TA-TMA and GVHD Are Distinct Consequences of Endothelial Injury: A MIDAS Consortium Study

Published in Blood Advances, researchers from the MIDAS consortium, including Roswell Park Comprehensive Cancer Center, The Ohio State University, Cincinnati Children’s Medical Center, and Moffitt Comprehensive Cancer Center, have demonstrated that transplant-associated thrombotic microangiopathy (TA-TMA) and graft-versus-host disease (GVHD) are related, but distinct consequences of endothelial injury after allogeneic hematopoietic cell transplantation (HCT). This study demonstrates that post-transplant cyclophosphamide (PTCy) reduces acute GVHD but does not reduce TA-TMA, highlighting the need for prospective TA-TMA screening even in patients receiving modern GVHD prophylaxis.

Acute GVHD is a known risk factor for TA-TMA, but it is unclear whether these complications represent the same endothelial injury process or separate clinical entities. Prior TA-TMA biomarker work has largely focused on pediatric HCT, while adult data remain limited. Therefore, the authors sought to delineate the relationship between GVHD and TA-TMA by analyzing the prospective, multicentre MIDAS cohort of 368 adults undergoing first allogeneic HCT. Weekly clinical and biospecimen collection to day +100 and follow-up to 1 year were assessed and TA-TMA was adjudicated by a blinded 3-member panel. Acute GVHD was graded by Glucksberg criteria, and biomarkers were measured before HCT and after transplant.

By day +100, cumulative incidence was 44.9% for any TA-TMA and 18.5% for severe TA-TMA; 165 patients developed any TA-TMA and 68 developed severe TA-TMA. Acute GVHD grade II–IV occurred in 146 patients, grade III–IV in 54, and steroid-refractory acute GVHD in 36. TA-TMA preceded acute GVHD in more than half of patients who developed both; among those with both severe TA-TMA and acute GVHD, 28/51 (55%) had TA-TMA first. Severe TA-TMA occurred in 11% of patients with no acute GVHD, 8% with grade I, 19% with grade II, and 54% with grade III/IV acute GVHD. PTCy-based prophylaxis reduced acute GVHD but had similar severe TA-TMA incidence to methotrexate-based prophylaxis (20% vs 17%). Pre-HCT creatinine, cystatin-C, and detectable PlGF predicted severe TA-TMA, while day +28 creatinine and ST2 remained significant in multivariable analyses. In sex-stratified models, a higher baseline creatinine increased TA-TMA risk by 5.27-fold in males and 40.38-fold in females. Overall, TA-TMA and GVHD have overlapping endothelial biology but distinct biomarker profiles, supporting adult-specific TA-TMA surveillance and risk stratification.

Reference:

Hahn T, Zhao Q, Miller EG, et al. TA-TMA and GVHD are distinct consequences of endothelial injury: A MIDAS consortium study. Blood Adv. Published online June 3, 2026. http:doi.org/10.1182/bloodadvances.2026019747