What is the optimal dose of Anti-Thymocyte Globulin (ATG) for unrelated Stem Cell Transplantation (SCT)?

From the Guidelines

The recommended dose of anti-thymocyte globulin (ATG) for unrelated stem cell transplantation (SCT) is typically 6-10 mg/kg for Thymoglobuline (rabbit ATG) or 20-40 mg/kg for ATG-F (Grafalon), as indicated in the most recent guidelines 1. When considering the dose of ATG for unrelated SCT, several factors should be taken into account, including the type of ATG used, the conditioning regimen, and the patient's disease status and comorbidities.

• The dose of ATG may vary depending on the specific conditioning regimen used, with some regimens incorporating ATG at a dose of 10 mg/kg or ATG-F at a dose of 40 mg/kg 1.
• The choice of ATG dose should be individualized based on the patient's risk factors for GVHD and graft rejection, as well as their overall health status.
• Close monitoring for adverse effects, including infusion reactions and serum sickness, is essential during and after ATG administration.
• The use of ATG in unrelated SCT has been shown to reduce the risk of GVHD and improve outcomes, but the optimal dose and regimen remain a subject of ongoing research and debate 1.
• In general, the dose of ATG should be adjusted based on the patient's response to treatment and their overall health status, with the goal of minimizing the risk of GVHD and graft rejection while maximizing the chances of a successful transplant.

From the Research

ATG Dose for Unrelated SCT

• The optimal dose of Anti-Thymocyte Globulin (ATG) for unrelated donor stem cell transplantation (SCT) has not been fully determined 2.
• A study published in 2020 found that a dose of 2.5 mg/kg ATG in conditioning reduced the incidence of GVHD in unrelated donor transplants, but the actual dose of ATG given to patients was not associated with GVHD, relapse, or mortality 2.
• Another study published in 2022 used individualised dosing of ATG based on body weight, absolute lymphocyte counts, and stem-cell source, with cumulative doses ranging from 2-10 mg/kg, and found that this approach led to improved CD4+ immune reconstitution without increasing GVHD and graft failure incidence 3.
• A 2024 study found that lower-dose ATG-based regimens (2.5 mg/kg or 4.5 mg/kg) may potentially lead to improved outcomes in patients undergoing mismatched unrelated donor allogeneic HCT, with no difference in outcomes between the two doses 4.
• Other studies have also investigated the use of low-dose ATG in unrelated donor transplantation, with one study finding that a dose of 3 mg/kg reduced the incidence of chronic GVHD 5, and another study using a dose of 4.5 mg/kg in combination with tacrolimus and sirolimus for the prevention of acute GVHD 6.

Key Findings

• The use of ATG in unrelated donor SCT can reduce the incidence and severity of GVHD.
• The optimal dose of ATG has not been fully determined, but lower-dose regimens may be effective in reducing GVHD and improving outcomes.
• Individualised dosing of ATG based on patient characteristics may lead to improved CD4+ immune reconstitution and outcomes.

Dosing Regimens

• 2.5 mg/kg ATG in conditioning has been shown to reduce the incidence of GVHD in unrelated donor transplants 2.
• 3 mg/kg ATG has been shown to reduce the incidence of chronic GVHD 5.
• 4.5 mg/kg ATG has been used in combination with tacrolimus and sirolimus for the prevention of acute GVHD 6.
• Individualised dosing regimens based on body weight, absolute lymphocyte counts, and stem-cell source have been used, with cumulative doses ranging from 2-10 mg/kg 3.