title: Experience with hemophagocytic lymphohistiocytosis/macrophage activation syndrome at a single institution.
abstract: BACKGROUND
  Hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS) is a serious and potentially life threatening histiocytic disorder in children and adults. The most commonly used protocol-based therapy includes corticosteroids, cyclosporine-A, and etoposide. However, patients are often started on corticosteroid alone with or without the addition of intravenous gamma-globulin. The role of the various therapies in HLH/MAS remains undefined.
  
  
  OBJECTIVE
  To identify patient-related factors that led to the use of full protocol therapy (HLH 1994/2004) and to determine treatment-related factors that were associated with adverse outcome including relapse and death.
  
  
  METHODS
  Patients who were diagnosed with HLH/MAS between January 1998 and December 2005 were included in this study.
  
  
  RESULTS
  Thirty-eight patients had a median age of 9.1 years at diagnosis. Underlying diagnoses were: viral/other 42%; rheumatologic 37%; and malignancy 21%. Initial treatment included corticosteroids 29%; intravenous immunoglobulin (IVIG) 18%; steroids+IVIG 8%; cyclosporine 5%; etoposide 5%; HLH protocol 32%. Etoposide was eventually used in 21% (3/14) of rheumatology and 75% (18/25) viral/other patients. In all, 5/14 (36%) rheumatology and 12/16 (75%) viral/other patients required intensive care unit admission, and 1/14 (7.1%) rheumatology, and 6/16 (38%) viral/other patients died. Three children received a bone marrow transplant. Eleven of 38 (29%) patients died, despite 8 having received etoposide therapy. Three deaths were secondary to underlying malignancy and one from transplant-related complication for malignancy.
  
  
  CONCLUSIONS
  Patients with HLH are at high risk for death early in their disease course. However, corticosteroids and/or IVIG may be sufficient as first-line therapy for patients with underlying rheumatologic disease who present with HLH/MAS. Further prospective studies are required to more precisely define early risk factors for poor outcomes in this often fatal disease.
authors.affiliation: Division of Hematology/Oncology, Hospital for Sick Children, Toronto, Ontario, Canada. abha.gupta@sickkids.ca
authors.forename: Abha A
authors.initials: AA
authors.lastname: Gupta
authors.forename: Pascal
authors.initials: P
authors.lastname: Tyrrell
authors.forename: Rahim
authors.initials: R
authors.lastname: Valani
authors.forename: Susanne
authors.initials: S
authors.lastname: Benseler
authors.forename: Mohamed
authors.initials: M
authors.lastname: Abdelhaleem
authors.forename: Sheila
authors.initials: S
authors.lastname: Weitzman
mesh_terms: D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D002423:Cause of Death; D002648:Child; D002675:Child, Preschool; D016572:Cyclosporine / Q000627:therapeutic use; D005047:Etoposide / Q000627:therapeutic use; D005260:Female; D019337:Hematologic Neoplasms / Q000150:complications; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use; D007223:Infant; D051359:Lymphohistiocytosis, Hemophagocytic / Q000175:diagnosis / Q000188:drug therapy / Q000401:mortality; D055501:Macrophage Activation Syndrome / Q000175:diagnosis / Q000188:drug therapy / Q000401:mortality; D008297:Male; D012189:Retrospective Studies; D012216:Rheumatic Diseases / Q000150:complications; D013256:Steroids / Q000627:therapeutic use; D014777:Virus Diseases / Q000150:complications
chemical_list: D000305:Adrenal Cortex Hormones; D016756:Immunoglobulins, Intravenous; D013256:Steroids; D005047:Etoposide; D016572:Cyclosporine