J.G.A. Houbiers

Beneficial Effects of Leukocyte Depletion of Transfused Blood on Postoperative Complications in Patients Undergoing Cardiac Surgery A Randomized Clinical Trial

BACKGROUND Leukocytes in transfused blood are associated with several posttransfusion immunomodulatory effects. Although leukocytes play an important role in reperfusion injury, the contribution of leukocytes in transfused blood products has not been investigated. To estimate the role and the timing of leukocyte filtration of red cells in cardiac surgery, we performed a randomized study. METHODS AND RESULTS Patients scheduled for cardiac surgery were randomly allocated to receive either packed cells without buffy coat (PC, n = 306), fresh-filtered units (FF, n = 305), or stored-filtered units (SF, n = 303) when transfusion was indicated. We evaluated the periods of hospitalization and stay at the intensive care unit, and the occurrences of postoperative complications up to 60 days after surgery. The average hospital stay was 10.7 days, of which 3.2 days were in the intensive care unit, without significant differences between the groups. In the PC trial arm, 23.0% of the patients had infections versus 16.9% and 17.9% of the patients in the leukocyte-depleted trial arms (P=.13). Within 60 days, 45 patients had died, 24 patients in the PC trial arm (7.8%), versus 11 (3.6%) and 10 (3.3%) patients in the FF and SF trial arms, respectively (P=.015). CONCLUSIONS In cardiac surgery patients, especially when more than three blood transfusions are required, leukocyte depletion by filtration results in a significant reduction of the postoperative mortality that can only partially be explained by the higher incidence of postoperative infections in the PC group.

Randomised controlled trial comparing transfusion of leucocyte-depleted or buffy-coat-depleted blood in surgery for colorectal cancer

In retrospective studies, perioperative blood transfusions were associated with poor prognosis after surgery for cancer and were a major independent risk factor for postoperative bacterial infection. Leucocyte-depleted, in contrast to buffy-coat-depleted, blood has no immunosuppressive effects in transplantation and so might lack detrimental effects on cancer prognosis and postoperative infections. We studied this hypothesis in a controlled trial by randomly allocating patients to receive either leucocyte-depleted red cells or packed cells without buffy coat when blood was needed. Between 1987 and 1990, 871 eligible patients with colorectal cancer, including 697 patients operated upon with curative intent, were randomised in the 16 participating hospitals. Neither the eligible group nor the curative group showed significant differences between the two trial transfusions in survival, disease-free survival, cancer recurrence rates, or overall infection rates after an average follow-up of 36 months. Patients who had a curative resection and who received blood of any sort had a lower 3-year survival than non-transfused patients (69% vs 81%, p = 0.001) and a higher infection rate (39% vs 24%, p < 0.001). Colorectal cancer recurrence rates, however, were not influenced by blood transfusion (30% vs 26%, p = 0.22). These combined observations confirm the association between blood transfusion and poor patient survival but indicate that the relation is not due to promotion of cancer.

Transfusion of red cells is associated with increased incidence of bacterial infection after colorectal surgery: a prospective study

BACKGROUND: Several studies suggest that perioperative blood transfusion is a major independent risk factor for postoperative bacterial infections. Transfusion‐induced immunosuppression is thought to mediate this effect. STUDY DESIGN AND METHODS: In a randomized clinical trial comprising 697 patients with colorectal cancer, the relationship between two types of red cell components (buffy coat‐ depleted packed red cells and white cell‐reduced [filtered] packed red cells) and postoperative bacterial infections was analyzed. RESULTS: Both types of red cells appeared to be associated with a greater incidence of postoperative infection than was no transfusion (39 vs. 24%, p < 0.01). A dose‐response relationship could be demonstrated: the corrected relative risk was 1.6 for 1 to 3 units of red cells and 3.6 for more than 3 units. Multivariate analyses identified the transfusion of red cells and tumor location as the only significant independent risk factors for postoperative bacterial infection. CONCLUSION: Because allogeneic white cells, plasma, microaggregates, citrate, and platelets could be ruled out as risk factors for transfusion‐associated postoperative infections, it is hypothesized that the transfusion of red cells is a potentially detrimental factor that transiently impairs the clearance of bacteria by phagocytic cells.

p53, a potential target for tumor-directed T cells

Cell lineage-specific cellular proteins, oncogenes from viral or cellular origin and tumor suppressor genes encode tumor-specific/associated antigens. Such antigens can elicit an major compatibility complex (MHC) class I-restricted cytotoxic T lymphocyte (CTL) response, either naturally in cancer patients or following appropriate immunostimulation (in vitro or in vivo). The reported immune responses in humans to the melanoma-associated MAGE gene products, GP100 and tyrosinase, all self-proteins, support the idea to use wild-type p53 products as targets for T cells. An important step towards this goal is identification of potential p53 CTL epitopes. We identified the wild-type p53 peptides with the highest affinity to the HLA-A*0201 molecule using two assays: the previously described MHC peptide-binding assay and the peptide competition assay. We obtained CTL against four p53 peptides with a high affinity for the HLA-A*0201 molecule. These findings are discussed next to a short review concerning the p53 literature.

Blood Transfusion and Cancer: Modulation or Tolerance?

The concept of immunosurveillance has evoked a wide spread interest in the role of the immune system in the natural history of cancer. Clinical data from immunodeficient [1] and immunosuppressed [2] patients show an increased incidence of malignancy. Blood transfusions (BT) have diverse immunomodulating effects. For instance, pre-transplant random-donor BT diminish the incidence of renal allograft rejection [3,4] and can give rise to leukocyte antibodies [5]. Several essential factors and clues for the mechanisms of this BT induced immunosuppression in allograft transplantation have recently been elucidated, but the precise mechanism(s) remains unclear. Combining these observed phenomena Gantt raised the question whether immunomodulating effects of peri-operative blood transfusion might adversely affect the prognosis of cancer patients [6]. Surgical resection of tumours often requires blood transfusion. In case of a curative operation, the primary tumour is removed, but nevertheless a percentage of the patients will develop distant metastases [7]. Minimal residual disease in the form of undetectable micrometastases and/or tumour cells spilled in the operation region or into the circulation during surgery might be explanations for these observations. However, not all patients having a similar cancer stage show recurrence of the tumour. Probably minimal residual disease not always results in cancer recurrence. It is suggested that besides tumour characteristics and genetics the immune defense might play a role in the outgrowth of micrometastases. Before addressing possible mechanisms the relationship between blood transfusion and cancer prognosis has to be clarified on a clinical level (the horizontal arrow in (Figure 1).