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

Abstract

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.

Impact of in vivo T cell depletion in HLA-identical allogeneic stem cell transplantation for acute myeloid leukemia in first complete remission conditioned with a fludarabine iv-busulfan myeloablative regimen: a report from the EBMT Acute Leukemia Working Party

“…The current study was limited to AML in CR1 transplanted with HLA-identical donors to reduce bias due to donor type and disease status on transplant outcomes. As reported in other contexts of allo-SCT [14, 16, 17, 27–30], we confirm in the present study that the addition of intermediate dose of thymoglobulin (median, 5 mg/kg) significantly reduces, after adjustment to other factors, the risk of developing cGVHD (Cox HR = 0.46, p  = 0.0001). Compared to patients not receiving ATG, those transplanted with ATG, despite having received more frequently PBSC, had a reduction of 2 years of cumulative incidence of the overall cGVHD from 52 to 31% ( p  = 0.00026) and that of extensive cGVHD from 26 to 8% ( p  < 10 −4 ).…”

“…Most patients had received a thymoglobulin dose of <6 mg/kg, so we could not analyze the impact of the ATG dose on outcomes. However, these results are in line with preserved GVL effect despite the addition of low or intermediate doses of ATG in the context of allo-SCT for AML performed with MRD and MUD following conventional MAC [31, 32] and RIC [29, 30, 33, 34], in contrast with increased risk of relapse with doses of thymoglobulin >10 mg/kg [28]. …”

Anti-thymocyte globulin as graft- versus -host disease prevention in the setting of allogeneic peripheral blood stem cell transplantation: a review from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation

“…A number of phase II studies have assessed the impact of rabbit ATG in patients given unmodified grafts after myeloablative conditioning [46][47][48][49][50][51][52] (Table 2). Collectively, these studies suggested that ATG decreased the incidence of grade III-IV acute and chronic GVHD without increasing non-relapse mortality (some studies even found lower non-relapse mortality with ATG), increased the incidence of post-transplantation lymphoproliferative disorders, and improved quality of life.…”

Post-transplant cyclophosphamide versus anti-thymocyte globulin as graft- versus -host disease prophylaxis in haploidentical transplant

“…Secondary end points were acute GvHD (aGvHD) and chronic GvHD (cGvHD), relapse incidence (RI), non-relapse mortality (NRM), GvHD-free, relapse-free survival (GRFS) 20,21 and overall survival (OS). Refined GRFS was defined as survival without the following events: grade 3-4 acute GvHD, severe cGvHD, disease relapse, or death from any cause after Haplo-SCT.…”