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.

Keywords: Allogeneic stem cell transplantation; Antithymocyte globulin; Grades 3 to 4 hepatitis.