Granulocytes are the immune system’s main cellular defense against bacterial and fungal infections. Granulocyte transfusions are used in patients with prolonged neutropenia or functional neutrophil disorders and severe bacterial and fungal infections. Granulocyte transfusion clinical efficacy is not established. However, granulocyte transfusions are still used in clinical management of neutropenic patients with bacterial or fungal infections that are refractory to standard antimicrobial therapy in some institutions.

Granulocyte products

  • contain >1 × 10 10 granulocytes, 10–30 mL of RBCs, and 1–6 × 10 10 platelets,

  • must undergo crossmatch and emergency release procedure, as results of infectious disease testing may be unknown at time of administration,

  • should be irradiated and cytomegalovirus (CMV)–matched to recipient, and

  • should be transfused within 24 hours of collection.

Indications

Owing to lack of high-quality data, indications primarily come from case series.

Neonatal Sepsis

Neonates are at risk for bacterial and fungal infection because of diminished storage pool of neutrophils, which can be rapidly depleted; neonates also have a qualitative defect of neutrophil function. In 1992, a clinical trial involving 35 neonates with neutropenia and sepsis randomized to receive either intravenous immunoglobulin (IVIG) (n = 14) or granulocyte transfusion (n = 21) found significantly higher survival in granulocyte transfusion group (100% survival) versus IVIG group (64% survival). Subsequently, more recent studies with newer antimicrobials have not demonstrated improvement in mortality; however, granulocyte dose transfused is the most significant factor predicting favorable outcome. In 2011, the Cochrane Collaboration concluded based on four randomized controlled trials published that there is inconclusive evidence to support granulocyte use in neonatal sepsis.

Neutrophil Function Defects

Patients whose neutrophils have defects in adhesion and motility may develop cutaneous abscesses with common pathogens such as Staphylococcus aureus, mucous membrane lesions caused by Candida albicans , or sepsis. Disorders of phagocytic microbicidal activity such as chronic granulomatous disease (CGD) are also associated with cutaneous and deep-seated abscesses, lymphadenitis, pulmonary infections, and sepsis. Granulocyte transfusions in CGD are supported by observation that a small number of normal neutrophils may be able to compensate for the metabolic defect in CGD neutrophils. Numerous case reports document the potential benefit of granulocyte transfusions in this patient population.

Neutropenia and Sepsis

Two randomized multicenter trials failed to demonstrate difference between standard antimicrobial therapy alone versus with granulocyte transfusion; however, both studies had poor accrual. In the European trial, 74 patients were randomized to receive standard antimicrobial therapy either with or without granulocyte transfusions (G-CSF–stimulated donors); no 28-day survival benefit was demonstrated. In the US Resolving Infection on Neutropenia with Granulocytes (RING) trial, 114 patients were randomized to receive standard antimicrobial therapy alone or with granulocytes (G-CSF and dexamethasone–stimulated donors) and demonstrated no survival difference. Although, post hoc analysis comparing subjects receiving high-dose versus low-dose granulocytes did achieve statistical significance. Cochrane review concluded there is low-grade evidence that therapeutic granulocyte transfusions may not increase clinical resolution of an infection.

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