title: Dose-Dependent Effect of Granulocyte Transfusions in Hematological Patients with Febrile Neutropenia.
abstract: It is still under debate whether granulocyte transfusions (GTs) substantially increase survival in patients with febrile neutropenia. We retrospectively examined data relative to 96 patients with hematological malignancies receiving 491 GTs during 114 infectious episodes (IE). Patients were grouped according to the median doses of granulocytes transfused during the infectious episode (low-dose group: <1.5-x108 cells/Kg; standard-dose group: 1.5-3.0x108 cells/Kg and high-dose group: >3.0x108 cells/Kg). The impact of clinical, microbiological and GT-related variables on the infection-related mortality (IRM) was investigated. The IRM was not influenced by the number of GTs or by the total amount of granulocytes received, whereas a dose-related effect of the median dose received for IE was detected at univariate analysis (IRM of 18.4% in the standard-dose group, 44.4% in the low-dose group and 48.4% in the high-dose group, p = 0.040) and confirmed at multivariate analysis (OR 3.7, IC 95% 1.5-8.9; 0.004 for patients not receiving standard doses of GTs). Moreover, patients receiving GTs at doses lower or greater than standard had increased risk for subsequent ICU admission and reduced overall survival. The dose-related effect of GTs was confirmed in bacterial but not in fungal infections. Preliminary findings obtained from a subgroup of patients candidate to GTs revealed that levels of inflammatory response mediators increase in a dose-related manner after GTs, providing a possible explanation for the detrimental effect exerted by high-dose transfusions. GTs can constitute a valuable tool to improve the outcome of infections in neutropenic patients, provided that adequate recipient-tailored doses are supplied. Further investigations of the immunomodulatory effects of GTs are recommended.
authors.affiliation: Institute of Hematology, Catholic University, Rome, Italy.
authors.forename: Luciana
authors.identifier: http://orcid.org/0000-0002-7214-1561
authors.initials: L
authors.lastname: Teofili
authors.affiliation: Institute of Hematology, Catholic University, Rome, Italy.
authors.forename: Caterina Giovanna
authors.initials: CG
authors.lastname: Valentini
authors.affiliation: Institute of Hematology, Catholic University, Rome, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Di Blasi
authors.affiliation: Institute of Hematology, Catholic University, Rome, Italy.
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Orlando
authors.affiliation: Institute of Hematology, Catholic University, Rome, Italy.
authors.forename: Luana
authors.initials: L
authors.lastname: Fianchi
authors.affiliation: Institute of Hematology, Catholic University, Rome, Italy.
authors.forename: Gina
authors.initials: G
authors.lastname: Zini
authors.affiliation: Institute of Hematology, Catholic University, Rome, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Sica
authors.affiliation: Institute of Hematology, Catholic University, Rome, Italy.
authors.forename: Valerio
authors.initials: V
authors.lastname: De Stefano
authors.affiliation: Institute of Hematology, Catholic University, Rome, Italy.
authors.forename: Livio
authors.initials: L
authors.lastname: Pagano
mesh_terms: D000328:Adult; D000368:Aged; D016207:Cytokines / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D064147:Febrile Neutropenia / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D005260:Female; D006098:Granulocytes / Q000276:immunology; D006402:Hematologic Diseases / Q000150:complications* / Q000276:immunology; D006801:Humans; D017708:Leukocyte Transfusion / Q000379:methods*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D016019:Survival Analysis; D055815:Young Adult
chemical_list: D016207:Cytokines