Granulocyte Transfusions in Children With Chronic Granulomatous Disease and Invasive Aspergillosis

Abstract

The transfusion of granulocytes to restore host defenses in severely granulocytopenic patients or in patients with defective granulocyte functions has been studied for more than 60 years. However, inadequate dosage of cells and inconsistent efficacy has limited the usage of these transfusions. Recently, the use of mobilizing agents such as granulocyte colony stimulating factors and dexamethasone has renewed interest in these treatment modalities. The present study is conducted to determine an appropriate method of enriched granulocyte collection with Fresenius AS.TEC.204 cell separator (Fresenius, Bad Homburg, Germany) and to evaluate the preliminary clinical results of granulocyte transfusion therapy in patients with chronic granulomatous disease and invasive Aspergillosis in parallel with in vitro granulocyte function. Three patients who have been treated for chronic granulomatous disease and invasive Aspergillosis received a total of 20 granulocyte transfusions. To mobilize granulocytes, healthy donors were given 450 microg of granulocyte colony-stimulating factor (G-CSF) subcutaneously and 8 mg of dexamethasone orally approximately 12 h before collection. Five microg/kg/day of G-CSF was also subcutaneously administered prior to granulocyte transfusions. The first patient received 4; the second, 14 and the third, 2 transfusions. The granulocyte count given to these patients ranged between 0.4 and 3.0 x 10(9)/kg. Most transfusions were well tolerated. The nitroblue tetrazolium (NBT) tests that were done 16-24 h after the transfusion showed 14-46% dye reduction. Two of the three patients survived the infection. Granulocyte transfusions from G-CSF and dexamethasone stimulated donors could be a choice of treatment in chronic granulomatous disease patients, especially with disseminated invasive Aspergillosis.

Invasive fungal infections in congenital immunodeficiencies

“…Limited clinical data also suggest a role for granulocyte transfusions from healthy donors in order to partially restore the patients' impaired phagocytic activity [32][33][34]. Finally, appropriate surgical debridement should not be delayed when needed, particularly in cases of localized (liver abscess and osteomyelitis) or aggressive lung infection [16].…”

Fungal infections in primary immunodeficiencies

“…The use of granulocyte colony-stimulating factor (G-CSF) has markedly enhanced the yield of leucocytes from healthy donors and helped to optimize granulocyte dose per patient body weight. Preliminary clinical data appear encouraging, although well-designed clinical trials are still lacking [13,17,66,67]. If administered, granulocyte transfusions should be given several hours apart from amphotericin B, in order to avoid the risk of pulmonary leukostasis [185].…”

Experimental Evidence That Granulocyte Transfusions Are Efficacious in Treatment of Neutropenic Hosts with Pulmonary Aspergillosis

“…The genetic identity removes the possible complications of graft-versus-host disease (necessitating, in humans, radiation of the WBC) and alloimmunization (44). We are less aware of infusion-related side effects (none were noted) and unaware of any as subjectively reported in humans (3,27).…”

“…Although there is a lack of convincing controlled trial data (6,12), reviews of case studies and small trials would speak to a role for granulocyte transfusions in addition to antifungal or antibacterial therapy, with positive results in up to 70% of patients. Open trials in mycoses in neutropenia (2) and favorable results in fungal infections in chronic granulomatous disease patients are particularly relevant (27)(28)(29). Treatment protocols and recommendations vary among investigators (6,12).…”