title: Severe neutropenia in children after renal transplantation: incidence, course, and treatment with granulocyte colony-stimulating factor.
abstract: BACKGROUND
  Infections are an important cause of morbidity and mortality in solid organ transplant recipients. Neutrophils play a crucial role in the initial host defense against bacterial pathogens. Neutropenia is not uncommon after renal transplantation in adults; however, there are scarce published data in children. We conducted a historical cohort study to evaluate the incidence, clinical course, and management of severe neutropenia after renal transplantation in children.
  
  
  METHODS
  In a single-center study, we collected clinical and laboratory data on all children (<20 years) who underwent renal transplantation from January 2005 to March 2014. All post-transplantation blood counts were reviewed; the lowest absolute neutrophil count was recorded and correlated with clinical information and other laboratory findings.
  
  
  RESULTS
  Of the 72 patients studied, 46 (64%) had at least one episode of neutropenia [absolute neutrophil count (ANC) <1500/μl] during the study period, 16 of whom (22%) had severe neutropenia (ANC < 500/μl), 2-11 months (median, 3.5) after renal transplantation. Work-up for viral infection or malignancy was performed. Initial management included dose decrease and subsequent discontinuation of antimetabolite, stopping co-trimoxazole and valganciclovir. Bone marrow aspiration in four children revealed normal marrow cellularity in all cases, with myelocyte maturational arrest in two. Eight children (11%) were treated with granulocyte colony-stimulating factor (G-CSF) (5 mcg/kg/day) 1-4 doses (median, 2), with excellent response in all and no adverse effects. Eight children presented with fever during severe neutropenia, and were treated with empiric antibiotics. Mycophenolate/azathioprine were resumed in all patients unless contraindicated (pre-existing BK viremia -1, PTLD -1). Recurrence of neutropenia was seen in five patients, only one of whom required further treatment with G-CSF. Graft function was preserved during and after resolution of neutropenia. Post-transplant neutropenia in children is common, and mostly occurs in the first few months. Its etiology is probably primarily a result of the combination of immunosuppressive agents and prophylactic treatment of infections in the early post-transplant period.
  
  
  CONCLUSIONS
  Decreasing immunosuppressive or antimicrobial medications carries the risk of acute rejection or infection. Off-label treatment with G-CSF may present a safe and effective alternative.
authors.affiliation: Division of Pediatric Nephrology, Shaare Zedek Medical Center, Jerusalem, Israel. rbeckercohen@yahoo.com.
authors.forename: Rachel
authors.initials: R
authors.lastname: Becker-Cohen
authors.affiliation: Division of Pediatric Nephrology, Shaare Zedek Medical Center, Jerusalem, Israel.
authors.forename: Efrat
authors.initials: E
authors.lastname: Ben-Shalom
authors.affiliation: Division of Pediatric Nephrology, Shaare Zedek Medical Center, Jerusalem, Israel.
authors.forename: Choni
authors.initials: C
authors.lastname: Rinat
authors.affiliation: Division of Pediatric Nephrology, Shaare Zedek Medical Center, Jerusalem, Israel.
authors.forename: Sofia
authors.initials: S
authors.lastname: Feinstein
authors.affiliation: Division of Pediatric Nephrology, Shaare Zedek Medical Center, Jerusalem, Israel.
authors.forename: Michael
authors.initials: M
authors.lastname: Geylis
authors.affiliation: Division of Pediatric Nephrology, Shaare Zedek Medical Center, Jerusalem, Israel.
authors.forename: Yaacov
authors.initials: Y
authors.lastname: Frishberg
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D006801:Humans; D016867:Immunocompromised Host; D015994:Incidence; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D009503:Neutropenia / Q000188:drug therapy* / Q000453:epidemiology* / Q000276:immunology
chemical_list: D016179:Granulocyte Colony-Stimulating Factor
keywords: Kidney transplantation; Mycophenolate; Neutropenia; Pediatric; Valganciclovir