Infection remains one of the leading causes of death in the hematologic malignancies, and the transfusion of granulocytes to the neutropenic, infected patient has been attempted with varying levels of success as a therapeutic adjunct.73-77 Typically, granulocytes are collected from normal donors by apheresis techniques using hydroxyethyl starch (HES) following corticosteroid administration.10 73 74 Corticosteroid administration to the normal donor enhances the number of granulocytes collected, and HES is a red cell sediment-ing agent that promotes separation of the granuloctyes from contaminating red cells during collection. The final product should contain at least 1 X 1010 granulocytes.10 Granulocytes should be maintained at 20-24°C without agitation, and must be transfused within 24 h of collection. Once initiated, a course of granulocyte transfusion therapy should be continued at least daily for 4-5 days. Granulocytes should be administered through a standard blood infusion set, but leukocyte-reduction filters are contraindicated. If a CMV-safe granulocyte product is desired then the donor's CMV status must be determined, although the importance of testing the donor for CMV has been questioned by some.78 79 Granulocytes contain significant amounts of contaminating red blood cells and should thus be ABO and Rh compatible with the recipient. If the recipient also has red cell alloantibodies, then the donor's red cells should be negative for the corresponding antigen(s). If necessary, granulocytes can be irradiated prior to administration.
The indications for granulocyte transfusion typically include patients who have (1) a polymorphonuclear leukocyte (PMN) count <500/^L, (2) a documented infection, and (3) are unresponsive to antibiotic therapy (generally for at least 48 h).73'74'77 It is also expected that the patient, and his or her bone marrow, will recover once the infection is controlled. Most patients will experience FNH transfusion reactions during or following granuolocyte transfusion. In addition, a significant percentage of recipients will develop antileukocyte antibodies following repeated granulocyte transfusions. Pulmonary reactions (e.g., infiltrates, hypoxia, or dyspnea) are also commonly seen after granulocyte transfusions.73 74 77 These reactions can often be treated symptomatically, but more severe adverse reactions, such as transfusion-related acute lung injury (TRALI), can also be seen.80 Although not commonly reported following granulocyte transfusion, TRALI can cause significant morbidity and mortality. The administration of amphotericin B in close proximity to granulocyte transfusions has been reported to cause pulmonary reactions.73 77 This has been disputed but, when feasible, separating the administration of both by several hours seems prudent.
The prophylactic use of granulocytes has not been supported by most randomized studies in the literature.73-77 In addition, not all types of infection respond equally to a course of granulocyte transfusion therapy. For example, fungal infections appear to be less responsive than bacterial infections.73-77 Because of the conflicting data on efficacy, the use of granulocytes has decreased over the years. More recent studies have focused on the number of granulocytes collected from donors. With the ready availability of granulocyte colony-stimulating factor (G-CSF), increased interest has been directed towards using G-CSF, with or without concurrent dexamethasone administration, to stimulate the formation and collection of larger numbers of PMNs in donors.81-83 Several studies have demonstrated the feasibility of collecting large numbers of PMN's from normal donors, but the efficacy of granulocytes collected in this manner remains to be proven.84 In addition, the side effects associated with G-CSF administration has raised ethical concerns of its usage in otherwise healthy donors.85 The use of G-CSF in normal donors should only be performed as part of formal research protocols, and a national donor registry should be established to collect safety and efficacy data.85
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