Both the observational studies and the RCTs yielded contradictory findings, and, because of the discrepancies between the published studies, the long-standing hypothesis of a deleterious TRIM effect of perioperative ABT remains unresolved. The mechanism(s) of the TRIM effect(s) also remains or remain elusive. The specific blood constituent(s) that mediate(s) the TRIM effect(s) is or are unknown. The more than 100 observational studies comparing transfused and untransfused patients, and the 2 RCTs comparing recipients of allogeneic and autologous blood 6,8,10 have not attributed the TRIM effect to any particular blood constituent. These studies examined whether a TRIM effect exists, regardless of whether the effect is mediated by allogeneic plasma, allogeneic leukocytes, or the components of the white cell storage lesion (i.e., soluble mediators originating in leukocyte granules 14 or membranes 15 and accumulating in a time-dependent manner during storage). The Viral Activation Transfusion Study (VATS) 16 specifically investigated the effect of immunologically active allogeneic leukocytes, transfusing RBC units stored for less than 2 weeks so that they would contain intact leukocytes. None of the other RCTs comparing recipients of nonleukoreduced versus autologous or leukoreduced RBCs 7,9,11-13 had used fresh units to similarly attribute the TRIM effect to intact leukocytes. Thus, it is impossible to extricate the effect of allogeneic leukocytes from the effects of allogeneic plasma or leukocyte-derived soluble mediators in these studies.
17To enhance transfusion safety, universal prestorage leukoreduction of all transfused cellular blood components has been implemented in Canada, Japan, and several European countries. If TRIM really caused deleterious effects, these would affect many (or potentially all) transfused patients. Thus, if TRIM was really mediated by allogeneic leukocytes, it would be appropriate to implement universal leukoreduction for the prevention of adverse TRIM effects.18 Moreover, it would be appropriate to implement prestorage leukoreduction, for the prevention of the white cell storage lesion, if there were evidence to suggest that leukocyte deterioration during storage is associated with adverse TRIM effects.14,15 The purpose of this review is to examine the clinical evidence as to whether a deleterious TRIM effect exists and can be abrogated by leukoreducing transfused cellular blood components.
RCTs on ABT and Cancer RecurrenceThe three RCTs 6-8 that examined the association between ABT and cancer recurrence were medically and statistically homogeneous.1 All three studies enrolled patients undergoing colorectal cancer resection. In each study, approximately 60% of the patients were transfused and approximately 25% developed cancer recurrence. There is also agreement among the findings of the RCTs in that the observed differences in the reported results is sufficiently modest to be attributed to chance. (There is a > 10% probability that the discrepancies between the studies might have ari...