TA-TMA as a clinical model for precision complement therapeutics in stem cell transplantation
- 1Division of Bone Marrow Transplantation and Immune Deficiency, Cancer and Blood Disease Institute, Cincinnati Children’s Hospital Medical Center
- 2Department of Pediatrics, University of Cincinnati College of Medicine
Abstract
Transplant-associated thrombotic microangiopathy (TA-TMA) has evolved from a poorly understood and frequently fatal complication of hematopoietic stem cell transplantation (HSCT) into the leading clinical model for precision complement therapeutics. Studies of TA-TMA have established endothelial injury and complement dysregulation as clinically actionable mechanisms and demonstrated that successful complement inhibition requires more than selecting an effective therapeutic agent. Longitudinal pharmacokinetic/pharmacodynamic (PK/PD)-guided dosing, durable terminal complement blockade, and integration of biomarkers reflecting complement activation, endothelial injury, inflammation, and organ dysfunction have transformed eculizumab into the first example of individualized complement-directed therapy in transplantation. Beyond improving outcomes in patients with TA-TMA, these advances have fundamentally changed our understanding of post-transplant endothelial injury, revealing shared biological pathways across multiple transplant-associated complications and supporting a transition from syndrome-based to mechanism-based clinical management. The expanding availability of eculizumab biosimilars and complement pathway-specific inhibitors, including lectin pathway inhibition, further broadens opportunities for personalized therapeutic strategies while emphasizing the need for harmonized diagnostic criteria, standardized response assessment, and biomarker-guided patient selection. Together, the lessons learned from TA-TMA provide a framework for future precision complement therapeutics in transplantation and illustrate how mechanistic understanding of disease biology can transform clinical practice.
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BibTeX
@article{jodele2026tatma,
title = {{TA-TMA as a clinical model for precision complement therapeutics in stem cell transplantation}},
author = {Sonata Jodele},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1959683},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1959683/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - TA-TMA as a clinical model for precision complement therapeutics in stem cell transplantation
AU - Sonata Jodele
PY - 2026
DA - 2026/10/12
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1959683
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1959683/full
AB - Transplant-associated thrombotic microangiopathy (TA-TMA) has evolved from a poorly understood and frequently fatal complication of hematopoietic stem cell transplantation (HSCT) into the leading clinical model for precision complement therapeutics. Studies of TA-TMA have established endothelial injury and complement dysregulation as clinically actionable mechanisms and demonstrated that successful complement inhibition requires more than selecting an effective therapeutic agent. Longitudinal pharmacokinetic/pharmacodynamic (PK/PD)-guided dosing, durable terminal complement blockade, and integration of biomarkers reflecting complement activation, endothelial injury, inflammation, and organ dysfunction have transformed eculizumab into the first example of individualized complement-directed therapy in transplantation. Beyond improving outcomes in patients with TA-TMA, these advances have fundamentally changed our understanding of post-transplant endothelial injury, revealing shared biological pathways across multiple transplant-associated complications and supporting a transition from syndrome-based to mechanism-based clinical management. The expanding availability of eculizumab biosimilars and complement pathway-specific inhibitors, including lectin pathway inhibition, further broadens opportunities for personalized therapeutic strategies while emphasizing the need for harmonized diagnostic criteria, standardized response assessment, and biomarker-guided patient selection. Together, the lessons learned from TA-TMA provide a framework for future precision complement therapeutics in transplantation and illustrate how mechanistic understanding of disease biology can transform clinical practice.
SN - 1664-3224
ER -