title: The diagnosis of adult-onset haemophagocytic lymphohistiocytosis: lessons learned from a review of 29 cases of bone marrow haemophagocytosis in two large academic institutions.
abstract: OBJECTIVE
  Haemophagocytic lymphohistiocytosis (HLH) is divided into paediatric (primary) and adult (secondary) types. While paediatric-HLH has been extensively characterised, similar studies in adults are limited. This study aims to evaluate the significance of the HLH diagnostic criteria as well as other clinical parameters in adults with bone marrow evidence of haemophagocytosis.
  
  
  METHODS
  We conducted a 10-year retrospective search of the pathology archives of two institutions for cases with bone marrow haemophagocytosis. We included those cases that fulfilled the currently established HLH diagnostic criteria. For the 29 cases that met inclusion criteria, we assessed clinical features, co-morbidities, therapy and clinical outcome. The effect of 19 clinical variables on mortality outcomes was assessed using logistic and hazard regression analyses.
  
  
  RESULTS
  Of cases for which an aetiology could be identified, infectious diseases were the most common association (14 of 19, 74%). Fever and elevated ferritin were the most frequently available criteria used to establish HLH. The overall mortality rate was 61% despite HLH-specific therapy, which had been initiated in 48% of the cases. The remaining cases were treated with supportive therapy and antibiotics. The most statistically significant marker of mortality was an elevated absolute neutrophil count (ANC), a feature not typical of HLH.
  
  
  CONCLUSIONS
  Since elevated ANC correlates with poor outcomes in sepsis, and not HLH, we postulate that many of the patients fulfilling HLH diagnostic criteria in this study likely had sepsis/systemic inflammatory response syndrome rather than HLH. Our results highlight the need to define HLH diagnostic criteria specific to the adult population.
authors.affiliation: Department of Pathology, West Virginia University, Morgantown, West Virginia, USA.
authors.forename: Flavia G
authors.initials: FG
authors.lastname: Rosado
authors.affiliation: Department of Pathology, Louisiana State University Health Sciences Center, New Orleans, Louisiana, USA.
authors.forename: Elizabeth B
authors.initials: EB
authors.lastname: Rinker
authors.affiliation: Department of Biostatistics, Vanderbilt University, Nashville, Tennessee, USA.
authors.forename: W D
authors.initials: WD
authors.lastname: Plummer
authors.affiliation: Department of Biostatistics, Vanderbilt University, Nashville, Tennessee, USA.
authors.forename: William D
authors.initials: WD
authors.lastname: Dupont
authors.affiliation: Department of Hematology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
authors.forename: Natalie M
authors.initials: NM
authors.lastname: Spradlin
authors.affiliation: Department of Pathology and Laboratory Medicine, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Kaaren K
authors.initials: KK
authors.lastname: Reichard
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Annette S
authors.initials: AS
authors.lastname: Kim
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001853:Bone Marrow / Q000473:pathology*; D005260:Female; D006801:Humans; D051359:Lymphohistiocytosis, Hemophagocytic / Q000175:diagnosis* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D055815:Young Adult
keywords: BONE MARROW; CLINICAL INFECTIOUS DISEASES; HEMATOPATHOLOGY; NEUTROPENIA