Clinical Outcomes and Treatment Strategies of Adult Transplant‐Associated Thrombotic Microangiopathy: External Validation of Harmonizing Definitions and High‐Risk Criteria

Transplant-associated thrombotic microangiopathy (TA-TMA) is an endothelial dysfunction syndrome observed after allogeneic hematopoietic cell transplant (alloHCT). Our aim was to externally validate the impact of high-risk features on the clinical outcomes of adult patients meeting the updated TA-TMA harmonizing criteria. Between 2005 and 2022, 99 patients were diagnosed with TA-TMA at Mayo Clinic Rochester (incidence 6.2%) after a median of 137 days post alloHCT (IQR: 34-283 days). The development of TA-TMA was associated with an inferior overall survival posttransplant (HR: 3.8, 95% CI: 2.97-4.72). High-risk features, including concomitant infection, acute graft-versus-host disease (GVHD), and organ dysfunction, were associated with poor survival, while LDH elevation was not associated with inferior outcomes. The most common treatment strategy for TA-TMA was discontinuation of calcineurin or mTOR inhibitors in 80 (81%) patients. Thirty (37.5%) patients experienced worsening of GVHD with this strategy, of which 26 (86.7%) patients had died at last follow-up. The most common cause of death among these patients was worsening GVHD (69%; n = 18), followed by infection (11%; n = 3), disease relapse (8%; n = 2), other/unknown causes (8%; n = 2), or TA-TMA (4%; n = 1). Objective response rate (ORR) to initial treatment for the cohort was 56.6%. Eculizumab was used in 11 patients with an observed ORR of 70%, including 5 complete responses. In conclusion, TA-TMA remains a significant contributor to non-relapse mortality and is associated with worse survival following alloHCT. Not all high-risk features, particularly LDH elevation, have consistently demonstrated a negative impact in adult cohorts. Patients with TA-TMA may benefit from immune suppression dose adjustment, rather than a discontinuation, and the addition of complement-directed therapy, particularly among high-risk patients.