title: Alloreactivity: the Janus-face of hematopoietic stem cell transplantation.
abstract: Differences in major and minor histocompatibility antigens between donor and recipient trigger powerful graft-versus-host reactions after allogeneic hematopoietic stem cell transplantation (HSCT). The clinical effects of alloreactivity present a Janus-face: detrimental graft-versus-host disease increases non-relapse mortality, beneficial graft-versus-malignancy may cure the recipient. The ultimate consequences on long-term outcome remain a matter of debate. We hypothesized that increasing donor-recipient antigen matching would decrease the negative effects, while preserving antitumor alloreactivity. We analyzed retrospectively a predefined cohort of 32 838 such patients and compared it to 59 692 patients with autologous HSCT as reference group. We found a significant and systematic decrease in non-relapse mortality with decreasing phenotypic and genotypic antigen disparity, paralleled by a stepwise increase in overall and relapse-free survival (Spearman correlation coefficients of cumulative excess event rates at 5 years 0.964; P<0.00; respectively 0.976; P<0.00). We observed this systematic stepwise effect in all main disease and disease-stage categories. The results suggest that detrimental effects of alloreactivity are additive with each step of mismatching; the beneficial effects remain preserved. Hence, if there is a choice, the best match should be donor of choice. The data support an intensified search for predictive genomic and environmental factors of 'no-graft-versus-host disease'.
authors.affiliation: EBMT Activity Survey Office, University Hospital, Basel, Switzerland.
authors.forename: A
authors.initials: A
authors.lastname: Gratwohl
authors.affiliation: ICO Institute of Clinical Oncology, ICO-Hospital Duran i Reynals, L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Sureda
authors.affiliation: Hematology, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Cornelissen
authors.affiliation: Haematology, Hammersmith Hospital, London, UK.
authors.forename: J
authors.initials: J
authors.lastname: Apperley
authors.affiliation: Medical Clinic and Policlinic, University of Heidelberg, Heidelberg, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Dreger
authors.affiliation: Department of Hematology, University Hospital Puerta de Hierro Majadahonda, Madrid, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Duarte
authors.affiliation: Division of Hematology, Medical University of Graz, Graz, Austria.
authors.forename: H T
authors.initials: HT
authors.lastname: Greinix
authors.affiliation: JACIE Accreditation Office, Barcelona, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Mc Grath
authors.affiliation: Department of Stem Cell Transplantation, University Hospital Eppendorf, Hamburg, Germany.
authors.forename: N
authors.initials: N
authors.lastname: Kroeger
authors.affiliation: Unità Operativa di Ematologia, Ospedale Civile, Ravenna, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Lanza
authors.affiliation: Stem Cell Transplantation Unit, Chaim Sheba Medical Center, Tel-Hashomer, Israel.
authors.forename: A
authors.initials: A
authors.lastname: Nagler
authors.affiliation: Department of Haematology, Sheffield Teaching Hospitals NHS Foundation Trust, and Department of Oncology and Metabolism, University of Sheffield, Sheffield, UK.
authors.forename: J A
authors.initials: JA
authors.lastname: Snowden
authors.affiliation: Hematology and Oncology, University Hospital, Leipzig, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Niederwieser
authors.affiliation: Department of Medical Statistics and Bioinformatics, Leiden University Medical Centre, Leiden, The Netherlands.
authors.forename: R
authors.initials: R
authors.lastname: Brand
mesh_terms: D006086:Graft vs Host Disease / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation; D006650:Histocompatibility Testing; D006801:Humans; D012189:Retrospective Studies; D014184:Transplantation, Homologous