TY - JOUR
T1 - Antilymphocyte globulin for prevention of chronic graft-versus-host disease
AU - Kröger, Nicolaus
AU - Solano, Carlos
AU - Wolschke, Christine
AU - Bandini, Giuseppe
AU - Patriarca, Francesca
AU - Pini, Massimo
AU - Nagler, Arnon
AU - Selleri, Carmine
AU - Risitano, Antonio
AU - Messina, Giuseppe
AU - Bethge, Wolfgang
AU - De Oteiza, Jaime Pérez
AU - Duarte, Rafael
AU - Carella, Angelo Michele
AU - Cimminiello, Michele
AU - Guidi, Stefano
AU - Finke, Jürgen
AU - Mordini, Nicola
AU - Ferra, Christelle
AU - Sierra, Jorge
AU - Russo, Domenico
AU - Petrini, Mario
AU - Milone, Giuseppe
AU - Benedetti, Fabio
AU - Heinzelmann, Marion
AU - Pastore, Domenico
AU - Jurado, Manuel
AU - Terruzzi, Elisabetta
AU - Narni, Franco
AU - Völp, Andreas
AU - Ayuk, Francis
AU - Ruutu, Tapani
AU - Bonifazi, Francesca
N1 - Publisher Copyright:
Copyright © 2016 Massachusetts Medical Society.
PY - 2016/1/7
Y1 - 2016/1/7
N2 - 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 relapsefree survival was higher with ATG. (Funded by the Neovii Biotech and the European Society for Blood and Marrow Transplantation; ClinicalTrials.gov number, NCT00678275.
AB - 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 relapsefree survival was higher with ATG. (Funded by the Neovii Biotech and the European Society for Blood and Marrow Transplantation; ClinicalTrials.gov number, NCT00678275.
UR - http://www.scopus.com/inward/record.url?scp=84954064873&partnerID=8YFLogxK
U2 - 10.1056/NEJMoa1506002
DO - 10.1056/NEJMoa1506002
M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???
C2 - 26735993
AN - SCOPUS:84954064873
SN - 0028-4793
VL - 374
SP - 43
EP - 53
JO - New England Journal of Medicine
JF - New England Journal of Medicine
IS - 1
ER -