Abstract
BackgroundGraft-versus-host disease (GVHD) is one of the leading causes of non-relapse mortality and morbidity after allogeneic hematopoietic stem cell transplantation (allo-HCT).MethodsWe evaluated the outcomes of two well-established strategies used for GVHD prevention: in vivo T cell depletion using antithymocyte globulin (ATG) and ex vivo T cell depletion using a CD34-selected (CD34+) graft. A total of 525 adult patients (363 ATG, 162 CD34+) with intermediate or high-risk cytogenetics acute myeloid leukemia (AML) in first complete remission (CR1) were included. Patients underwent myeloablative allo-HCT using matched related or unrelated donors.ResultsTwo-year overall survival estimate was 69.9% (95% CI, 58.5–69.4) in the ATG group and 67.6% (95% CI, 60.3–74.9) in the CD34+ group (p = 0.31). The cumulative incidence of grade II–IV acute GVHD and chronic GVHD was higher in the ATG cohort [HR 2.0 (95% CI 1.1–3.7), p = 0.02; HR 15.1 (95% CI 5.3–42.2), p < 0.0001]. Parameters associated with a lower GVHD-free relapse-free survival (GRFS) were ATG [HR 1.6 (95% CI 1.1–2.2), p = 0.006], adverse cytogenetic [HR 1.7 (95% CI 1.3–2.2), p = 0.0004], and the use of an unrelated donor [HR 1.4 (95% CI 1.0–1.9), p = 0.02]. There were no statistical differences between ATG and CD34+ in terms of relapse [HR 1.52 (95% CI 0.96–2.42), p = 0.07], non-relapse mortality [HR 0.96 (95% CI 0.54–1.74), p = 0.90], overall survival [HR 1.43 (95% CI 0.97–2.11), p = 0.07], and leukemia-free survival [HR 1.25 (95% CI 0.88–1.78), p = 0.21]. Significantly, more deaths related to infection occurred in the CD34+ group (16/52 vs. 19/112, p = 0.04).ConclusionsThese data suggest that both ex vivo CD34-selected and in vivo ATG T cell depletion are associated with a rather high OS and should be compared in a prospective randomized trial.
Highlights
Graft-versus-host disease (GVHD) is one of the leading causes of non-relapse mortality and morbidity after allogeneic hematopoietic stem cell transplantation
To compare the efficacy of both approaches, we retrospectively evaluated the outcomes of patients with intermediate or high-risk acute myeloid leukemia (AML) in first complete remission (CR1) who underwent myeloablative allo-HCT with either in vivo T cell-depleted (TCD) with antithymocyte globulin (ATG) within the European group for Blood and Marrow Transplantation (EBMT) centers or ex vivo TCD CD34 selected (CD34+) graft at the Memorial Sloan Kettering Cancer Center (MSKCC)
With the TCD techniques utilized by the MSKCC group that allow 3 to 4 logs of T cell depletion, Devine et al reported a cumulative incidence of grade III–IV aGVHD and extensive chronic graft-versus-host disease (GVHD) (cGVHD) of 4.5% and 6.8%, respectively, in a multicenter prospective phase 2 trial [15]
Summary
Graft-versus-host disease (GVHD) is one of the leading causes of non-relapse mortality and morbidity after allogeneic hematopoietic stem cell transplantation (allo-HCT). Since 2000, five phase III randomized trials have investigated the efficacy of rabbit ATG for GVHD prophylaxis in patients who received myeloablative (MAC) allo-HCT from unrelated or HLA-identical matched donors [7,8,9,10,11,12,13] In all these studies, the use of ATG was associated with a protective effect against cGVHD and in all but one study [12], overall survival (OS) and progression-free survival were not significantly affected [13]. To compare the efficacy of both approaches, we retrospectively evaluated the outcomes of patients with intermediate or high-risk AML in first complete remission (CR1) who underwent myeloablative allo-HCT with either in vivo TCD with ATG within the European group for Blood and Marrow Transplantation (EBMT) centers or ex vivo TCD CD34 selected (CD34+) graft at the Memorial Sloan Kettering Cancer Center (MSKCC)
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