title: Transient grades 3 to 4 acute hepatitis is a common complication of rabbit antithymocyte globulin (thymoglobulin) administered before allogeneic stem cell transplantation.
abstract: Because antithymocyte globulin (ATG) is increasingly used to prevent graft-versus-host disease (GVHD), we performed a retrospective study in adult patients transplanted at our center between January 2008 and December 2012 to explore incidence, characteristics, potential risk factors, and consequences of severe acute hepatotoxicity (SAH) of rabbit ATG (Thymoglobulin) defined as a grade 3 to 4 increase of transaminases. Two hundred twelve patients were included. SAH was diagnosed in 55 patients, representing an incidence of 26%. SAH occurred at a median time of 2 days (range, 1 to 3) after ATG administration, reaching maximum median levels of aspartate aminotransferase and alanine aminotransferase of 8.7 × upper limit of normal (ULN; range, 1.2 to 160) and 11.7 × ULN (range, 4-100), respectively. The International Normalized Ratio was beyond the normal range in 44% of patients. Transaminases decreased below 2 × ULN after a median time of 9 days. We do not report any deleterious impact of SAH on survival, nonrelapse mortality, relapse, or GVHD. Blood systolic pressure < 90 mm Hg during administration of ATG and 2 previous autologous SCT were identified as risk factors for SAH. We believe physicians should be aware of this common toxicity immediately after the administration of ATG to avoid any potential hepatotoxic drug before the resolution and to prevent any risk of hemorrhagic accident.
authors.affiliation: Service d'Hématologie et de Thérapie Cellulaire, CHU Haut-Lévêque, Bordeaux, France.
authors.forename: Clémence
authors.initials: C
authors.lastname: Médiavilla
authors.affiliation: Service d'Hématologie et de Thérapie Cellulaire, CHU Haut-Lévêque, Bordeaux, France. Electronic address: stephane.vigouroux@chu-bordeaux.fr.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Vigouroux
authors.affiliation: Service d'Hématologie et de Thérapie Cellulaire, CHU Haut-Lévêque, Bordeaux, France.
authors.forename: Reza
authors.initials: R
authors.lastname: Tabrizi
authors.affiliation: Service d'Hématologie et de Thérapie Cellulaire, CHU Haut-Lévêque, Bordeaux, France; Université Bordeaux Segalen, Bordeaux, France.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Pigneux
authors.affiliation: Service d'Hématologie et de Thérapie Cellulaire, CHU Haut-Lévêque, Bordeaux, France.
authors.forename: Cédric
authors.initials: C
authors.lastname: Duclos
authors.affiliation: Service d'Hématologie et de Thérapie Cellulaire, CHU Haut-Lévêque, Bordeaux, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Mohr
authors.affiliation: Service d'Hématologie et de Thérapie Cellulaire, CHU Haut-Lévêque, Bordeaux, France.
authors.forename: Margot
authors.initials: M
authors.lastname: Robles
authors.affiliation: Service d'Hématologie et de Thérapie Cellulaire, CHU Haut-Lévêque, Bordeaux, France; Université Bordeaux Segalen, Bordeaux, France.
authors.forename: Noël
authors.initials: N
authors.lastname: Milpied
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D064591:Allografts; D000818:Animals; D000961:Antilymphocyte Serum / Q000008:administration & dosage*; D018572:Disease-Free Survival; D005260:Female; D006086:Graft vs Host Disease / Q000097:blood / Q000401:mortality / Q000517:prevention & control; D019337:Hematologic Neoplasms / Q000097:blood / Q000401:mortality / Q000628:therapy; D006505:Hepatitis / Q000097:blood / Q000401:mortality / Q000517:prevention & control; D006801:Humans; D008297:Male; D008875:Middle Aged; D011817:Rabbits; D012189:Retrospective Studies; D033581:Stem Cell Transplantation; D015996:Survival Rate
chemical_list: D000961:Antilymphocyte Serum; C512542:thymoglobulin
keywords: Allogeneic stem cell transplantation; Antithymocyte globulin; Grades 3 to 4 hepatitis