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Studies of associations between periopcrativc blood transfusions and later recurrence of solid tumors have yielded conflicting results. A previous analysis of transfused patients suggested that recurrence was associated with transfusion of whole blood as opposed to red blood cell concentrates. Additional analyses were performed on patients with cancers of the colon, rectum, cervix, and prostate to determine if patients receiving whole blood, red blood cells only, or no transfusions had differing outcomes. Patients receiving 1 unit or more of whole blood had uniformly poor outcomes compared with nontransfused patients (p < 0.001). In contrast, patients receiving only red blood cells had progressively worse recurrence and death rates with increasing numbers of transfusions, suggesting the presence of a dose-effect relationship. Employing multivariate techniques, blood transfusions of $$3 units that included any whole blood were independently and significantly associated with earlier recurrence (p = 0.003) and death due to cancer (p = 0.02). Transfusions of $$3 units of blood comprised solely of red blood cell concentrates were associated with no greater risk of recurrence than that seen in patients receiving no transfusions (p = 0.50). These results provide a potential explanation for the disparate results reported in studies of blood transfusion and cancer outcome. The marked difference in outcome seen between patients receiving a few units of red blood cells and comparable patients receiving even one unit of whole blood are consistent with the hypothesis that transfusion of stored blood plasma causes earlier tumor recurrence in some instances. Strategics for reducing these risks might include avoidance of whole blood transfusions when only 1–3 units are required, more conservative transfusion practice, use of autologous blood transfusions, and perhaps, use of red blood cells washed free of plasma and white cell debris. Clinical trials to test these hypotheses are urgently needed.