Efficacy of transfusion with granulocytes from G-CSF/dexamethasone treated donors in neutropenic patients with infection.

Abstract:

High-dose granulocyte transfusion therapy has been available for twenty years, yet its clinical efficacy has never been conclusively demonstrated. We report here the results of RING, a multi-center randomized controlled trial designed to address this question. Eligible subjects were those with neutropenia (ANC<500/uL) 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 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 54.9x10(9) granulocytes. Overall success rates were 42% and 43% for the granulocyte and control groups, respectively (p> 0.99), and 49% and 41%, respectively, for subjects who received their assigned treatments (p=0.64). 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 ≥0.6x10(9) granulocytes/kg 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.