1.
WBC alloimmunization: effects on the laboratory and clinical endpoints of therapeutic granulocyte transfusions
Price T H, McCullough J, Strauss R G, Ness P M., Hamza T H, Harrison R W, Assmann S F
Transfusion. 2018;58((5):):1280-1288
Abstract
BACKGROUND Although the subject of many previous studies, the importance of white blood cell (WBC) alloimmunization in granulocyte transfusion therapy has not been settled. In this study, we report the results of the effects of WBC antibodies in the RING (Resolving Infection in Neutropenia with Granulocytes) study, a randomized controlled trial comparing the efficacy of daily granulocyte transfusion therapy plus antimicrobials versus antimicrobials alone; the primary outcome results have been published previously. STUDY DESIGN AND METHODS One hundred fourteen subjects were enrolled in the study. Serum samples for WBC antibody determination were obtained from each subject at baseline and at 2 and 6 weeks. One hundred subjects had at least one antibody test result. Samples were tested for human leukocyte antigen (HLA) Class I and Class II antibodies as well as for granulocyte-specific antibodies using granulocyte agglutination and immunofluorescence techniques. All testing was performed at a central laboratory. RESULTS Baseline WBC alloimmunization was modest, depending somewhat on the assay. Seroconversion during the study was slightly higher in the granulocyte transfusion arm, but the differences were not statistically significant. There was no demonstrable effect of the presence of alloimmunization on the primary outcome (survival and microbial response at 42 days), the occurrence of transfusion reactions (either overall or pulmonary), or posttransfusion neutrophil increments. CONCLUSION The presence or development of WBC antibodies had no demonstrable effect on any clinical aspect of granulocyte transfusion therapy. It appears that, at least in the patient population studied, there is no evidence suggesting need for concern about recipient WBC alloimmunization when prescribing granulocyte transfusions.
2.
Efficacy of transfusion with granulocytes from G-CSF/dexamethasone-treated donors in neutropenic patients with infection
Price TH, Boeckh M, Harrison RW, McCullough J, Ness PM, Strauss RG, Nichols WG, Hamza TH, Cushing MM, King KE, et al
Blood. 2015;126((18)):2153-61.
Abstract
High-dose granulocyte transfusion therapy has been available for 20 years, yet its clinical efficacy has never been conclusively demonstrated. We report here the results of RING (Resolving Infection in Neutropenia with Granulocytes), a multicenter randomized controlled trial designed to address this question. Eligible subjects were those with neutropenia (absolute neutrophil count <500/muL) and proven/probable/presumed infection. Subjects were randomized to receive either (1) standard antimicrobial therapy or (2) standard antimicrobial therapy plus daily granulocyte transfusions from donors stimulated with granulocyte colony-stimulating factor (G-CSF) and dexamethasone. The primary end point was a composite of survival plus microbial response, at 42 days after randomization. Microbial response was determined by a blinded adjudication panel. Fifty-six subjects were randomized to the granulocyte arm and 58 to the control arm. Transfused subjects received a median of 5 transfusions. Mean transfusion dose was 54.9 x 10(9) granulocytes. Overall success rates were 42% and 43% for the granulocyte and control groups, respectively (P > .99), and 49% and 41%, respectively, for subjects who received their assigned treatments (P = .64). Success rates for granulocyte and control arms did not differ within any infection type. In a post hoc analysis, subjects who received an average dose per transfusion of >0.6 x 10(9) granulocytes per kilogram tended to have better outcomes than those receiving a lower dose. In conclusion, there was no overall effect of granulocyte transfusion on the primary outcome, but because enrollment was half that planned, power to detect a true beneficial effect was low. RING was registered at www.clinicaltrials.gov as #NCT00627393. Copyright © 2015 by The American Society of Hematology.
3.
A randomized controlled trial on the efficacy of high-dose granulocyte transfusion therapy in neutropenic patients with infection
Price TH, McCullough J, Ness P, Strauss RG, Pulkrabek SM, Harrison R, Hamza T, Assman S
Blood. 2014;124((21)): Abstract No. 1354
4.
A controlled trial of prophylactic granulocyte transfusions during initial induction chemotherapy for acute myelogenous leukemia
Strauss RG, Connett JE, Gale RP, Bloomfield CD, Herzig GP, McCullough J, Maguire LC, Winston DJ, Ho W, Stump DC, et al
New England Journal of Medicine. 1981;305((11):):597-603.
Abstract
To evaluate the role of prophylactic granulocyte transfusions during remission-induction chemotherapy for acute myelogenous leukemia (AML) we randomized 102 infected patients either to receive daily granulocyte transfusions when blood granulocytes fell below 0.5 x 10(9) per liter (54 patients) or not to receive them (48). Although the percentage of patients acquiring any infection was similar in the transfusion and control groups (46 and 42 per cent, respectively), granulocyte transfusions decreased the proportion of patients with bacterial septicemia (9 per cent of those with transfusions vs. 27 per cent of the controls; P = 0.01). Granulocyte transfusions did not reduce the incidence of other infections or improve bone-marrow recovery, remission rate and duration, or survival. Seventy-two per cent of the patients given transfusions had transfusion reactions. Pulmonary infiltrates were more common in the transfusion group than in the control group (57 per cent vs. 27 per cent; P = 0.002). Thirty-five per cent of the patients with pulmonary filtrates died, as compared with 5 per cent of those without filtrates. We conclude that prophylactic granulocyte transfusions should not be used during remission-induction chemotherapy in AML because the risks outweigh the benefits.