Impact of antithymocyte globulin on outcomes of allogeneic hematopoietic cell transplantation with TBI

Abstract

The impact of the use of antithymocyte globulin (ATG) following a total body irradiation (TBI)–based myeloablative conditioning regimen has been poorly explored. We retrospectively analyzed 724 patients who underwent a first allogeneic hematopoietic cell transplantation (allo-HCT) following a TBI-based conditioning regimen for acute myeloid leukemia (AML) and compared the outcomes of 251 (35%) patients who received ATG (ATG group) with 473 (65%) patients who did not (non-ATG group). Median follow-up of surviving patients was 59 months (interquartile range, 28-83). The cumulative incidence of grade II-IV acute graft-versus-host disease (aGVHD) for non-ATG and ATG groups in the first 100 days was 33% vs 24%, respectively (P = .0098). The 2-year cumulative incidence of chronic graft-versus-host disease (cGVHD) was reduced significantly in the ATG group in comparison with the non-ATG group (46% vs 34%, P = .003). Using multivariate analysis, in vivo T-cell depletion (ATG group) was independently associated with a decreased incidence of grade II-IV aGVHD (hazard ratio [HR], 0.28; P < .001), grade III-IV aGVHD (HR, 0.21; P < .001), cGVHD (HR, 0.63; P = .02), and nonrelapse mortality (NRM) (HR, 0.54; P = .02). Relapse risk, overall survival, and leukemia-free survival were similar between the 2 groups. Our results suggest that the addition of ATG to TBI-based myeloablative conditioning for allo-HCT in AML patients results in a significant reduction in aGVHD and cGVHD, translating into a significant reduction in NRM without increasing the relapse rate.

Antithymocyte Globulin for Matched Sibling Donor Transplantation in Patients With Hematologic Malignancies: A Multicenter, Open-Label, Randomized Controlled Study

“…In addition, the results from retrospective studies in the CsA era are conflicting. [17][18][19][20][21] Therefore, the question of whether ATG/ATLG has the potential to prevent aGVHD in the era of CsA has been raised.…”

Impact of anti-thymocyte globulin dose for graft-versus-host disease prophylaxis in allogeneic hematopoietic cell transplantation from matched unrelated donors: a multicenter experience

“…The impact of ATG on clinical outcomes might also be affected by the intensity of conditioning regimen [ 44 , 45 ]. The role of ATG in RIC regimens remains to be determined, as only one randomized trial included RIC transplants and conflicting results were reported in retrospective studies [ 36 , 39 ].…”

Rabbit ATG/ATLG in preventing graft-versus-host disease after allogeneic stem cell transplantation: consensus-based recommendations by an international expert panel

“…Similarly, a dose-dependent relationship can be found with the speed of immune reconstitution. Relapse is increased only in one [16] of the randomized studies [12-15, 17, 38], in a particular subset of patients receiving a TBI-based conditioning regimen, but a retrospective analysis of the Acute Leukemia Working Party of the EBMT [76] did not confirm this finding. Advanced phase at transplant is a well-recognized risk factor for poorer survival, in particular for relapse, independently of ATLG infusion [26].…”