Advertisement

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

Thomas H. Price, Michael Boeckh, Ryan W. Harrison, Jeffrey McCullough, Paul M. Ness, Ronald G. Strauss, W. Garrett Nichols, Taye H. Hamza, Melissa M. Cushing, Karen E. King, Jo-Anne H. Young, Eliot Williams, Janice McFarland, Jennifer Holter Chakrabarty, Steven R. Sloan, David Friedman, Samir Parekh, Bruce S. Sachais, Joseph E. Kiss and Susan F. Assmann

Key points

  • Overall, no benefit of granulocyte transfusion therapy was observed, but the power of the study was reduced due to low accrual.

  • Post-hoc secondary analysis suggested that patients receiving higher doses tended to have better outcomes than patients receiving lower doses.

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 54.9x109 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 ≥0.6x109 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.

  • Submitted May 15, 2015.
  • Accepted August 6, 2015.