Kröger, NicolausSolano, CarlosWolschke, ChristineBandini, GiuseppePatriarca, FrancescaPini, MassimoNagler, ArnonSelleri, CarmineRisitano, AntonioMessina, GiuseppeBethge, WolfgangPérez de Oteiza, JaimeDuarte, RafaelCarella, Angelo MicheleCimminiello, MicheleGuidi, StefanoFinke, JürgenMordini, NicolaFerra, ChristelleSierra, JorgeRusso, DomenicoPetrini, MarioMilone, GiuseppeBenedetti, FabioHeinzelmann, MarionPastore, DomenicoJurado, ManuelTerruzzi, ElisabettaNarni, FrancoVölp, AndreasAyuk, FrancisRuutu, TapaniBonifazi, Francesca2016-08-292016-08-292016-01-07Kröger N, Solano C, Wolschke C, Bandini G, Patriarca F, Pini M, et al. Antilymphocyte Globulin for Prevention of Chronic Graft-versus-Host Disease. N. Engl. J. Med.. 2016 ; 374(1):43-530028-4793http://hdl.handle.net/10668/2373Clinical Trial, Phase III; Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't;BACKGROUND Chronic graft-versus-host disease (GVHD) is the leading cause of later illness and death after allogeneic hematopoietic stem-cell transplantation. We hypothesized that the inclusion of antihuman T-lymphocyte immune globulin (ATG) in a myeloablative conditioning regimen for patients with acute leukemia would result in a significant reduction in chronic GVHD 2 years after allogeneic peripheral-blood stem-cell transplantation from an HLA-identical sibling. METHODS We conducted a prospective, multicenter, open-label, randomized phase 3 study of ATG as part of a conditioning regimen. A total of 168 patients were enrolled at 27 centers. Patients were randomly assigned in a 1:1 ratio to receive ATG or not receive ATG, with stratification according to center and risk of disease. RESULTS After a median follow-up of 24 months, the cumulative incidence of chronic GVHD was 32.2% (95% confidence interval [CI], 22.1 to 46.7) in the ATG group and 68.7% (95% CI, 58.4 to 80.7) in the non-ATG group (P<0.001). The rate of 2-year relapse-free survival was similar in the ATG group and the non-ATG group (59.4% [95% CI, 47.8 to 69.2] and 64.6% [95% CI, 50.9 to 75.3], respectively; P=0.21), as was the rate of overall survival (74.1% [95% CI, 62.7 to 82.5] and 77.9% [95% CI, 66.1 to 86.1], respectively; P=0.46). There were no significant between-group differences in the rates of relapse, infectious complications, acute GVHD, or adverse events. The rate of a composite end point of chronic GVHD-free and relapse-free survival at 2 years was significantly higher in the ATG group than in the non-ATG group (36.6% vs. 16.8%, P=0.005). CONCLUSIONS The inclusion of ATG resulted in a significantly lower rate of chronic GVHD after allogeneic transplantation than the rate without ATG. The survival rate was similar in the two groups, but the rate of a composite end point of chronic GVHD-free survival and relapse-free survival was higher with ATG. (Funded by the Neovii Biotech and the European Society for Blood and Marrow Transplantation; ClinicalTrials.gov number, NCT00678275.).enSuero antilinfocíticoEnfermedad crónicaSupervivencia sin enfermedadEnfermedad injerto contra huéspedHumanosInmunosupresoresModelos de riesgos proporcionalesEstudios prospectivosLinfocitos tTrasplante homólogoMedical Subject Headings::Named Groups::Persons::Age Groups::AdultMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Blood Proteins::Immunoproteins::Immunoglobulins::Antibodies::Immune Sera::Antilymphocyte SerumMedical Subject Headings::Named Groups::Persons::Age Groups::ChildMedical Subject Headings::Named Groups::Persons::Age Groups::Child::Child, PreschoolMedical Subject Headings::Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Disease Attributes::Chronic DiseaseMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Prognosis::Disease-Free SurvivalMedical Subject Headings::Check Tags::FemaleMedical Subject Headings::Diseases::Immune System Diseases::Graft vs Host DiseaseMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::HumansMedical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Physiological Effects of Drugs::Immunologic Factors::Immunosuppressive AgentsMedical Subject Headings::Named Groups::Persons::Age Groups::Adult::Middle AgedMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Models, Statistical::Proportional Hazards ModelsMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Longitudinal Studies::Prospective StudiesMedical Subject Headings::Anatomy::Cells::Blood Cells::Leukocytes::Leukocytes, Mononuclear::Lymphocytes::T-LymphocytesMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Surgical Procedures, Operative::Transplantation::Transplantation, HomologousMedical Subject Headings::Named Groups::Persons::Age Groups::Adult::Young AdultMedical Subject Headings::Named Groups::Persons::Age Groups::Adolescentresearch article26735993open access10.1056/NEJMoa15060021533-4406