ- enced by known and unknown confounding factors. 11 In 1995, we commenced a prospective observational study on a selected sample of patients undergoing *From the Thoracic Surgery Unit (Drs. Nosotti, Baisi, Bellaviti, Rosso, and Santambrogio), Centro Trasfusionale e di Immuno- logia dei Trapianti (Drs. Rebulla and Riccardi), I.R.C.C.S. Os- pedale Maggiore Policlinico, Milan, Italy. Manuscript received July 8, 2002; revision accepted October 24, 2002. Reproduction of this article is prohibited without written permis- sion from the American College of Chest Physicians (e-mail: permissions@chestnet.org). Correspondence to: Mario Nosotti, MD, Thoracic Surgery Unit, Ospedale Maggiore Policlinico, I.R.C.C.S. Via F. Sforza, 35, 20122 Milan, Italy; e-mail: marionosotti@libero.it 102 Clinical Investigations