title: Larger number of invariant natural killer T cells in PBSC allografts correlates with improved GVHD-free and progression-free survival.
abstract: We studied the impact of a set of immune cells contained within granulocyte colony-stimulating factor-mobilized peripheral blood stem cell grafts (naïve and memory T-cell subsets, B cells, regulatory T cells, invariant natural killer T cells [iNKTs], NK cells, and dendritic cell subsets) in patients (n = 80) undergoing allogeneic stem cell transplantation (SCT), using the composite end point of graft-versus-host disease (GVHD)-free and progression-free survival (GPFS) as the primary end point. We observed that GPFS incidences in patients receiving iNKT doses above and below the median were 49% vs 22%, respectively (P= .007). In multivariate analysis, the iNKT dose was the only parameter with a significant impact on GPFS (hazard ratio = 0.48; 95% confidence interval, 0.27-0.85;P= .01). The incidences of severe grade III to IV acute GVHD and National Institutes of Health grade 2 to 3 chronic GVHD (12% and 16%, respectively) were low and associated with the use of antithymocyte globulin in 91% of patients. No difference in GVHD incidence was reported according to the iNKT dose. In conclusion, a higher dose of iNKTs within the graft is associated with an improved GPFS. These data may pave the way for prospective and active interventions aiming to manipulate the graft content to improve allo-SCT outcome.
authors.affiliation: Service d'Hématologie Clinique, Centre Hospitalier Universitaire de Nantes, Nantes, France; Centre de Recherche Saint-Antoine, INSERM, Unité Mixte de Recherche (UMR) 938, Paris, France; Université Pierre et Marie Curie, Paris, France; INSERM, UMR1064-Center for Research in Transplantation and Immunology, Nantes, France; Service d'Hématologie Clinique et de Thérapie Cellulaire, Hôpital Saint Antoine, Assistance Publique-Hôpitaux de Paris, Paris, France;
authors.forename: Florent
authors.initials: F
authors.lastname: Malard
authors.affiliation: Centre de Recherche Saint-Antoine, INSERM, Unité Mixte de Recherche (UMR) 938, Paris, France; Université Pierre et Marie Curie, Paris, France; Service d'Hématologie Clinique et de Thérapie Cellulaire, Hôpital Saint Antoine, Assistance Publique-Hôpitaux de Paris, Paris, France;
authors.forename: Myriam
authors.initials: M
authors.lastname: Labopin
authors.affiliation: Service d'Hématologie Clinique, Centre Hospitalier Universitaire de Nantes, Nantes, France;
authors.forename: Patrice
authors.initials: P
authors.lastname: Chevallier
authors.affiliation: Service d'Hématologie Clinique, Centre Hospitalier Universitaire de Nantes, Nantes, France;
authors.forename: Thierry
authors.initials: T
authors.lastname: Guillaume
authors.affiliation: Etablissement Français du Sang (EFS) Pays-de-Loire, Nantes, France;
authors.forename: Alix
authors.initials: A
authors.lastname: Duquesne
authors.affiliation: Service d'Hématologie Clinique, Centre Hospitalier Universitaire de Nantes, Nantes, France;
authors.forename: Fanny
authors.initials: F
authors.lastname: Rialland
authors.affiliation: Etablissement Français du Sang (EFS) Pays-de-Loire, Nantes, France;
authors.forename: Sophie
authors.initials: S
authors.lastname: Derenne
authors.affiliation: Service d'Hématologie Clinique, Centre Hospitalier Universitaire de Nantes, Nantes, France;
authors.forename: Pierre
authors.initials: P
authors.lastname: Peterlin
authors.affiliation: Etablissement Français du Sang (EFS) Pays-de-Loire, Nantes, France;
authors.forename: Anne-Gaelle
authors.initials: AG
authors.lastname: Leauté
authors.affiliation: Centre de Recherche Saint-Antoine, INSERM, Unité Mixte de Recherche (UMR) 938, Paris, France; Université Pierre et Marie Curie, Paris, France; INSERM, UMR1064-Center for Research in Transplantation and Immunology, Nantes, France;
authors.forename: Eolia
authors.initials: E
authors.lastname: Brissot
authors.affiliation: INSERM Centre de Recherche en Cancérologie Nantes Angers UMR 892, Nantes, France; and.
authors.forename: Marc
authors.initials: M
authors.lastname: Gregoire
authors.affiliation: Service d'Hématologie Clinique, Centre Hospitalier Universitaire de Nantes, Nantes, France;
authors.forename: Philippe
authors.initials: P
authors.lastname: Moreau
authors.affiliation: INSERM UMR1098, Université de Franche-Comté and EFS Bourgogne Franche-Comté, Plateforme de BioMonitoring, UMR 1098, Besançon, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Saas
authors.affiliation: Centre de Recherche Saint-Antoine, INSERM, Unité Mixte de Recherche (UMR) 938, Paris, France; Université Pierre et Marie Curie, Paris, France;
authors.forename: Béatrice
authors.initials: B
authors.lastname: Gaugler
authors.affiliation: Centre de Recherche Saint-Antoine, INSERM, Unité Mixte de Recherche (UMR) 938, Paris, France; Université Pierre et Marie Curie, Paris, France; Service d'Hématologie Clinique et de Thérapie Cellulaire, Hôpital Saint Antoine, Assistance Publique-Hôpitaux de Paris, Paris, France;
authors.forename: Mohamad
authors.initials: M
authors.lastname: Mohty
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D064591:Allografts; D000961:Antilymphocyte Serum / Q000008:administration & dosage*; D002648:Child; D002908:Chronic Disease; D018572:Disease-Free Survival; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000517:prevention & control; D006801:Humans; D008297:Male; D008875:Middle Aged; D055611:Natural Killer T-Cells / Q000276:immunology* / Q000473:pathology*; D012189:Retrospective Studies; D033581:Stem Cell Transplantation; D015996:Survival Rate
chemical_list: D000961:Antilymphocyte Serum