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Leukemia. 2017 Apr;31(4):903-912. doi: 10.1038/leu.2016.281. Epub 2016 Oct 14.

Pre-transplant donor CD4- invariant NKT cell expansion capacity predicts the occurrence of acute graft-versus-host disease.

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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.
Unité de Recherche Clinique, Paris Centre Necker Cochin, Hôpital Tarnier, Paris, France.
Département de Biothérapie, Groupe Hospitalier Pitié-Salpêtrière, Paris, France.
Service d'Hématologie Clinique, Assistance Publique-Hôpitaux de Paris, Hôpital Necker, Paris, France.
Therapeutic Apheresis Unit, Saint-Louis Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.
Service d'Hématologie, Groupe Hospitalier Pitié-Salpêtrière, Paris, France.
Biotherapy Department, Necker Children's Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.
INSERM U1163, Laboratory of Human Lymphohematopoiesis, Paris, France.
INSERM U932, Département de Biologie des Tumeurs, Institut Curie, Paris, France.
Centre d'Investigation Clinique, CICBT507 IGR/Curie, Paris, France.
INSERM CIC 1419, EAU08 Université Paris Descartes, Paris, France.


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.

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