Posttransplant cyclophosphamide vs antithymocyte globulin in HLA-mismatched unrelated donor transplantation

Abstract

The use of anti-thymocyte globulin (ATG) has represented the standard of care in graft-versus-host disease (GVHD) prophylaxis in patients undergoing a mismatched unrelated donor (MMUD) transplant. The safety and feasibility of posttransplant cyclophosphamide (PTCY) in this setting have been reported recently, but no study has compared the outcomes of PTCY vs ATG in 9/10 MMUD transplants. Using the registry data of the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation, we performed a matched-pair analysis comparing those 2 strategies in a 9/10 MMUD setting. Ninety-three patients receiving PTCY were matched with 179 patients receiving ATG. A significantly lower incidence of severe acute GVHD was observed with PTCY compared with ATG. Recipients of the former also showed higher leukemia-free survival and GVHD/relapse-free survival (GRFS). When performing a subgroup analysis including patients receiving peripheral blood stem cells, being in complete remission, or receiving the same associated immunosuppressive agents, superiority of PTCY over ATG was confirmed. Similar to the haploidentical setting, use of PTCY is an effective anti-GVHD prophylaxis in the 9/10 MMUD transplant. Use of PTCY may also provide better outcomes in long-term disease control. These results need confirmation in large prospective randomized trials.

Post-transplant cyclophosphamide versus antithymocyte globulin in patients with acute myeloid leukemia in first complete remission undergoing allogeneic stem cell transplantation from 10/10 HLA-matched unrelated donors

“…Since then, PTCY has been applied in other settings, including HLAidentical sibling or UD and mismatched unrelated donor (MMUD) [21][22][23][24]. In the 9/10 MMUD setting, PTCY use was described as effective anti-GVHD prophylaxis compared to ATG and likely to provide better outcomes in long-term disease control [25]. This increase in evidence of the positive impact of PTCY, prompted us to evaluate its practical clinical use in allo-HSCT with MUD.…”

Post‐transplantation cyclophosphamide versus antithymocyte globulin in patients with acute myeloid leukemia undergoing allogeneic stem cell transplantation from HLA‐identical sibling donors: A retrospective analysis from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation

“…The recent introduction of PTCY in the haploidentical setting has shown promising results for the prevention of both acute and chronic GVHD, and it has been subsequently extended to other donor types, including HLA‐identical sibling and matched or mismatched unrelated donors 8‐10 …”

“…In recent years, the John Hopkins group pioneered the use of post‐transplantation cyclophosphamide (PTCY) in the HLA‐mismatched related donors setting, showing that this strategy is feasible and efficacious with low rates of both acute and chronic GVHD 7 . Subsequently, the use of PTCY has also been proposed in other donor settings, such as HLA‐identical sibling and unrelated donor transplantation, confirming its feasibility 8‐10 …”

NK cell alloreactivity in acute myeloid leukemia in the post‐transplant cyclophosphamide era

“…27 In comparison to the widely used GvHD prophylaxis with ATG in this donor transplantation, PTCy shows comparable results in GvHD and relapse rates 28,29 and sometimes even superiority. 30 Other HaploSCT platforms such as T cell replete haploSCT that incorporate an intense immunosuppressive ATG-based regimen (Beijing protocol), 31 have also been developed and show comparable results to the use of PTCy. 11,32 Owing to these results and the low cost of PTCy, haploSCT with PTCy has in many centers become the standard of care option for patients who lack an HLA-matched donor or are in need for an urgent transplant.…”