title: Suggestive evidence of a role of HLA-DRB4 mismatches in the outcome of allogeneic hematopoietic stem cell transplantation with HLA-10/10-matched unrelated donors: a French-Swiss retrospective study.
abstract: We have conducted a retrospective study on 251 patients from three centers in France and Switzerland between 2004 and 2010 with the goal to evaluate the impact of HLA-DRB3/B4/B5 allele mismatching after HLA-10/10-matched unrelated allogeneic hematopoietic stem cell transplantation (HSCT). Fourteen (5.5%) patients receiving HSCT from an HLA-10/10-matched unrelated donor had a mismatched DRB4 donor, 23 (9.5%) patients had a mismatched DRB3 donor and 214 (85%) had a fully matched unrelated donor (HLA-10/10) without DRB3- or DRB4-mismatched donor. We compared the outcomes of 37 patients with a DRB3 or DRB4 mismatch with the rest of the population. The median survival for a patient without DRB3/4 mismatch was 18 months (95% confidence interval (CI), 13-29), for DRB3-mismatched patients 32 months (95% CI, 13-NR) and for DRB4-mismatched patients 7 months (95% CI, 3-NR). The multivariate analysis showed a significant impact of DRB4 mismatching on survival (Hazards ratio (HR)=2.1 (95% CI, 1.01-4.67), P=0.045), acute GvHD (HR=2.66 (95% CI, 0.99-7.09) P=0.05) and on transplant-related mortality (HR=2.8; (95% CI, 1.7-4.4) P=0.024). In the view of an impact of DRB4 locus mismatch on clinical outcome, it would be important to confirm this observation in a prospective study as it may be worth considering DRB4 in the unrelated donor selection.
authors.affiliation: Department of Hematology, Groupement Hospitalier Sud, Hospices Civils de Lyon, Université Claude Bernard Lyon EST, Pierre Bénite, France.
authors.forename: M
authors.initials: M
authors.lastname: Detrait
authors.affiliation: Department of Hematology, Groupement Hospitalier Sud, Hospices Civils de Lyon, Université Claude Bernard Lyon EST, Pierre Bénite, France.
authors.forename: S
authors.initials: S
authors.lastname: Morisset
authors.affiliation: Hematology-Oncology and Bone Marrow Transplantation unit, Division of Hematology, Faculty of Medicine, Geneva University Hospital, University of Geneva, Geneva, Switzerland.
authors.forename: Y
authors.initials: Y
authors.lastname: Chalandon
authors.affiliation: Department of Hematology, Service des maladies du sang, CHR Lille, Lille, France.
authors.forename: I
authors.initials: I
authors.lastname: Yakoub-Agha
authors.affiliation: Laboratory for Histocompatibility, Etablissement Français du Sang, Lille, France.
authors.forename: F
authors.initials: F
authors.lastname: Dufossé
authors.affiliation: Laboratory for Histocompatibility, Etablissement Français du Sang, Lille, France.
authors.forename: M
authors.initials: M
authors.lastname: Labalette
authors.affiliation: Laboratory for Histocompatibility, Etablissement Français du Sang, Lille, France.
authors.forename: I
authors.initials: I
authors.lastname: Top
authors.affiliation: Laboratory for Histocompatibility, Etablissement Français du Sang, Lille, France.
authors.forename: V
authors.initials: V
authors.lastname: Elsermans
authors.affiliation: Department of Hematology, Groupement Hospitalier Sud, Hospices Civils de Lyon, Université Claude Bernard Lyon EST, Pierre Bénite, France.
authors.forename: F
authors.initials: F
authors.lastname: Barraco
authors.affiliation: Department of Hematology, Groupement Hospitalier Sud, Hospices Civils de Lyon, Université Claude Bernard Lyon EST, Pierre Bénite, France.
authors.forename: A
authors.initials: A
authors.lastname: Quintela
authors.affiliation: Department of Hematology, Groupement Hospitalier Sud, Hospices Civils de Lyon, Université Claude Bernard Lyon EST, Pierre Bénite, France.
authors.forename: N
authors.initials: N
authors.lastname: Tedone
authors.affiliation: Department of Hematology, Groupement Hospitalier Sud, Hospices Civils de Lyon, Université Claude Bernard Lyon EST, Pierre Bénite, France.
authors.forename: M
authors.initials: M
authors.lastname: Michallet
authors.affiliation: Société Française de Greffe de Moelle et de thérapie cellulaire, SFGM-TC Data Management, CHLS, pavillon Marcel Berard, Pierre Benite, France.
authors.forename: N
authors.initials: N
authors.lastname: Raus
authors.affiliation: Transplantation Immunology Unit, National Reference Laboratory for Histocompatibility, Geneva University Hospitals, University of Geneva, Geneva, Switzerland.
authors.forename: J-M
authors.initials: JM
authors.lastname: Tiercy
authors.affiliation: Transplantation Immunology Unit, Laboratory for Histocompatibility, Etablissement Français du Sang, Lyon, France.
authors.forename: V
authors.initials: V
authors.lastname: Dubois
mesh_terms: D005260:Female; D005602:France; D059845:HLA-DRB4 Chains / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006648:Histocompatibility / Q000276:immunology*; D006650:Histocompatibility Testing; D006801:Humans; D008297:Male; D012189:Retrospective Studies; D016019:Survival Analysis; D013557:Switzerland; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous / Q000379:methods*; D016896:Treatment Outcome; D061349:Unrelated Donors
chemical_list: D059845:HLA-DRB4 Chains