title: Antilymphocyte Globulin for Prevention of Chronic Graft-versus-Host Disease.
abstract: 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.).
authors.affiliation: From the University Medical Center Hamburg-Eppendorf, Hamburg (N.K., C.W., M.H., F.A.), University Hospital Freiburg, Freiburg (J.F.), University Hospital Tübingen, Tübingen (W.B.), and Psy Consult, Frankfurt (A.V.) - all in Germany; Hospital Clinico Universitario, Valencia (C. Solano), Hospital Ramon y Cajal (J.P.O.) and Hospital Universitario Puerta de Hierro Majadahonda (R.D.), Madrid, Servicio de Hematología, Institut Català d'Oncologia, Hospital Universitari Germans Trias i Pujol, Badalona, (C.F.), Hospital de la Santa Creu i Sant Pau, Barcelona (J.S.), and Hospital Virgen de las Nieves, Granada (M.J.) - all in Spain; S. Orsola-Malpighi University Hospital, University of Bologna, Bologna (G.B., F. Bonifazi), Hematology, DISM, University Udine, Udine (F.P.), Azienda Ospedaliera SS Antonio e Biagio e C. Arrigo, Alessandria (M. Pini), Università Federico II di Napoli, Naples (C. Selleri, A.R.), A.O. Bianchi-Melacrino-Morelli, Reggio Calabria (G. Messina), Ospedale Casa Sollievo della Sofferenza IRCCCS, San Giovanni Rotondo (A.M.C.), Azienda Ospedaliera San Carlo, Potenza (M.C.), Azienda Ospedaliera Careggi, Florence (S.G.), Ospedale Santa Croce, e Carle, Cuneo (N.M.), University of Brescia, Department of Clinical and Experimental Sciences, Brescia (D.R.), University of Pisa, Department of Clinical and Experimental Medicine, Pisa (M. Petrini), Programma di Trapianto Emopoietico Metropolitano, Azienda Policlinico-Vittorio Emanuele, Catania (G. Milone), Policlinico G.B. Rossi, Verona (F. Benedetti), Azienda Ospedaliera, Universitaria Ospedale, Bari (D.P.), Ospedale San Gerardo, Monza (E.T.), Policlinico Modena, Modena (F.N.), and Università di Salerno, Salerno (C. Selleri) - all in Italy; Chaim Sheba Medical Center, Tel Hashomer, Ramat-Gan, Israel (A.N.); and Helsinki University Hospital, Helsinki (T.R.).
authors.forename: Nicolaus
authors.initials: N
authors.lastname: Kröger
authors.forename: Carlos
authors.initials: C
authors.lastname: Solano
authors.forename: Christine
authors.initials: C
authors.lastname: Wolschke
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Bandini
authors.forename: Francesca
authors.initials: F
authors.lastname: Patriarca
authors.forename: Massimo
authors.initials: M
authors.lastname: Pini
authors.forename: Arnon
authors.initials: A
authors.lastname: Nagler
authors.forename: Carmine
authors.initials: C
authors.lastname: Selleri
authors.forename: Antonio
authors.initials: A
authors.lastname: Risitano
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Messina
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Bethge
authors.forename: Jaime
authors.initials: J
authors.lastname: Pérez de Oteiza
authors.forename: Rafael
authors.initials: R
authors.lastname: Duarte
authors.forename: Angelo Michele
authors.initials: AM
authors.lastname: Carella
authors.forename: Michele
authors.initials: M
authors.lastname: Cimminiello
authors.forename: Stefano
authors.initials: S
authors.lastname: Guidi
authors.forename: Jürgen
authors.initials: J
authors.lastname: Finke
authors.forename: Nicola
authors.initials: N
authors.lastname: Mordini
authors.forename: Christelle
authors.initials: C
authors.lastname: Ferra
authors.forename: Jorge
authors.initials: J
authors.lastname: Sierra
authors.forename: Domenico
authors.initials: D
authors.lastname: Russo
authors.forename: Mario
authors.initials: M
authors.lastname: Petrini
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Milone
authors.forename: Fabio
authors.initials: F
authors.lastname: Benedetti
authors.forename: Marion
authors.initials: M
authors.lastname: Heinzelmann
authors.forename: Domenico
authors.initials: D
authors.lastname: Pastore
authors.forename: Manuel
authors.initials: M
authors.lastname: Jurado
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Terruzzi
authors.forename: Franco
authors.initials: F
authors.lastname: Narni
authors.forename: Andreas
authors.initials: A
authors.lastname: Völp
authors.forename: Francis
authors.initials: F
authors.lastname: Ayuk
authors.forename: Tapani
authors.initials: T
authors.lastname: Ruutu
authors.forename: Francesca
authors.initials: F
authors.lastname: Bonifazi
mesh_terms: D000293:Adolescent; D000328:Adult; D000961:Antilymphocyte Serum / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D018572:Disease-Free Survival; D005260:Female; D006086:Graft vs Host Disease / Q000453:epidemiology / Q000401:mortality / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D015994:Incidence; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011446:Prospective Studies; D015996:Survival Rate; D013601:T-Lymphocytes / Q000276:immunology*; D014184:Transplantation, Homologous; D055815:Young Adult
chemical_list: D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents