Evaluation of ATG vs ATLG on Immune Recovery and Infections Post-AHSCT in MS

Overview

This study compared the effects of anti-thymocyte globulin (ATG) and anti-T-lymphocyte globulin (ATLG) on immune reconstitution and early infections following autologous hematopoietic stem cell transplantation (AHSCT) in multiple sclerosis (MS) patients. Patients receiving pre-transplant ATLG showed significantly faster immune recovery at day 30 post-transplant compared to those receiving post-transplant ATG. Infection rates and viral reactivations were also assessed to evaluate safety profiles.

Background

Multiple sclerosis is a chronic autoimmune disease characterized by neuroinflammation and neurodegeneration. Autologous hematopoietic stem cell transplantation (AHSCT) is an established treatment for aggressive or treatment-resistant MS, aiming to reset the immune system. Conditioning regimens typically include high-dose chemotherapy combined with lymphodepleting serotherapy such as ATG or ATLG. However, there is variability in serotherapy dosing and timing, and comparative data on their effects on immune recovery and infection risk are limited. This study evaluates these parameters in MS patients undergoing AHSCT with cyclophosphamide-based conditioning.

Data Highlights

Key Findings

• Patients receiving pre-transplant ATLG exhibited significantly faster immune reconstitution at day 30 post-AHSCT, with higher counts of total T cells (CD3+), helper T cells (CD4+), memory T helper cells (CD4+/CD45RO+), and cytotoxic T cells (CD8+).
• Both ATG and ATLG groups had comparable baseline characteristics and similar hematopoietic recovery times (median 10 days for neutrophils and platelets).
• ATG was predominantly administered post-transplant at a cumulative dose of 7.5 mg/kg, whereas ATLG was mostly given pre-transplant at a total dose of 30 mg/kg.
• EBV and CMV viral loads were monitored, with definitions for significant reactivation established, though specific comparative infection rates were not detailed in the excerpt.
• Variation exists in serotherapy dosing and scheduling across centers, highlighting the need for harmonized conditioning regimens.

Clinical Implications

The faster immune recovery observed with pre-transplant ATLG suggests it may offer advantages in early immune reconstitution post-AHSCT in MS patients. Clinicians should consider the timing and type of anti-T cell serotherapy as these factors influence lymphocyte recovery and potentially infection risk. Monitoring for viral reactivations remains essential regardless of serotherapy choice.

Conclusion

Pre-transplant administration of ATLG leads to more rapid immune reconstitution compared to post-transplant ATG in MS patients undergoing AHSCT, supporting further evaluation of serotherapy timing to optimize transplant outcomes. Harmonization of conditioning protocols may improve consistency in patient care.

References

1. EBMT Guidelines 2020 -- Conditioning Regimens for AHSCT in MS
2. Study Authors 2025 -- Evaluation of Anti-Human T Cell Globulins on Immune Recovery and Initial Infections Following Autologous Transplantation in Multiple Sclerosis Patients