title: Treatment of hemophagocytic lymphohistiocytosis with HLH-94 immunochemotherapy and bone marrow transplantation.
abstract: Hemophagocytic lymphohistiocytosis (HLH) comprises familial (primary) hemophagocytic lymphohistiocytosis (FHL) and secondary HLH (SHLH), both clinically characterized by fever, hepatosplenomegaly, and cytopenia. FHL, an autosomal recessive disease invariably fatal when untreated, is associated with defective triggering of apoptosis and reduced cytotoxic activity, resulting in a widespread accumulation of T lymphocytes and activated macrophages. In 1994 the Histiocyte Society initiated a prospective international collaborative therapeutic study (HLH-94), aiming at improved survival. It combined chemotherapy and immunotherapy (etoposide, corticosteroids, cyclosporin A, and, in selected patients, intrathecal methotrexate), followed by bone marrow transplantation (BMT) in persistent, recurring, and/or familial disease. Between July 1, 1994, and June 30, 1998, 113 eligible patients aged no more than 15 years from 21 countries started HLH-94. All had either an affected sibling (n = 25) and/or fulfilled the Histiocyte Society diagnostic criteria. At a median follow-up of 3.1 years, the estimated 3-year probability of survival overall was 55% (95% confidence interval +/- 9%), and in the familial cases, 51% (+/- 20%). Twenty enrolled children were alive and off therapy for more than 12 months without BMT. For patients who received transplants (n = 65), died prior to BMT (n = 25), or were still on therapy (n = 3), the 3-year survival was 45% (+/- 10%). The 3-year probability of survival after BMT was 62% (+/- 12%). HLH-94 is very effective, allowing BMT in most patients. Survival of children with HLH has been greatly improved.
authors.affiliation: Childhood Cancer Research Unit, Karolinska Institutet, Department of Pediatric Hematology and Oncology, Karolinska Hospital, Stockholm, Sweden. Jan-Inge.Henter@kbh.ki.se
authors.forename: Jan-Inge
authors.initials: JI
authors.lastname: Henter
authors.forename: AnnaCarin
authors.initials: A
authors.lastname: Samuelsson-Horne
authors.forename: Maurizio
authors.initials: M
authors.lastname: Aricò
authors.forename: R Maarten
authors.initials: RM
authors.lastname: Egeler
authors.forename: Göran
authors.initials: G
authors.lastname: Elinder
authors.forename: Alexandra H
authors.initials: AH
authors.lastname: Filipovich
authors.forename: Helmut
authors.initials: H
authors.lastname: Gadner
authors.forename: Shinsaku
authors.initials: S
authors.lastname: Imashuku
authors.forename: Diane
authors.initials: D
authors.lastname: Komp
authors.forename: Stephan
authors.initials: S
authors.lastname: Ladisch
authors.forename: David
authors.initials: D
authors.lastname: Webb
authors.forename: Gritta
authors.initials: G
authors.lastname: Janka
mesh_terms: D000293:Adolescent; D017668:Age of Onset; D016026:Bone Marrow Transplantation; D002648:Child; D003561:Cytarabine / Q000627:therapeutic use; D003907:Dexamethasone / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005047:Etoposide / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D015616:Histiocytosis, Non-Langerhans-Cell / Q000188:drug therapy / Q000401:mortality / Q000628:therapy*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D008942:Mitoxantrone / Q000627:therapeutic use; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis; D013997:Time Factors
chemical_list: D007166:Immunosuppressive Agents; D003561:Cytarabine; D005047:Etoposide; D003907:Dexamethasone; D008942:Mitoxantrone