title: Subtyping of natural killer cell cytotoxicity deficiencies in haemophagocytic lymphohistocytosis provides therapeutic guidance.
abstract: The familial form of haemophagocytic lymphohistiocytosis (HLH) is a fatal disease, with allogeneic stem cell transplantation (SCT) being the only curative treatment. In contrast, patients with secondary (infection-associated) HLH usually do not require SCT. Since it often is difficult to distinguish primary and secondary HLH, we wanted to identify a tool that provides guidance on whether SCT is required. The clinical outcome of 65 HLH patients was analysed in relation to the recently reported four types of defects in natural killer (NK)-cell cytotoxicity in HLH. None (0%) of the 36 patients with NK-cell deficiency type 3 attained a sustained (1-year) remission after stopping therapy without receiving SCT, in contrast to 45% (13/29) non-type 3 patients (P < 0.001). Most type 3 patients (22/36) underwent SCT (14/22, 64% are alive), whereas 11 of 14 that did not receive SCT died, and the three others had received HLH-therapy during the last year of follow-up. Of 54 patients analysed for perforin expression and/or mutation, the five with perforin deficiency were all type 3 patients. The data suggests that HLH patients with NK-cell deficiency type 3 will probably require SCT to survive. Thus, NK-cell deficiency classification may provide valuable guidance in judging whether an HLH-patient needs SCT.
authors.affiliation: Childhood Cancer Research Unit, Department of Paediatric Haematology and Oncology, Karolinska Hospital, Department of Woman and Child Health, Karolinska Institutet, Stockholm, Sweden.
authors.forename: AnnaCarin
authors.initials: A
authors.lastname: Horne
authors.forename: Chengyun
authors.initials: C
authors.lastname: Zheng
authors.forename: Ingrid
authors.initials: I
authors.lastname: Lorenz
authors.forename: Martina
authors.initials: M
authors.lastname: Löfstedt
authors.forename: Scott M
authors.initials: SM
authors.lastname: Montgomery
authors.forename: Gritta
authors.initials: G
authors.lastname: Janka
authors.forename: Jan-Inge
authors.initials: JI
authors.lastname: Henter
authors.forename: E
authors.initials: E
authors.lastname: Marion Schneider
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D003602:Cytotoxicity, Immunologic; D005260:Female; D015616:Histiocytosis, Non-Langerhans-Cell / Q000276:immunology* / Q000401:mortality / Q000601:surgery*; D006801:Humans; D007223:Infant; D007694:Killer Cells, Natural / Q000276:immunology*; D008297:Male; D018579:Patient Selection; D012074:Remission Induction; D018709:Statistics, Nonparametric; D033581:Stem Cell Transplantation; D015996:Survival Rate