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/μL) 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 × 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 × 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.
Department of Medicine, University of Washington, Seattle, WA; Bloodworks Northwest, Seattle, WA;
Thomas H
TH
Price
Department of Medicine, University of Washington, Seattle, WA; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA;
Michael
M
Boeckh
New England Research Institutes, Watertown, MA;
Ryan W
RW
Harrison
Department of Laboratory Medicine and Pathology, Department of Medicine, University of Minnesota, Minneapolis, MN;
Jeffrey
J
McCullough
Department of Pathology, Division of Transfusion Medicine, Johns Hopkins Hospital, Baltimore, MD;
Paul M
PM
Ness
Department of Pathology, University of Iowa Hospital, Iowa City, IA;
Ronald G
RG
Strauss
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA; Chimerix Inc, Durham, NC;
W Garrett
WG
Nichols
New England Research Institutes, Watertown, MA;
Taye H
TH
Hamza
Department of Pathology, Weill Cornell Medical College, New York, NY;
Melissa M
MM
Cushing
Department of Pathology, Division of Transfusion Medicine, Johns Hopkins Hospital, Baltimore, MD;
Karen E
KE
King
Department of Laboratory Medicine and Pathology, Department of Medicine, University of Minnesota, Minneapolis, MN;
Jo-Anne H
JA
Young
Department of Medicine, University of Wisconsin, Madison, WI;
Eliot
E
Williams
BloodCenter of Wisconsin, Milwaukee, WI;
Janice
J
McFarland
Department of Medicine, University of Oklahoma, Oklahoma City, OK;
Jennifer
J
Holter Chakrabarty
Department of Laboratory Medicine, Boston Children's Hospital, Boston, MA;
Steven R
SR
Sloan
Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA;
David
D
Friedman
Division of Hematology-Oncology, Montefiore Medical Center, Bronx, NY;
Samir
S
Parekh
Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA; New York Blood Center, New York, NY;
Bruce S
BS
Sachais
Division of Medical Oncology and Hematology, University of Pittsburgh, Pittsburgh, PA; and Institute for Transfusion Medicine, Pittsburgh, PA.
Joseph E
JE
Kiss
New England Research Institutes, Watertown, MA;
Susan F
SF
Assmann
D000890:Anti-Infective Agents / Q000627:therapeutic use; D003907:Dexamethasone / Q000494:pharmacology; D005938:Glucocorticoids / Q000494:pharmacology; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D006098:Granulocytes / Q000166:cytology* / Q000187:drug effects; D006801:Humans; D007239:Infections / Q000150:complications* / Q000188:drug therapy; D007958:Leukocyte Count; D017708:Leukocyte Transfusion / Q000379:methods*; D009503:Neutropenia / Q000150:complications* / Q000628:therapy*; D016896:Treatment Outcome
D000890:Anti-Infective Agents; D005938:Glucocorticoids; D016179:Granulocyte Colony-Stimulating Factor; D003907:Dexamethasone