Modulation of immune response by blood transfusion: evidence for a differential effect of allogeneic and autologous blood in colorectal cancer surgery.

Even though blood transfusion-associated immunomodulatory effects have been reported, the basic immune mechanism is still not understood. Data from studies on the clinical effects of allogeneic blood-induced immunosuppression are contradictory. However, there are indications that autologous blood transfusion is not immunologically neutral but has intrinsic immunomodulatory potential. Therefore we investigated in vivo different immunological mediators in 56 randomized patients of a study comparing autologous and allogeneic blood transfusion in colorectal cancer surgery. Soluble IL-2 receptor, which is an indicator of general immune activation and the following immunologic refractory phase, indicated immunosuppression was more elevated at the seventh postoperative day in patients with allogeneic transfusions (p = .013) and autologous transfusions (p = .0003). The immunologic determination of TNF-alpha showed a significant postoperative increase in patients with autologous transfusions only (p = .0031). However, postoperative increase of soluble TNF-receptors p55 and p75 was also significant in patients transfused with allogenic blood (p = .022; p = .0014). The response to tetanus toxoid vaccination, an indicator of humoral immunity, was higher in patients transfused with allogeneic rather than autologous blood (p = .082), whereas responses of patients with autologous transfusions were even lower than in nontransfused patients. The reciprocal was already found for cell-mediated immunity determined by epicutaneously tested delayed-type hypersensitivity-reactions. IL-10 levels, an indicator of cellular immunosuppression, were determined in 27 additional patients before operation, immediately postoperative, and at the seventh postoperative day. IL-10 was found elevated immediately postoperative in allogeneic (p = .011) and nontransfused patients only (p = .042). The data from this study substantiate recent findings of a different immunomodulatory potential of allogeneic and autologous blood transfusion. They furthermore support the hypothesis that autologous blood transfusion does not contain immunologically neutral effects of allogeneic blood, but itself exerts an immunomodulatory effect.

Perisurgical erythropoietin application in anemic patients with colorectal cancer: A double-blind randomized study.

BACKGROUND: Blood transfusions are associated with higher postoperative morbidity and tumor recurrence rates in colorectal cancer surgery, To reduce the need for transfusions in patients with tumor-induced anemia who are not suitable for autologous blood donation, it was tested whether perisurgical erythropoietin application would be able to stimulate hematopoiesis adequately. METHODS: In a double-blind randomized study 150 IU/kg body weight erythropoietin was given subcutaneously every 2 days beginning 10 days before operation and continuing until postoperative day 2. Twenty patients were randomized into the erythropoietin group with three observed dropouts and 10 patients into the placebo group. RESULTS: In the erythropoietin group two episodes of hypertension and one deep venous thrombosis were observed. Preoperative hemoglobin response in the erythropoietin group (p = 0.069) was paralleled by a highly significant reticulocyte increase (p = 0.0004). However, frequency of blood transfusion was not different between both study groups (erythropoietin, 1.82 +/- 0.80 units/ patient; placebo, 1.80 +/- 0.97 units/patient). If iron availability was analyzed, a strong correlation between ferritin blood levels and transferrin iron saturation with hemoglobin response was observed in regression analysis (p < 0.001). CONCLUSIONS: These results indicate that hematopoiesis in anemic patients with colorectal cancer can be stimulated by erythropoietin; however, clinical efficacy is to be expected only in selected patients with high iron availability, which calls for further studies combining erythropoietin and parenteral iron application.

Blood transfusion-modulated tumor recurrence: first results of a randomized study of autologous versus allogeneic blood transfusion in colorectal cancer surgery.

PURPOSE: Allogeneic blood transfusions have reportedly been associated with a poor prognosis in patients with curatively resected cancer. To control for immunosuppression induced by a speculatively causal allogeneic blood transfusion, we designed a randomized study in which the control group received autologous blood transfusions not related to any condition of immunosuppression. PATIENTS AND METHODS: One hundred twenty patients with potentially curative resectable colorectal cancer and the capability to predeposit autologous blood were randomly selected to receive either standard allogeneic blood transfusion or predeposited autologous blood. RESULTS: In curatively resected cancer patients, the number who needed allogeneic blood transfusions was reduced from 60% in the allogeneic blood group to 33% in the autologous blood group (P = .009). After a median follow-up duration of 22 months (range, 8 to 48) tumor recurrence was observed in 28.9% of the allogeneic blood group and 16.7% of the autologous blood group. Life-table analysis established a tendency toward a shorter tumor-free survival for the allogeneic blood group (log-rank P = .11). The problem with this analysis was the strong association of allogeneic blood transfusions with tumor recurrence, which interfered in 33% of patients in the autologous blood group who required additional allogeneic blood transfusions. Multivariate analysis of established risk factors for tumor recurrence and surgery-related variables reflecting potential immunosuppressive conditions showed that only pT stage (relative risk, 6.61; 95% confidence interval [CI], 1.82 to 23.99; P = .004), pN stage (relative risk, 8.39; 95% CI, 3.15 to 22.33; P < .001), and the need for allogeneic blood (relative risk, 6.18; 95% CI, 2.20 to 17.37; P < .001) were independent predictors of tumor recurrence. Subgroup analysis of patients who received a transfusion of < or = 2 U blood found a significantly higher risk of tumor recurrence in the allogeneic blood group (relative risk, 5.16; 95% CI, 1.13 to 23.62; P = .034), which was reduced to borderline significance (relative risk, 3.54; 95% CI, 0.76 to 16.51; P = .107) by adjustment for tumor (T) and node (N) stage. CONCLUSION: As indicated by these first results, the blood transfusion modality has a significant effect on tumor recurrence after surgical treatment of colorectal cancer. A change in the practice of blood transfusion might thus potentially surpass the impact of any recent adjuvant treatment strategies.

Beneficial effect of autologous blood transfusion on infectious complications after colorectal cancer surgery.

Homologous blood transfusion has been associated with an increased risk of postoperative infectious complications. To test the clinical consequences of this apparently immunosuppressive effect of homologous blood in a controlled trial, we designed a study in which the control group deposited autologous blood before their operations for use should transfusion be needed. We enrolled 120 patients with apparently curable colorectal cancer who were able to predeposit autologous blood (haemoglobin > 12.5 g/dL). 62 patients were assigned to receive homologous blood if blood transfusions were needed during operation, and the other 58 to receive their own predeposited blood followed, if necessary, by homologous blood [corrected]. Despite the similarity between the groups in factors known to affect the risk of postoperative infections, there was a significant difference in postoperative infection rate between the homologous and autologous blood groups (17 [27%] vs 7 [12%], p < 0.05; unadjusted odds ratio 2.75 [95% CI 1.07-7.11). The rates of non-infectious complications were similar Probably because their preoperative blood depositing caused the autologous blood patients to have lower haemoglobin concentrations, they were more likely to require transfusion than were the homologous blood group (53 [91%] vs 37 [60%], p < 0.001; relative risk 1.53 [1.24-1.89]). 20 (35%) required homologous as well as autologous blood. To adjust for the many infection-related factors, we did multivariate regression analysis; tumour location, preoperative ASA index, and study group assignment were the only significant risk factors. The odds ratio for postoperative infections adjusted for these factors was 2.84 (1.02-7.98, homologous vs autologous). Testing of delayed-type hypersensitivity responses before and after surgery showed decreases in both mean diameter and number of positive reactions in recipients of homologous blood and slight increases in those who received autologous blood. This study shows the clinical potential of blood-transfusion-mediated immunomodulation, which may be important also in tumour immunology.

[Clinical effects of blood transfusion-associated immune modulation on outcome of tumor surgery]. / Klinische Auswirkungen der mit einer Bluttransfusion assoziierten Immunmodulation auf das Ergebnis der Tumoroperation.

Extended experimental studies revealed different immunological mechanisms which are possibly responsible for blood transfusion-associated immunosuppressive conditions. To expect a clinical impact of these mechanisms on the course of tumor disease, it is necessary to postulate (1) that immunological mechanisms have a significant role in controlling tumor growth and (2) that blood transfusion-induced immunmodulation is long lasting. Both postulates are supported by recent reports and are the rationales of clinical studies indicating that blood transfusion is a risk factor for postoperative infections and tumor recurrence. Since all studies have been retrospective or uncontrolled, we performed a prospective controlled study in randomized groups of patients suffering from colorectal cancer and compared the effects of allogeneic and autologous blood transfusions. The results indicate that patients treated with allogeneic blood transfusion had significantly higher rates of postoperative infectious complications than patients who received autologous blood. Our preliminary follow-up observations found a trend towards higher tumor-free survival in patients treated with autologous blood which is statistically significant in subgroup analysis.