Impact of graft-versus-host disease after reduced-intensity conditioning allogeneic stem cell transplantation for acute myeloid leukemia: a report from the Acute Leukemia Working Party of the European group for blood and marrow transplantation

Abstract

This report investigated the impact of graft-versus-host disease (GVHD) on transplantation outcomes in 1859 acute myeloid leukemia patients given allogeneic peripheral blood stem cells after reduced-intensity conditioning (RIC allo-SCT). Grade I acute GVHD was associated with a lower risk of relapse (hazards ratio (HR) ¼ 0.7, P ¼ 0.02) translating into a trend for better overall survival (OS; HR ¼ 1.3; P ¼ 0.07). Grade II acute GVHD had no net impact on OS, while grade III-IV acute GVHD was associated with a worse OS (HR ¼ 0.4, Po0.0.001) owing to high risk of nonrelapse mortality (NRM; HR ¼ 5.2, Po0.0001). In time-dependent multivariate Cox analyses, limited chronic GVHD tended to be associated with a lower risk of relapse (HR ¼ 0.72; P ¼ 0.07) translating into a better OS (HR ¼ 1.8; Po0.001), while extensive chronic GVHD was associated with a lower risk of relapse (HR ¼ 0.65; P ¼ 0.02) but also with higher NRM (HR ¼ 3.5; Po0.001) and thus had no net impact on OS. In-vivo T-cell depletion with antithymocyte globulin (ATG) or alemtuzumab was successful at preventing extensive chronic GVHD (Po0.001), but without improving OS for ATG and even with worsening OS for alemtuzumab (HR ¼ 0.65; P ¼ 0.001). These results highlight the role of the immune-mediated graft-versus-leukemia effect in the RIC allo-SCT setting, but also the need for improving the prevention and treatment of severe GVHD.

Better outcomes of modified myeloablative conditioning without antithymocyte globulin versus myeloablative conditioning in cord blood transplantation for hematological malignancies: A retrospective (development) and a prospective (validation) study

“…reported that among patients with pretransplantation minimal residual disease, OS after CBT was as favorable as HCT with HLA‐matched unrelated donor and much higher than HCT with HLA‐mismatched unrelated donor, and the probability of relapse was lower in the cord‐blood group than in either of the other groups, which indicated that cord blood may have a stronger GVL effect than other graft sources. In this study, we found that both relapse rate and cGVHD rate were lower in the MMAC group, which seemed to be inconsistent with the previous reports as some authors believed that GVL effect was closely related to cGVHD 38, 39, 40. Nevertheless, most of these studies were designed for HCT with matched sibling donors, haploidentical‐related donors and unrelated donors, the GVL effects of CBT may work in a different way.…”

Impact of the source of hematopoietic stem cell in unrelated transplants: Comparison between 10/10, 9/10‐HLAmatched donors and cord blood

“…It highlights the role of ATG, which protects against acute and chronic GVHD [30]. Unfortunately, this positive effect is counterbalanced by an increased incidence of relapse, as observed in previous reports [31,32], eventually resulting in similar survival rates. In this report, high-risk patients according to the last CIBMTR disease risk classification were found to harbor higher aGVHD, higher relapse, and impaired survival rates compared with other groups.…”

Long-term results of adjuvant donor lymphocyte transfusion in AML after allogeneic stem cell transplantation

“…25 However, this seems to be counterbalanced to some extent by more standard myeloablative conditioning and a less frequent use of in vivo T-cell depletion in this very group, both being assumed to be associated with a higher antileukemic activity. 26,27 In conclusion, this study demonstrates that adjuvant, unmanipulated DLT from related and unrelated donors are safe and highly effective in preventing post-transplantation relapse in highrisk AML. Eligible patients treated with aDLT have an excellent chance for long-term survival in spite of high-risk disease.…”