RBC transfusion has an immune-modulating ef­fect.29 RBC transfusion may be associated with in­creased risks of postoperative infections, longer dura­tions of hospital stay, and longer stays in the ICU.28,30,31 RBC transfusion has also been linked to longer dura­tions of mechanical ventilation, increased incidences of multiple organ failures, and an overall increase in health care costs.28,30-33 However, these issues have not been resolved. In the previous few years, concerns have been raised that RBC transfusions might exac­erbate cancer; however, no consensus has yet to be made on this issue. For more information about this topic, please read the article by Drs. Dasararaju and Marques in this issue.

The rationale for the transfusion of RBCs is to increase the delivery of oxygen to the tissues, but physiological changes with RBC storage may limit this goal. In addition, the ability of transfused RBCs to de­liver oxygen to areas most in need of oxygenation may be decreased.33 The physiological changes that occur in stored RBCs (collectively called the RBC storage lesion) may limit, to some degree, the ability of the transfused RBCs to enter the microcirculation and may decrease vasodilation by altering the bioavailability of nitric oxide. During storage, RBCs undergo changes that result in their removal from the circulation within 24 hours of transfusion. However, some RBCs recover biochemical normalcy and survive normally.34 Other changes to stored RBCs include microparticle forma­tion, changes in shape, decreased concentration of RBC 2,3-diphosphoglycerate, decreased pH, and the decreased availability of adenosine triphosphate and glucose. In combination, the physiological changes resulting from the RBC storage lesion may limit the delivery of oxygen by the transfused RBCs. However, no consensus exists on whether RBCs stored for long periods of time are deleterious to any patient group; thus, RBCs of any storage age can be used for patients with cancer. Leukoreduced RBCs have decreased rates of transfusion reactions, HLA alloimmunization, and have the potential benefit of modifying the transfu­sion-related immune modulation (TRIM) effect (if it exists). Thus, leukoreduced RBCs are recommended as the standard blood product for routine use in pa­tients with cancer.

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Frequent transfusions for cancer and chemo­therapy treatments over an extended period of time may result in iron overload. Treatment regimens for many solid organ cancers avoid this complication because the transfusion-dependent period is short­er in duration due to chemotherapy and irradiation regimens.34,35 As transfusion dependence increases during treatment, the risk of transfusion-transmitted infection, allergic response, and severe transfusion reactions increase with each unit transfused. Health care professionals must weigh any benefit from RBC transfusions against these risks.

Special Red Blood Cell Products

Patients with cancer may require specially prepared RBC products due to frequent comorbidities.

Leukoreduced Blood Components

The leukocyte content of different blood products widely varies (as high as 1 × 109 in whole blood to <0.6 × 106 in fresh frozen plasma [FFP]). Leukoreduced blood products are blood products produced by filtration or apheresis to decrease the number of leukocytes remaining in the product to below 5 × 106 leukocytes/component.36 Leukoreduced blood com­ponents are beneficial in 3 ways: (1) decreased fre­quency of febrile nonhemolytic transfusion reactions, (2) decreased HLA sensitization of recipients, and (3) decreased likelihood of cytomegalovirus (CMV) transmission via transfusion.37

Leukoreduction may significantly reduce febrile nonhemolytic transfusion reactions and may decrease cardiopulmonary transfusion reactions (transfu­sion-related acute lung injury and transfusion-associ­ated circulatory overload).38,39 Presumably, this occurs through reduced levels of bioactive lipids and soluble CD40L in leukoreduced RBCs, which would have been produced by leukocytes had they remained in the blood product.40 As the RBCs age in storage media, they develop well-established changes that include decreased deformability and decreased levels of ade­nosine triphosphate and 2,3 diphosphoglycerate. Do­nor leukocytes release cytokines and lipid mediators capable of affecting neutrophils in a time-dependent course during RBC storage.41 Prestorage leukoreduc­tion decreases the release of metabolites and cellular components into the RBC product.

Leukoreduction may also be effective in decreasing alloimmunization and platelet transfusion refractoriness. This is especially relevant to patients with cancer as they may receive numerous RBC and platelet transfu­sions during their treatment cycle. A study published in 1997 examined 1,047 patients with acute myeloid leukemia.42 Those who received leukoreduced plate­lets had decreased levels of lymphocytotoxic antibodies and lower rates of refractoriness to platelet transfusion when compared with the study controls who received unmodified pooled platelet concentrates.42

Leukoreduction may decrease the TRIM effect of blood transfusion that may lead to possible increased cancer recurrence. Evidence suggesting that blood transfusion may decrease immune function was estab­lished more than 30 years ago, showing that survival rates were increased following renal transplantation.29 Other, more controversial data exist regarding RBC transfusion and tumor recurrence perioperatively. Vamvakas and Carven31 showed that patients with col­orectal cancer who received RBC transfusion periop­eratively had longer lengths of hospital stays when adjusted for multiple confounding factors related to the severity of their illness, difficulty of operation, and risks for postoperative infections. In addition, Blajch­man32 reported adverse effects on tumor recurrence in 50% of nonrandomized trials. Further data suggest that an immunomodulatory role in transfusion is related to a dose-dependent association (ie, increased RBC transfusion) with postoperative bacterial infections and RBC transfusion.30