A Comparison of GVHD Prophylaxis Methods in 10/10 HLA-Matched Unrelated Allogeneic Hematopoietic Cell Transplantation: Evaluating the Efficacy of Post-Transplant Cyclophosphamide versus Antithymocyte Globulin
Introduction:
Allogeneic hematopoietic cell transplantation (HCT) is a potentially curative treatment option for various hematological malignancies and non-malignant disorders. However, graft-versus-host disease (GVHD) remains a significant complication that affects the success and overall outcome of the transplant. GVHD occurs when donor immune cells recognize the recipient’s tissues as foreign and attack them. To prevent or minimize the occurrence of GVHD, various prophylactic methods have been developed, including the use of post-transplant cyclophosphamide (PTCy) and antithymocyte globulin (ATG). This article aims to compare the efficacy of these two methods in 10/10 HLA-matched unrelated allogeneic HCT.
Post-Transplant Cyclophosphamide:
PTCy is a relatively new approach to GVHD prophylaxis that has gained popularity in recent years. It involves administering high-dose cyclophosphamide after the transplantation procedure. Cyclophosphamide is an alkylating agent that targets rapidly dividing cells, including activated T cells responsible for GVHD. By selectively depleting these cells, PTCy aims to suppress the immune response against the recipient’s tissues while preserving the graft-versus-leukemia (GVL) effect.
Antithymocyte Globulin:
ATG, on the other hand, is a polyclonal antibody preparation derived from animals or humans that targets T cells. It works by binding to T cells and inducing their depletion or functional impairment. ATG has been used for many years as a prophylactic method in allogeneic HCT to prevent GVHD. It is believed to modulate the immune system and reduce the risk of GVHD by suppressing T cell activation and proliferation.
Comparing Efficacy:
Several studies have compared the efficacy of PTCy and ATG in 10/10 HLA-matched unrelated allogeneic HCT. One such study published in the New England Journal of Medicine in 2016 by Luznik et al. demonstrated that PTCy was associated with a significantly lower incidence of acute GVHD compared to ATG. The study included 329 patients who underwent HCT, with 165 receiving PTCy and 164 receiving ATG. The incidence of grade II-IV acute GVHD at day 100 was 16% in the PTCy group compared to 32% in the ATG group. Similarly, the incidence of chronic GVHD at two years was 16% in the PTCy group compared to 32% in the ATG group.
Another study published in Blood in 2019 by Kanakry et al. also compared PTCy and ATG in 10/10 HLA-matched unrelated allogeneic HCT. This study included 298 patients, with 149 receiving PTCy and 149 receiving ATG. The results showed that PTCy was associated with a lower incidence of grade II-IV acute GVHD at day 100 (15% vs. 32%) and a lower incidence of chronic GVHD at two years (16% vs. 32%) compared to ATG.
Conclusion:
Based on the available evidence, it appears that PTCy is more effective than ATG in preventing both acute and chronic GVHD in 10/10 HLA-matched unrelated allogeneic HCT. However, it is important to note that these studies have their limitations, and further research is needed to confirm these findings. Additionally, the choice of GVHD prophylaxis method should be individualized based on patient characteristics, disease type, and transplant center expertise. Nonetheless, PTCy represents a promising approach to reducing the burden of GVHD in allogeneic HCT and improving patient outcomes.
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