ATG and other serotherapy in conditioning regimens for autologous HSCT in autoimmune diseases: a survey on behalf of the EBMT Autoimmune Diseases Working Party (ADWP) - Report - MDSpire
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ATG and other serotherapy in conditioning regimens for autologous HSCT in autoimmune diseases: a survey on behalf of the EBMT Autoimmune Diseases Working Party (ADWP)
Evaluation of ATG and Alternative Serotherapy in Conditioning for Autologous HSCT in Autoimmune Disorders
Overview
A survey of 46 EBMT centers revealed that anti-thymocyte globulin (ATG) is universally used in conditioning regimens for autologous HSCT in autoimmune diseases, predominantly Cyclophosphamide-ATG (Cy-ATG). Variability exists in ATG dosing, administration schedules, and adjunctive use of rituximab, with notable disease-specific adverse effects reported during serotherapy.
Background
Autologous hematopoietic stem cell transplantation (HSCT) is an established treatment for severe autoimmune diseases such as multiple sclerosis and systemic sclerosis. Conditioning regimens commonly include serotherapy with polyclonal anti-thymocyte globulin (ATG) to deplete host and graft T-cells, facilitating immune resetting. Alternative monoclonal antibodies like rituximab and alemtuzumab are also used, though alemtuzumab was not reported in this survey. Understanding real-world practices in serotherapy administration can help optimize HSCT outcomes and minimize adverse effects.
Data Highlights
Parameter
Value/Description
Number of centers surveyed
46 (66% response rate)
Countries represented
18
Centers performing HSCT for neurological AD
11 (23.9%)
Centers performing HSCT for rheumatological AD
7 (15.2%)
Centers performing HSCT for multiple indications
27 (58.7%)
Use of ATG
100% of centers
Use of rituximab with ATG
12 centers (26.1%)
Use of alemtuzumab
0 centers
Most common conditioning regimen
Cy-ATG
Most common ATG type
Thymoglobulin (89.1% centers)
ATG total dose (Thymoglobulin)
32.6% use 7.5 mg/kg, 53.6% use <7.5 mg/kg, 4.3% use >7.5 mg/kg
Centers reporting pseudo-relapse in neurological AD
MS: 12 centers, NMO: 4 centers, CIDP: 5 centers
Centers reporting cardiac toxicity in rheumatological AD
14 centers
Centers reporting renal crises in rheumatological AD
8 centers
Key Findings
All surveyed EBMT centers use ATG in conditioning regimens for autologous HSCT in autoimmune diseases, with Cy-ATG being the most common protocol.
Thymoglobulin is the predominant ATG preparation used, with dosing varying mostly between less than and equal to 7.5 mg/kg total dose.
Rituximab is used adjunctively in about one-quarter of centers, but alemtuzumab is not currently used.
ATG administration schedules vary, typically fractionated over 3 to 5 days with infusion durations ranging from 6 to 12 hours.
Premedication with antihistamines, steroids, and paracetamol is universally or near-universally employed to mitigate infusion-related adverse effects.
Disease-specific complications during serotherapy include pseudo-relapses in neurological autoimmune diseases and cardiac, renal, and pulmonary toxicities in rheumatological diseases, especially systemic sclerosis.
Clinical Implications
Standardization of ATG dosing and administration protocols could improve consistency of HSCT outcomes and reduce adverse events. Clinicians should be vigilant for disease-specific complications such as pseudo-relapses in neurological autoimmune diseases and organ toxicities in systemic sclerosis during conditioning. Premedication remains essential to prevent infusion-related reactions. The adjunctive use of rituximab warrants further study to clarify its role and optimize timing relative to chemotherapy and HSCT.
Conclusion
This survey highlights widespread use of ATG-based serotherapy in autologous HSCT conditioning for autoimmune diseases with notable variability in dosing and administration practices. Awareness of disease-specific adverse effects and harmonization of protocols may enhance safety and efficacy of HSCT in this setting.
References
EBMT Autoimmune Diseases Working Party (ADWP) -- Evaluation of ATG and Alternative Serotherapy in Conditioning Protocols for Autologous HSCT in Autoimmune Disorders
