Efficacy of transfusion with granulocytes from G-CSF/dexamethasone-treated donors in neutropenic patients with infection
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.
Increased preoperative collection of autologous blood with recombinant human erythropoietin therapy
New England Journal of Medicine. 1989;321((17):):1163-8.
To study whether the administration of recombinant human erythropoietin increases the amount of autologous blood that can be collected before surgery, we conducted a randomized, controlled trial of erythropoietin in 47 adults scheduled for elective orthopedic procedures. The patients received either erythropoietin (600 units per kilogram of body weight) or placebo intravenously twice a week for 21 days, during which time up to 6 units of blood was collected. Patients were excluded from donation when their hematocrit values were less than 34 percent. All patients received iron sulfate (325 mg orally three times daily). The mean number of units collected per patient (+/- SE) was 5.4 +/- 0.2 for the erythropoietin group and 4.1 +/- 0.2 for the placebo group. The mean red-cell volume donated by the patients who received erythropoietin was 41 percent greater than that donated by the patients who received placebo (961 vs. 683 ml, P less than 0.05). Only 1 of the 23 patients treated with erythropoietin was unable to donate greater than or equal to 4 units (4 percent) as compared with 7 of the 24 patients who received placebo (29 percent). No adverse effects were attributed to erythropoietin. We conclude that recombinant human erythropoietin increases the ability of patients about to undergo elective surgery to donate autologous blood.