The Safety and Efficacy of Granulocyte Transfusions in Pediatric Recipients with Severe Neutropenia

Abstract

Background:Pediatric oncology and stem cell transplant patients are at high risk for severe bacterial and fungal infections due to the myelosuppressive effects of chemotherapy and conditioning, respectively. Febrile neutropenia is one of the most concerning complications of chemotherapy. Even with the rapid initiation of empiric antibiotics, morbidity and mortality in this patient population occur frequently. Prognosis is worse in patients with proven bacteremia, with mortality rates of 18% and 5% reported in patients with gram‐negative and gram‐positive bacteremia, respectively (de Naurois et al. Annals of Oncology, 2010). Although gram positive organisms are known to be the most common cause of bacteremia in neutropenic patients (Kibbler et al. Curr Opin in Infect Dis, 1999), recent studies within the last 5 years have reported gram-negative organisms as the most common cause of bacteremia in this patient population (Mert et al. J Infect Dev Ctries, 2019, Islas-Muñoz et al. Int J Infect Dis, 2018, Sierra et al. Medicina, 2020, Cattaneo et al. Ann Hematol, 2018, Parodi et al. PloS one, 2019).Granulocytes harvested from healthy donors can temporarily raise the functional neutrophil counts in transfusion recipients. Data in the adult population show that while these transfusions are safe, they may be of limited efficacy, with patients receiving more than 6 x10 8 having better outcomes (Price et al. Blood, 2015). However, there is a paucity of data in the pediatric population (Atallah et al. Curr Opin in Hematol, 2006, Price et al. Semin Hematol, 2007, Estcourt et al. Cochrane Database Syst Rev, 2015).Objective:To determine the safety of granulocyte transfusions in pediatric recipients with severe neutropenia.Methods:Following IRB approval, we completed a retrospective cohort study of neutropenic pediatric recipients with various infections who received granulocyte transfusions. We reviewed the records of 74 pediatric recipients at the Maria Fareri Children's Hospital at Westchester Medical Center who received granulocyte transfusions from 2011-2019. The medical record was reviewed for patient age, underlying medical condition, indication for granulocyte transfusion, duration of fever, time to resolution of infection, mortality, and adverse reactions to the granulocyte transfusion. Mobilized granulocytes (dexamethasone) were collected from healthy donors at the New York Blood Center, as we have previously reported (Sulis/Cairo et al, Blood 2002, Price et al, Blood 2015).Results:The average age was 11 years (<1-20) with 38 male patients and 36 female patients. The majority of patients were either stem cell transplant recipients, patients with hematologic malignancies, or both. The most common indication for granulocyte transfusion was a documented bacterial infection (56.7%). Fifty-two percent had gram negative infection and 45.2% had gram positive infection. Nine percent were staph infections. Patients received granulocytes for a median of 7.5 days. 54% of the patients cleared their infection with antibiotics prior to receiving the granulocytes. In the remaining patients, infection resolved in 32.4% while receiving granulocyte transfusions in addition to antimicrobial therapy. In this subset of patients, 63.6% had bacterial infection with 71.4% having gram positive infection, all of which were staph infections. The infection cleared after a median of 4 days of granulocyte transfusions. Patients in this subset were on antibiotics for a median of 5 days prior to starting granulocytes. Adverse events related to the granulocyte infusion occurred in 6 patients, with 3 patients having a fever during the transfusion (CTCAE 1), 1 with hypothermia (CTCAE 2), and 1 with joint pain (CTCAE 1). 3 patients died during the period when they were receiving granulocytes. 2 due to infection complication and one due to seizure. 30 day survival was 86.5% and 100 day survival was 85.1%.Conclusions:Granulocyte transfusions can be safely administered to pediatric patients with severe neutropenia. 32.4% cleared the infection with granulocyte transfusion. 100 day survival is 85.1%. Adverse events had CTCAE scores of 1-2. A majority of patients had gram negative infections, but the majority of patients that had resolution of infection with granulocytes had staph infections. It is possible that granulocytes may have greater efficacy against staph infections than other types of infection. [Display omitted] DisclosuresLiu: Incyte: Honoraria; Pharmacyclics: Honoraria, Speakers Bureau; Astellas: Honoraria, Speakers Bureau; Pfizer: Research Funding; Beigene: Honoraria, Speakers Bureau; Celgene: Research Funding. Cairo: Jazz Pharmaceutical: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Speakers Bureau; Sanofi: Speakers Bureau; Servier: Speakers Bureau; Sobi: Speakers Bureau; Omeros: Membership on an entity's Board of Directors or advisory committees; Nektar: Membership on an entity's Board of Directors or advisory committees.