title: Pre-transplant donor CD4-invariant NKT cell expansion capacity predicts the occurrence of acute graft-versus-host disease.
abstract: Clinically useful pre-transplant predictive factors of acute graft-versus-host-disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-SCT) are lacking. We prospectively analyzed HSC graft content in CD34+, NK, conventional T, regulatory T and invariant natural killer T (iNKT) cells in 117 adult patients before allo-SCT. Results were correlated with occurrence of aGVHD and relapse. In univariate analysis, iNKT cells were the only graft cell populations associated with occurrence of aGVHD. In multivariate analysis, CD4-iNKT/T cell frequency could predict grade II-IV aGVHD in bone marrow and peripheral blood stem cell (PBSC) grafts, while CD4-iNKT expansion capacity was predictive in PBSC grafts. Receiver operating characteristic analyses determined the CD4-iNKT expansion factor as the best predictive factor of aGVHD. Incidence of grade II-IV aGVHD was reduced in patients receiving a graft with an expansion factor above versus below 6.83 (9.7 vs 80%, P<0.0001), while relapse incidence at two years was similar (P=0.5).The test reached 94% sensitivity and 100% specificity in the subgroup of patients transplanted with human leukocyte antigen 10/10 PBSCs without active disease. Analysis of this CD4-iNKT expansion capacity test may represent the first diagnostic tool allowing selection of the best donor to avoid severe aGVHD with preserved graft-versus-leukemia effect after peripheral blood allo-SCT.
authors.affiliation: INSERM UMR 1163 and CNRS ERL 8254, Laboratory of Cellular and Molecular Mechanisms of Hemathological Disorders and Therapeutic Implication, Hôpital Necker, Paris, France.|Service d'Hématologie Clinique et de Thérapie Cellulaire, Assistance Publique-Hôpitaux de Paris, Hôpital Saint-Antoine, Paris, France.|INSERM UMRs 938, Centre de Recherche de l'hôpital Saint Antoine, Paris, France.|Université Pierre et Marie Curie, Paris VI, France.|Institut Hospitalo-Universitaire (IHU) Imagine, Paris Descartes-Sorbonne Paris Cité University, Paris, France.
authors.forename: M-T
authors.initials: MT
authors.lastname: Rubio
authors.affiliation: INSERM UMR 1163 and CNRS ERL 8254, Laboratory of Cellular and Molecular Mechanisms of Hemathological Disorders and Therapeutic Implication, Hôpital Necker, Paris, France.|Institut Hospitalo-Universitaire (IHU) Imagine, Paris Descartes-Sorbonne Paris Cité University, Paris, France.
authors.forename: M
authors.initials: M
authors.lastname: Bouillié
authors.affiliation: Unité de Recherche Clinique, Paris Centre Necker Cochin, Hôpital Tarnier, Paris, France.
authors.forename: N
authors.initials: N
authors.lastname: Bouazza
authors.affiliation: INSERM UMR 1163 and CNRS ERL 8254, Laboratory of Cellular and Molecular Mechanisms of Hemathological Disorders and Therapeutic Implication, Hôpital Necker, Paris, France.|Institut Hospitalo-Universitaire (IHU) Imagine, Paris Descartes-Sorbonne Paris Cité University, Paris, France.
authors.forename: T
authors.initials: T
authors.lastname: Coman
authors.affiliation: Département de Biothérapie, Groupe Hospitalier Pitié-Salpêtrière, Paris, France.
authors.forename: H
authors.initials: H
authors.lastname: Trebeden-Nègre
authors.affiliation: Service d'Hématologie Clinique et de Thérapie Cellulaire, Assistance Publique-Hôpitaux de Paris, Hôpital Saint-Antoine, Paris, France.|INSERM UMRs 938, Centre de Recherche de l'hôpital Saint Antoine, Paris, France.|Université Pierre et Marie Curie, Paris VI, France.
authors.forename: A
authors.initials: A
authors.lastname: Gomez
authors.affiliation: INSERM UMR 1163 and CNRS ERL 8254, Laboratory of Cellular and Molecular Mechanisms of Hemathological Disorders and Therapeutic Implication, Hôpital Necker, Paris, France.|Institut Hospitalo-Universitaire (IHU) Imagine, Paris Descartes-Sorbonne Paris Cité University, Paris, France.|Service d'Hématologie Clinique, Assistance Publique-Hôpitaux de Paris, Hôpital Necker, Paris, France.
authors.forename: F
authors.initials: F
authors.lastname: Suarez
authors.affiliation: INSERM UMR 1163 and CNRS ERL 8254, Laboratory of Cellular and Molecular Mechanisms of Hemathological Disorders and Therapeutic Implication, Hôpital Necker, Paris, France.|Service d'Hématologie Clinique, Assistance Publique-Hôpitaux de Paris, Hôpital Necker, Paris, France.
authors.forename: D
authors.initials: D
authors.lastname: Sibon
authors.affiliation: Therapeutic Apheresis Unit, Saint-Louis Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.
authors.forename: A
authors.initials: A
authors.lastname: Brignier
authors.affiliation: INSERM UMR 1163 and CNRS ERL 8254, Laboratory of Cellular and Molecular Mechanisms of Hemathological Disorders and Therapeutic Implication, Hôpital Necker, Paris, France.|Institut Hospitalo-Universitaire (IHU) Imagine, Paris Descartes-Sorbonne Paris Cité University, Paris, France.|Service d'Hématologie Clinique, Assistance Publique-Hôpitaux de Paris, Hôpital Necker, Paris, France.
authors.forename: E
authors.initials: E
authors.lastname: Paubelle
authors.affiliation: Service d'Hématologie, Groupe Hospitalier Pitié-Salpêtrière, Paris, France.
authors.forename: S
authors.initials: S
authors.lastname: Nguyen-Khoc
authors.affiliation: Institut Hospitalo-Universitaire (IHU) Imagine, Paris Descartes-Sorbonne Paris Cité University, Paris, France.|Biotherapy Department, Necker Children's Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.|INSERM U1163, Laboratory of Human Lymphohematopoiesis, Paris, France.
authors.forename: M
authors.initials: M
authors.lastname: Cavazzana
authors.affiliation: INSERM U932, Département de Biologie des Tumeurs, Institut Curie, Paris, France.|Centre d'Investigation Clinique, CICBT507 IGR/Curie, Paris, France.
authors.forename: O
authors.initials: O
authors.lastname: Lantz
authors.affiliation: Service d'Hématologie Clinique et de Thérapie Cellulaire, Assistance Publique-Hôpitaux de Paris, Hôpital Saint-Antoine, Paris, France.|INSERM UMRs 938, Centre de Recherche de l'hôpital Saint Antoine, Paris, France.|Université Pierre et Marie Curie, Paris VI, France.
authors.forename: M
authors.initials: M
authors.lastname: Mohty
authors.affiliation: Unité de Recherche Clinique, Paris Centre Necker Cochin, Hôpital Tarnier, Paris, France.|INSERM CIC 1419, EAU08 Université Paris Descartes, Paris, France.
authors.forename: S
authors.initials: S
authors.lastname: Urien
authors.affiliation: INSERM UMR 1163 and CNRS ERL 8254, Laboratory of Cellular and Molecular Mechanisms of Hemathological Disorders and Therapeutic Implication, Hôpital Necker, Paris, France.|Institut Hospitalo-Universitaire (IHU) Imagine, Paris Descartes-Sorbonne Paris Cité University, Paris, France.|Service d'Hématologie Clinique, Assistance Publique-Hôpitaux de Paris, Hôpital Necker, Paris, France.
authors.forename: O
authors.initials: O
authors.lastname: Hermine
mesh_terms: D000208:Acute Disease; D005260:Female; D006086:Graft vs Host Disease / Q000175:diagnosis / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D008297:Male; D055611:Natural Killer T-Cells / Q000276:immunology* / Q000378:metabolism; D057234:Preoperative Period; D011379:Prognosis; D012720:Severity of Illness Index; D014019:Tissue Donors; D014184:Transplantation, Homologous