Blood Transfusion Promotes Cancer Progression : A Critical Role for Aged Erythrocytes

• Published in: Anesthesiology (Philadelphia) Vol. 109; no. 6; pp. 989 - 997
• Main Authors: ATZIL, Shir, ARAD, Michal, GLASNER, Ariella, ABIRI, Noa, AVRAHAM, Roi, GREENFELD, Keren, ROSENNE, Ella, BEILIN, Benzion, BEN-ELIYAHU, Shamgar
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 01-12-2008
• Subjects: Adenocarcinoma - blood; Adenocarcinoma - secondary; Adenocarcinoma - therapy; Anesthesia; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Animals; Biological and medical sciences; Cell Line, Tumor; Disease Progression; Erythrocyte Aging - physiology; Erythrocyte Transfusion - adverse effects; Erythrocytes - pathology; Erythrocytes - physiology; Female; Leukemia, Experimental - blood; Leukemia, Experimental - pathology; Leukemia, Experimental - therapy; Lung Neoplasms - blood; Lung Neoplasms - secondary; Lung Neoplasms - therapy; Male; Mammary Neoplasms, Experimental - blood; Mammary Neoplasms, Experimental - secondary; Mammary Neoplasms, Experimental - therapy; Medical sciences; Neoplasms - blood; Neoplasms - pathology; Rats; Rats, Inbred F344; Rats, Wistar; Anesthesia; Transfusion; Malignant tumor; Cancer
• ISSN: 0003-3022; 1528-1175
• DOI: 10.1097/aln.0b013e31818ddb72

In cancer patients, allogeneic blood transfusion is associated with poorer prognosis, but the independent effect of the transfusion is controversial. Moreover, mediating mechanisms underlying the alleged cancer-promoting effects of blood transfusion are unknown, including the involvement of donors' leukocytes, erythrocytes, and soluble factors.
Two syngeneic tumor models were used in Fischer 344 rats, the MADB106 mammary adenocarcinoma and the CRNK-16 leukemia. Outcomes included host ability to clear circulating cancer cells, and host survival rates. The independent impact of blood transfusion was assessed, and potential deleterious characteristics of the transfusion were studied, including blood storage duration; the role of erythrocytes, leukocyte, and soluble factors; and the kinetics of the effects.
Blood transfusion was found to be an independent and significant risk factor for cancer progression in both models, causing up to a fourfold increase in lung tumor retention and doubling mortality rates. Blood storage time was the critical determinant of these deleterious effects, regardless of whether the transfused blood was allogeneic or autogenic. Surprisingly, aged erythrocytes (9 days and older), rather than leukocytes or soluble factors, mediated the effects, which occurred in both operated and nonoperated animals. The effects of erythrocytes transfusion in the MADB106 model emerged immediately and dissipated within 24 h.
In rats, transfusion of fresh blood is less harmful than transfusion of stored blood in the context of progressing malignancies. Further studies should address mediating mechanisms through which erythrocytes' storage duration can impact the rate of complications while treating malignant diseases and potentially other pathologies.