Neutrophils are an integral component of the innate immune system and key regulators of cell-mediated defense against bacterial and fungal pathogens. The potential of granulocyte transfusions has been investigated to temporarily replenish innate immune function to prevent and/or treat infections in patients with severe neutropenia or neutrophil dysfunction. However, evidence has been largely theoretical, experimental, and/or inconclusive. Clinical efficacy has yet to be confirmed by large-scale randomized controlled clinical trials. Performing such trials has been hampered by low granulocyte collection yield and poor patient accrual. We provide a practical summary of the current literature surrounding the practice of granulocyte transfusion.
Temporarily neutropenic patients with life-threatening, drug-resistant bacterial or fungal infections may benefit from granulocyte transfusions.
Granulocyte transfusion therapy requires a high degree of multidisciplinary coordination to optimize outcomes.
To date, randomized controlled trials have failed to demonstrate the efficacy of granulocyte transfusion; however, uncontrolled studies show potential benefit.
The term granulocyte is broadly applicable to white blood cells (WBCs) demonstrating cytoplasmic granules, referring not only to neutrophils, but also basophils, eosinophils, and mast cells. The latter 3 cell types rarely circulate in large numbers but are integral to the host defense against parasitic infections, allergens, and noxious stimuli. Neutrophils are by far the most numerous granulocyte and play a critical role in the immune defense against fungal and bacterial pathogens. Patients with impaired neutrophil function, either as a result of congenital deficits, neonatal infection, or as a result of chemotherapy or hematopoietic progenitor cell transplant, are at significant risk of morbidity and mortality after infection from an invasive pathogen. The development of bacterial and/or fungal infection in neutropenic patients is known to be associated with prolonged hospitalization, end-organ damage, and increased mortality. Furthermore, prolonged neutropenia is a poor prognostic indicator after hematopoietic progenitor cell transplantation. ,
The transfusion of allogeneic granulocytes to provide innate immune support represents a logical therapeutic modality for patients with innate immune depression. However, the clinical usefulness of granulocyte transfusion (GTX) has long been debated, with reports suggesting clinical usefulness published as early as the 1930s. To date no randomized controlled clinical trials have demonstrated the efficacy of GTX. , However, some retrospective and observational studies suggest GTX may improve outcomes in specific populations of neutropenic patients with active infection.
Unfortunately, the interpretation of the studies performed to date has been hampered by multiple limitations, particularly those associated with variances in granulocyte collection, including, but not limited to, the evolution of donor stimulation and collection regimens, profound advancements, and modifications to patient care regimens, and poor patient accrual potentially owing to physician bias and an unwillingness to subject patients to randomization. Herein we provide a practical guide for practice of GTX.