TA-TMA Is Frequent, but Not All TA-TMA Is Actionable in Adult Allogeneic HCT Patients: A Report from the MIDAS (Microangiopathy, Endothelial Damage in Adults undergoing Stem cell transplantation) Consortium.

Transplant-associated thrombotic microangiopathy (TA-TMA) can be associated with significant morbidity and mortality but is under-studied in adults. An expert consensus panel recently published Modified Jodele Criteria (MJC) to define TA-TMA with the intent for adoption across transplant registries and centers (PMID: 36442770).We performed the first study in adults applying MJC criteria for TA-TMA in a prospective cohort with weekly biospecimen and data collection through day+100 after allogeneic HCT. The MIDAS Consortium consists of 3 adult HCT centers, with a plan to enroll 1000 first allo HCT patients. Herein we report on the first 101 patients who have reached 1-year post-HCT (Table). TA-TMA was adjudicated using the MJC definition by a 3-member panel who were blinded to each other and to the HCT center's reporting of TA-TMA.We defined severe TA-TMA as meeting the MJC definition while also having end-organ damage (new hypertension, neurologic manifestations, renal dysfunction, proteinuria) OR high transfusion requirements. Median follow up in the first 101 patients was 344.5 days post-HCT.At day+100 post-HCT, the cumulative incidence of TA-TMA by MJC was 46.8% (95% CI 36.8-56.2%) and severe TA-TMA was 17% (95% CI 10.4-24.9%), neither of which significantly differed by center. TA-TMA defined by MJC was significantly associated with 1-year overall survival (OS) and non-relapse mortality (NRM, Figure 1A, 1B). OS and NRM were significantly affected by severe TA-TMA but not by not-severe TA-TMA. (Figure 1C, 1D).The proportion of patients with severe TA-TMA increased with increasing severity of acute GVHD (Figure 2). TA-TMA preceded GVHD in patients with grade I or II acute GVHD, while most patients with grade III-IV acute GVHD were diagnosed concurrently with severe TA-TMA.Concordance of TA-TMA diagnosis between the MIDAS panel and HCT center was low. Of 17 patients adjudicated as severe TA-TMA by MIDAS, 10 were reported as having TA-TMA by the center, with 8 receiving TA-TMA-directed therapy (6 eculizumab, 2 other) and only 2 of 8 survived (both received eculizumab). Of 23 patients adjudicated as MJC-defined TA-TMA that was not severe, 5 were reported as TA-TMA by the center, with 5 receiving TA-TMA-directed therapy (2 eculizumab, 3 other). All 5 of these patients remain alive at last follow-up. Both MJC defined and severe TA-TMA were under-reported by the centers.TA-TMA as defined by MJC is frequent in adults after allogeneic HCT, but not all TA-TMA is actionable. Actionable cases of severe TA-TMA can be identified by end-organ damage and high transfusion requirements. Weekly biospecimens have been collected up to day+100 and will be analyzed for biomarkers associated with development and prognosis of TA-TMA.