ORIGINAL ARTICLE Single-donor granulocyte transfusions for improving the outcome of high-risk pediatric patients with known bacterial and fungal infections undergoing stem cell transplantation: a 10-year single-center experience O Nikolajeva 1 , A Mijovic 2 , D Hess 2 , E Tatam 2 , P Amrolia 1 , R Chiesa 1 , K Rao 1 , J Silva 1 and P Veys 1 Bacterial and fungal infections remain a significant cause of transplant-related mortality following allogeneic stem cell transplantation (SCT). Granulocyte transfusions (GTs) may reduce the neutropenic period after SCT and prevent further progression of the existing infection (that is, therapeutic GT) in addition to standard antibacterial and antifungal therapy. A retrospective analysis was performed on 28 consecutive pediatric SCT recipients who received at least one dose of GT between March 2003 and November 2013 at a single institution. All donors were conditioned with G-CSF+dexamethasone with harvest performed 12–18 h later. Indications for SCT were acute leukemia in 46% (13/28) and severe aplastic anemia in 21% (6/28). The main indications for GT were invasive fungal disease in 50%, bacterial infection in 21% and co-morbidities with predicted reduced tolerance to sepsis in 18% (5/28). The median number of GT was 6 (range 1–14) with a median dose of 3.56 × 10 10 granulocytes infused. The median increment in ANC was 1.06 × 10 9 /L and correlated with the granulocyte dose infused. Adverse reactions observed were mild and infrequent. Sixty-four percent of patients (18/28) are alive with only 2 of the 10 deaths being related to progression of infection. In addition there was a low overall incidence of grade 3–4 acute mucositis and a very low incidence (7%) of acute GvHD grade 3–4. Single-donor GTs afford protection to children undergoing SCT at additional risk of infection and may reduce the overall incidence of severe GvHD. Bone Marrow Transplantation (2015) 50, 846–849; doi:10.1038/bmt.2015.53; published online 30 March 2015 INTRODUCTION Infection associated with chemotherapy-induced neutropenia remains one of the major causes of allogeneic stem cell transplantation (SCT)-related morbidity and mortality. In some patients infections progress despite improved supportive care with broad-spectrum antibacterial and antifungal agents. Patients who are considered for allogeneic SCT and have pre-existing infections, carry an additional mortality risk. 1 Therapeutic transfu- sions of granulocytes from healthy donors have been used since 1970. However, demonstration of clinical benefit to patients has been inconsistent. The reasons for this include variable granulo- cyte doses, variable collection techniques and significant side effects, notably pulmonary infiltrates. In the late 1970s, three randomized controlled studies in infected neutropenic patients evaluated the response to treatment with antibiotics with or without theraupeutic granulocyte transfusions (GTs). The survival rate was higher in patients who received higher doses of granulocytes (41.7 × 10 10 /dose), 2–4 this was confirmed by later reports. 5–8 In studies of neonatal sepsis there was a survival benefit from using granulocytes obtained from centrifugation leukapheresis as opposed to buffy coat separation owing to a significantly higher dose obtained in the leukapheresis product. 9,10 Granulocyte donors mobilized with G-CSF and dexamethasone produced significantly higher yields of granulocytes. 5,7,11 Some studies concluded that bacterial infections responded well to the treatment with GTs but serious/invasive fungal infections with tissue damage responded poorly. 3,5,6,9,12 The timing and rate of GTs had a role, with early and more frequent administration of GTs leading to improved outcomes. 13,14 One of the significant drawbacks in early studies was the significant side effects observed in recipients. Some studies have confirmed the decreased risk of adverse reactions and increased efficacy of GTs partially matched for HLA antigens and ABO groups. 6,15 Van de Watering et al. 16 reported reduction of severe pulmonary toxicity after the introduction of the leukapheresis method for granulocyte collection. Few reports have been published on the efficacy of prophylactic GTs. A Cochrane review in 2009 by Massey et al. 13 concluded that higher doses of prophylactic GTs reduced the risk of mortality from infection. Adkins et al. 15,17 demonstrated some clinical benefits from prophylactic GTs if given daily and when no leukocyte antibodies were present in the recipients. Kerr et al. 11 used prophylactic GTs for eight patients with high risk of invasive fungal disease (IFD) in the allogeneic transplant setting and showed safety and efficacy of that approach. 1 Bone Marrow Transplant Unit, Great Ormond Street Hospital for Children, NHS Foundation Trust, London, UK and 2 Department of Hematological Medicine, Kings College Hospital, London, UK. Correspondence: Dr O Nikolajeva, Bone Marrow Transplant Unit, Great Ormond Street Hospital, Great Ormond Street, Level 5 Main Nurses Home, London WC1N 3JH, UK, E-mail: olganmd@gmail.com Received 14 July 2014; revised 11 February 2015; accepted 13 February 2015; published online 30 March 2015 Bone Marrow Transplantation (2015) 50, 846 – 849 © 2015 Macmillan Publishers Limited All rights reserved 0268-3369/15 www.nature.com/bmt