Blood donation leads to a decrease in natural killer cell activity: a study in normal blood donors and cancer patients.

Transfusion-induced immunosuppression has long been known to be beneficial for organ transplantation patients, but recent retrospective studies suggest that blood transfusions may be detrimental for patients with cancer. If autologous blood is used to avoid immunosuppression, the assumption is that the procedure, involving blood donation, is immunologically neutral. In the present study, this assumption was evaluated by monitoring 33 normal blood donors and 16 colorectal cancer patients before and after donation of 1 (500 mL) and 2 units of blood, respectively. The cancer patients belonged to the autologous arm of a randomized trial in which the effects of allogeneic versus autologous blood on cancer prognosis were studied. The patients donated 2 units of blood with an interval of 3 to 4 days between donations. Flow cytometric analysis revealed that blood donation by normal donors and cancer patients had no effect on the proportion of B, T, and natural killer (NK) cells. Only the total number of lymphocytes was significantly decreased in the normal donors on Day 12 after donation. Blood donation had no significant effect on T-cell function assessed by phytohemagglutinin stimulation in normal donors or in cancer patients donating 2 units of blood. A significant depression of NK cell function (88% and 74% of predonation levels) was observed in normal donors on Days 2 and 5 after donation; on Day 12, the activity was again normal. Colorectal cancer patients had a significantly depressed NK cell activity (54% of predonation activity) on Day 12 after the first donation.(ABSTRACT TRUNCATED AT 250 WORDS)

The influence of blood loss on tumour growth: effect and mechanism in an experimental model.

Retrospective studies have provided indirect evidence that allogeneic blood transfusion may adversely influence the prognosis of cancer patients. This effect may be prevented by using autologous blood transfusions. However, this involves preoperative donation of blood, the consequences of which are still unknown. The aim of the present study was to investigate the possible effects of blood loss on tumour growth and on NK-cell activity. An artificial lung metastasis model was used in the BN rat from which 20 per cent of the blood volume was taken at different time intervals. The results showed that blood loss, one day prior to tumour challenge, had a profound stimulating effect on tumour growth. After blood loss, the number of lung metastases was doubled as compared to controls. This tumour-promoting effect could be prevented by an immediate plasma transfusion, but not by evoking a normal haemoglobin level after blood loss by pretreatment with recombinant erythropoietin (rEpo). The NK-cell activity of spleen cells was significantly depressed, 24 hours after blood loss. At a 50:1-lymphocyte-to-target cell ratio, the NK-cell activity dropped from 25.3 per cent in controls to 9.3 per cent in experimental animals. Since NK-cells are assumed to play a role in the clearance of tumour cells from the circulation, the enhanced tumour growth observed after blood loss might be caused by this depression.

Efficacy of recombinant erythropoietin for stimulating erythropoiesis after blood loss and surgery. An experimental study in rats.

Perioperative administration of recombinant human erythropoietin (rEpo) may reduce the need for allogeneic blood transfusions by diminishing the time lag between blood loss and erythropoiesis and by generating more adequate Epo levels. The efficacy of pre- and postoperative rEpo was studied in rats subjected to blood loss (20% of the blood volume) and surgery (ileal resection). After 200 U rEpo/kg daily for 5 days postoperatively, hemoglobin had increased by 15.7 g/l in these rats but by 36.9 g/l in rEpo-treated controls without surgery (p less than 0.05), indicating an inhibitory effect of surgery on erythropoiesis. A course of 200 U rEpo/kg/day for 5 days, starting 4 or 2 days before operation and blood loss, resulted in significantly higher postoperative hemoglobin levels than in untreated controls. Such difference did not occur if rEpo treatment was begun on the day of operation. Prolonged (10-day) postoperative rEpo treatment was of minor benefit, inducing significant increase in hemoglobin and hematocrit only from day 8 onwards. The study indicates that rEpo is a promising agent to obviate need for perioperative blood transfusions, provided that the treatment is begun before operation.

Blood transfusions and prognosis in colorectal cancer.

BACKGROUND: Blood transfusions may adversely affect the prognosis of patients treated surgically for cancer, although definite proof of this adverse effect has not been reported. METHODS: We carried out a randomized trial to investigate whether the prognosis in patients with colorectal cancer would be improved by a program of autologous blood transfusion as compared with the current practice of allogeneic transfusion. Patients in the autologous-transfusion group were required to donate two units of blood before surgery. RESULTS: A total of 475 patients were evaluated. We found no significant difference in prognosis between the allogeneic-transfusion group (236 patients) and the autologous-transfusion group (239 patients); colorectal cancer-specific survival rates at four years were 67 percent and 62 percent, respectively (P = 0.39). Among the 423 patients who underwent curative surgery, 66 percent of those in the allogeneic-transfusion group and 63 percent of those in the autologous-transfusion group had no recurrence of colorectal cancer at four years (P = 0.93). We also found that the risk of recurrence was significantly increased in patients who received blood transfusions, either allogeneic or autologous, as compared with patients who did not require transfusions; the relative rates of recurrence were 2.1 (P = 0.01) and 1.8 (P = 0.04), respectively; these rates did not differ significantly from each other. CONCLUSIONS: The use of autologous blood as compared with allogeneic blood for transfusion does not improve the prognosis in patients with colorectal cancer. Regardless of their type, transfusions are associated with poor prognosis, probably because of the circumstances that necessitate them.

Feasibility of a predeposit autologous blood donation program in colorectal cancer patients: results from a randomized clinical study.

The hematologic and transfusion data of a multicenter randomized trial investigating the effect of blood transfusions on the 5-year survival were used to study the feasibility of an autologous blood donation program in colorectal cancer patients. Three hundred and ten patients were randomized for autologous blood transfusions (predeposition of 2 units) or homologous blood transfusions, and transfusion rules were standardized. The Hb level in the patients who donated blood decreased by 20.1 +/- 1.3 g/l (mean +/- SEM) preoperatively and 4.5 +/- 1.8 g/l postoperatively, and in controls 3.7 +/- 1.1 g/l and 16.5 +/- 1.9 g/l (significantly different between the two groups, both pre- and postoperatively: p less than 0.01). Because blood loss and number of transfusions were similar in both groups, this indicated that either preoperative or postoperative erythropoiesis is stronger in patients who had donated blood. Twenty-three percent of the autologous patients and 61% of the homologous patients were exposed to homologous blood. The effectiveness of the procedure differed per tumor localization. In patients with a right-sided colon carcinoma, 22% of the control patients needed homologous blood, compared to 10% of the autologous patients. In patients with other colon carcinomas, this was 52 and 16%, respectively, and in patients with a rectal carcinoma 85 and 41%. We conclude that predeposition of 2 units of blood for colorectal cancer surgery is feasible and useful to prevent homologous blood usage in a significant number of patients with left colon carcinoma or rectal carcinoma.