Posttransplant cyclophosphamide versus antithymocyte globulin in patients with acute lymphoblastic leukemia treated with allogeneic hematopoietic cell transplantation from matched unrelated donors: A study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation

Abstract

BackgroundThe aim of this study was to compare two immunosuppressive strategies, based on the use of either rabbit antithymocyte globulin (ATG) or posttransplant cyclophosphamide (PTCY), as a prophylaxis of graft‐versus‐host disease (GVHD) for patients with acute lymphoblastic leukemia (ALL) in first complete remission who underwent hematopoietic cells transplantation from matched unrelated donors.MethodsOverall, 117 and 779 adult patients who received PTCY and ATG, respectively, between the years 2015 and 2020 were included in this retrospective study. The median patient age was 40 and 43 years in the PTCY and ATG groups, respectively, and 37% and 35% of patients, respectively, had Philadelphia chromosome‐positive ALL.ResultsIn univariate analysis, the cumulative incidence of acute and chronic GVHD did not differ significantly between the study groups. The cumulative incidence of relapse at 2 years was reduced in the PTCY group (18% vs. 25%; p = .046) without a significant impact on nonrelapse mortality (11% vs. 16% in the ATG group; p = .29). The rates of leukemia‐free survival (LFS) and overall survival were 71% versus 59%, respectively (p = .01), and 82% versus 74%, respectively (p = .08). In multivariate analysis, the receipt of ATG compared with PTCY was associated with a reduced risk of extensive chronic GVHD (hazard ratio, 0.54; 95% confidence interval, 0.3–0.98; p = .04) and an increased risk of low LFS (hazard ratio, 1.57; 95% confidence interval, 1.01–2.45; p = .045).ConclusionsThe receipt of ATG compared with PTCY, despite the reduced risk of extensive chronic GVHD, is associated with inferior LFS in adults with ALL who undergo hematopoietic cell transplantation from 10/10 human leukocyte antigen‐matched unrelated donors. These findings warrant verification in prospective trials.

Post-Transplant Cyclophosphamide versus Anti-Thymocyte Globulin in Patients with Hematological Malignancies Treated with Allogeneic Hematopoietic Stem Cell Transplantation from Haploidentical and Matched Unrelated Donors: A Real-Life Experience

“…Moreover, GvHD occurrence after PTCY was not different than that reported in the ATG group, regardless of underlying hematological malignancies-not only ALL-and type of HSCT donor, as the majority of our patients received HSCT from a haploidentical donor. However, Giebel et al have described a reduced risk of extensive chronic GvHD in ATG recipients by a multivariate analysis (hazard ratio, 0.54; 95%CI, 0.3-0.98; p = 0.04) [1], not observed in our cohort. Although GvHD incidence was comparable between groups, we observed a significant protection from hematological relapse in the PTCY arm, likely because of a prompter T cell compartment and anti-tumor immune surveillance reconstitution [23].…”

“…Giebel et al have reported a lower cumulative incidence of relapse at 2 years (18% vs. 25%; p = 0.046), of leukemia-free survival rates (71% vs. 59%; p = 0.01), and of OS in the PTCY group (82% vs. 74%; p = 0.08) compared to ATG [ 1 ]. In our real-life study including different types of hematological malignancies, a significant protection from relapse was confirmed in PTCY-treated patients.…”

“…Allogenic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative therapeutic strategy for several benign and neoplastic hematological disorders; however, acute and chronic graft versus host disease (GvHD) is the principal post-transplant cause of death, leading to multi-organ failure [ 1 ]. This complication is driven by an immune attack against recipient tissue promoted by the donor’s lymphocytes; thus, HLA matching is the main risk factor of GvHD development and severity, as GvHD incidence in HLA-matched–related donor (MRD) HSCT is >30% [ 2 ].…”

Anti-T-lymphocyte globulin (ATLG) compared to post-transplant cyclophosphamide as GvHD prophylaxis in ALL patients undergoing allogeneic stem cell transplantation

“…Moreover, in the PTCy cohort the authors observed improved LFS and OS [26]. Another study recently published by EBMT observed a reduced risk for extensive chronic GvHD and an inferior LFS as compared to the PTCy group in ALL patients receiving ATG and undergoing hematopoietic cell transplantation from a MUD [25]. For the whole cohort our results are in line with those of EBMT with no differences in overall survival or in the incidence of acute GvHD, but with a significantly higher incidence of chronic GvHD in the PTCy group as compared to ATG.…”

“…Aydin et al compared ATG versus PTCy in matched unrelated donors in a non-myeloablative conditioning setting with similar outcomes in both groups [24]. A comparison of PTCy versus ATLG in a considerable ALL cohort in terms of outcome is scarcely to be found in the literature [25,26]. Therefore, we aimed to compare PTCy and ATLG as GvHD prophylaxis in ALL patients who received a TBI containing conditioning regimen in terms of leukemia-free and overall survival, transplant-related mortality, relapse incidence and incidence of acute and chronic GvHD.…”