Lower dose anti-thymocyte globulin for GvHD prophylaxis results in improved survival after allogeneic stem cell transplantation

In vivo T-cell depletion with anti-thymocyte globulin (ATG) can attenuate GvHD but may increase infection and relapse risks. ATG-Fresenius (ATG-F) at a dose of 60 mg/kg was standard GvHD prophylaxis in unrelated donor hematopoietic stem cell transplantation (HSCT) at our institution. We changed to an incremental reduced dose regimen of 35 mg/kg and extended ATG prophylaxis to include older matched-related donor transplants considered to be at higher risk of GvHD. A total of 265 adults with hematological malignancies receiving a first allogeneic HSCT after myeloablative conditioning between 2009 and 2014 were analyzed in this cohort study. Patients had either received higher dose (n=32) or lower dose ATG-F (n=88) or no ATG (n=145). ATG-F was associated with slower engraftment and less chronic GvHD, whereas no effect was noted on acute grade II-IV GvHD and relapse incidence. Transplant-related mortality (TRM) was lower and survival higher with lower dose, but not with higher dose ATG-F. Both ATG-F groups were associated with more viral reactivation, viral disease and bacterial blood stream infection, but not invasive fungal infection, and with slower immune reconstitution. The recently adopted strategy of using lower doses of ATG-F in unrelated and older age-related donor HSCT appears to reduce TRM without increasing disease relapse, leading to slightly enhanced survival.