What is the optimal dose of Anti-Thymocyte Globulin (ATG) for Graft-Versus-Host Disease (GVHD) prophylaxis?

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Last updated: April 1, 2025View editorial policy

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From the Guidelines

For GVHD prophylaxis, ATG (anti-thymocyte globulin) is typically administered at a dose of 2.5-10 mg/kg total, divided over 2-4 days pre-transplant, with the most recent and highest quality study suggesting a dose range of 6–10 mg/kg for Thymoglobuline and 20–40 mg/kg for ATG-F 1.

Key Considerations

  • The dose of ATG can vary depending on the specific product used, with Thymoglobuline (rabbit ATG) typically given at a dose of 4.5-7.5 mg/kg total, and ATGAM (horse ATG) given at a dose of 30-40 mg/kg total 1.
  • Administration of ATG usually begins 3-4 days before stem cell infusion, and it is typically given as a slow IV infusion over 4-6 hours through a central line, with premedication including antipyretics, antihistamines, and corticosteroids to minimize infusion reactions 1.
  • ATG works by depleting T-cells, which are the primary mediators of GVHD, thereby reducing the risk of this serious transplant complication.
  • It's particularly beneficial in unrelated donor transplants or mismatched transplants where GVHD risk is higher.
  • ATG is typically used as part of a multi-drug regimen that often includes a calcineurin inhibitor (cyclosporine or tacrolimus) and methotrexate or mycophenolate mofetil.

Important Details

  • The optimal conditioning regimen for a patient should be selected based on the type and status of the disease, comorbidities, underlying conditions, and donor source 1.
  • The use of ATG in GVHD prophylaxis has been associated with a reduced risk of GVHD, but it also increases the risk of infections and other complications 1.
  • The choice of ATG product and dose should be individualized based on the patient's specific needs and risk factors.
  • Close monitoring of vital signs and laboratory parameters is essential during ATG administration to minimize the risk of adverse reactions.

From the FDA Drug Label

ATG-R 2 mg/kg IV administered once per day for 3 consecutive days pre-implantation (3 total doses) The dose of ATG-R (antithymocyte globulin [rabbit]) for GVHD prophylaxis is 2 mg/kg IV administered once per day for 3 consecutive days pre-implantation, for a total of 3 doses 2.

From the Research

ATG Dose for GVHD Prophylaxis

  • The optimal dose of Antithymocyte Globulin (ATG) for Graft-versus-Host Disease (GVHD) prophylaxis has not been established, with various studies suggesting different dosing regimens 3, 4, 5, 6, 7.
  • A study published in 2017 found that a low-dose ATG regimen (2.5 mg/kg) was effective in reducing GVHD rates in matched unrelated donor allogeneic hematopoietic stem cell transplantation 3.
  • Another study published in 2024 analyzed outcomes of HLA 9/10 mismatched unrelated donor allogeneic HCTs using lower-dose ATG-based regimens and found that the dose of ATG (2.5 mg/kg vs. 4.5 mg/kg) was not associated with outcomes in either univariate or multivariate analyses 4.
  • A 2023 study found that the use of ATG at 5 mg/kg was highly effective in limiting the occurrence of both acute and chronic GVHD, ensuring a low non-relapse mortality and relapse incidence 5.
  • A comparative study published in 2025 found that low-dose ATG-Fresenius (15mg/kg) and ATG-Thymoglobulin (10mg/kg) had similar safety and efficacy outcomes for GVHD prevention 6.
  • A 2015 study found that a lower dose of ATG-Fresenius (35 mg/kg) resulted in improved survival after allogeneic stem cell transplantation, with reduced transplant-related mortality and no increase in disease relapse 7.

Key Findings

  • Low-dose ATG regimens (2.5-5 mg/kg) may be effective in reducing GVHD rates without significant differences in relapse incidence or survival 3, 4, 5.
  • The optimal dose of ATG for GVHD prophylaxis may depend on various factors, including the type of ATG used, the conditioning regimen, and the patient's underlying disease and risk factors 6, 7.
  • Further studies are needed to determine the ideal GVHD prophylaxis regimen and to compare the safety and efficacy of different ATG dosing regimens 3, 4, 5, 6, 7.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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