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Comparing GVHD Prophylaxis Methods in 10/10 HLA-Matched Unrelated Allogeneic Hematopoietic Cell Transplantation: Post-Transplant Cyclophosphamide vs. Antithymocyte Globulin

Comparing GVHD Prophylaxis Methods in 10/10 HLA-Matched Unrelated Allogeneic Hematopoietic Cell Transplantation: Post-Transplant Cyclophosphamide vs. Antithymocyte Globulin

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 the donor’s immune cells recognize the recipient’s tissues as foreign and attack them, leading to various clinical manifestations.

To prevent GVHD, different prophylaxis methods have been developed and tested over the years. Two commonly used approaches in 10/10 HLA-matched unrelated allogeneic HCT are post-transplant cyclophosphamide (PTCy) and antithymocyte globulin (ATG). Both methods aim to suppress the donor’s immune response against the recipient’s tissues, but they differ in their mechanisms of action and potential side effects.

PTCy is a relatively new approach that has gained popularity in recent years. It involves administering high-dose cyclophosphamide after the transplantation procedure. Cyclophosphamide targets rapidly dividing cells, including activated T cells responsible for GVHD. By selectively depleting these cells, PTCy helps prevent the development of GVHD while preserving the graft-versus-leukemia (GVL) effect, which is crucial for eradicating residual cancer cells.

One of the advantages of PTCy is its simplicity. It can be easily incorporated into the standard conditioning regimen without requiring additional medications or prolonged hospital stays. Additionally, PTCy has shown promising results in reducing both acute and chronic GVHD rates, making it an attractive option for patients undergoing 10/10 HLA-matched unrelated allogeneic HCT.

On the other hand, ATG has been used for many years as a GVHD prophylaxis method. It consists of polyclonal antibodies derived from animals, usually rabbits or horses, that target and deplete T cells. By suppressing the donor’s immune response, ATG reduces the risk of GVHD. However, it also affects the GVL effect to some extent, potentially compromising the transplant’s anti-cancer efficacy.

ATG is typically administered before the transplantation procedure as part of the conditioning regimen. It requires careful monitoring due to the risk of infusion reactions and other side effects, such as infections and prolonged immune suppression. Despite these drawbacks, ATG has demonstrated efficacy in reducing acute and chronic GVHD rates, especially in patients at high risk for developing GVHD.

Comparing PTCy and ATG in 10/10 HLA-matched unrelated allogeneic HCT, several studies have been conducted to evaluate their effectiveness and safety profiles. While both methods have shown promising results in reducing GVHD rates, PTCy appears to have an advantage in terms of preserving the GVL effect. This is particularly important for patients with hematological malignancies who rely on the transplant’s anti-cancer properties.

Furthermore, PTCy has been associated with lower rates of infectious complications compared to ATG. This is likely due to its selective targeting of activated T cells, which reduces overall immune suppression. In contrast, ATG’s broad immunosuppressive effects can increase the risk of infections and delay immune reconstitution.

However, it is important to note that the choice between PTCy and ATG should be individualized based on various factors, including patient characteristics, disease type, and transplant center expertise. Both methods have their advantages and disadvantages, and the decision should be made in consultation with a multidisciplinary transplant team.

In conclusion, comparing GVHD prophylaxis methods in 10/10 HLA-matched unrelated allogeneic HCT, PTCy and ATG have shown efficacy in reducing GVHD rates. PTCy offers the advantage of preserving the GVL effect and potentially lower rates of infectious complications. However, the choice between the two methods should be based on individual patient factors and expert recommendations. Further research is needed to optimize GVHD prophylaxis strategies and improve transplant outcomes.