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

TitleEfficacy of transfusion with granulocytes from G-CSF/dexamethasone-treated donors in neutropenic patients with infection.
Publication TypeJournal Article
Year of Publication2015
AuthorsPrice TH, Boeckh M, Harrison RW, McCullough J, Ness PM, Strauss RG, W Nichols G, Hamza TH, Cushing MM, King KE, Young J-AH, Williams E, McFarland J, Chakrabarty JHolter, Sloan SR, Friedman D, Parekh S, Sachais BS, Kiss JE, Assmann SF
JournalBlood
Volume126
Issue18
Pagination2153-61
Date Published2015 Oct 29
ISSN1528-0020
KeywordsAnti-Infective Agents, Dexamethasone, Glucocorticoids, Granulocyte Colony-Stimulating Factor, Granulocytes, Humans, Infections, Leukocyte Count, Leukocyte Transfusion, Neutropenia, Treatment Outcome
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/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.

DOI10.1182/blood-2015-05-645986
Alternate JournalBlood
PubMed ID26333778
PubMed Central IDPMC4626256
Grant ListHL072321 / HL / NHLBI NIH HHS / United States
U01 HL072346 / HL / NHLBI NIH HHS / United States
HL072290 / HL / NHLBI NIH HHS / United States
U01 HL072305 / HL / NHLBI NIH HHS / United States
U01 HL072028 / HL / NHLBI NIH HHS / United States
HL072268 / HL / NHLBI NIH HHS / United States
UL1 TR000427 / TR / NCATS NIH HHS / United States
HL072196 / HL / NHLBI NIH HHS / United States
U01 HL072291 / HL / NHLBI NIH HHS / United States
HL072283 / HL / NHLBI NIH HHS / United States
HL072191 / HL / NHLBI NIH HHS / United States
HL072072 / HL / NHLBI NIH HHS / United States
U01 HL072290 / HL / NHLBI NIH HHS / United States
HL072346 / HL / NHLBI NIH HHS / United States
HL072305 / HL / NHLBI NIH HHS / United States
U01 HL072283 / HL / NHLBI NIH HHS / United States
U01 HL072072 / HL / NHLBI NIH HHS / United States
R01 HL072321 / HL / NHLBI NIH HHS / United States
HL072291 / HL / NHLBI NIH HHS / United States
U01 HL072191 / HL / NHLBI NIH HHS / United States
U01 HL072196 / HL / NHLBI NIH HHS / United States
HL072028 / HL / NHLBI NIH HHS / United States
U01 HL072268 / HL / NHLBI NIH HHS / United States
Related Faculty: 
Melissa Cushing, M.D.

Pathology & Laboratory Medicine 1300 York Avenue New York, NY 10065 Phone: (212) 746-6464
Surgical Pathology: (212) 746-2700