Abstract
High-risk transplant-associated thrombotic microangiopathy (hrTA-TMA), marked by organ dysfunction with concurrent graft-versus-host disease (GVHD) or infection, leads to poor outcomes after allogeneic hematopoietic cell transplantation (alloHCT). Terminal complement blockade is effective in pediatric patients with hrTA-TMA, but its efficacy and safety in adult patients are unclear. To compare clinical and safety outcomes of adults with hrTA-TMA treated with terminal complement blockade versus conventional therapy. We retrospectively included adults who underwent alloHCT between 2012 and 2023 and developed hrTA-TMA, defined per Harmonization criteria. Time-to-event analyses began at TA-TMA diagnosis, with outcomes including death, relapse, and non-relapse mortality (NRM). The impact of eculizumab on these outcomes was assessed using time-dependent Cox regression models. Models were adjusted for baseline TA-TMA biomarkers (lactate dehydrogenase, platelet count, and creatinine) to account for disease severity at diagnosis. A total of 47 hrTA-TMA patients were included: 16 received eculizumab, and 31 received conventional therapy. With a median follow-up of 7.3 yr, the 1-yr overall survival (OS) for entire cohort was 61% (95% CI, 47% to 75%), and 45% at 2 yr (95% CI, 31% to 60%). NRM was 32% at 1 yr (95% CI, 19% to 46%) and 44% at 2 yr (95% CI, 29% to 58%). Clinical response occurred in 56% with eculizumab and 71% with conventional therapy. The eculizumab cohort had worse OS (P < .001), with a higher hazard ratio (HR) for death at 6 mo (HR 5.8), 1 yr (HR 4.4), and 2 yr (HR 2.5). This was driven by increased NRM (P < .001) at 6 mo and 1 yr (HR 5.3) and 2 yr (HR 3.7), with no significant difference in relapse. Survival outcomes remained consistent after adjusting for hrTA-TMA biomarkers. Deaths were mainly due to infections in the eculizumab group versus GVHD in conventional therapy. In adults with hrTA-TMA after alloHCT, terminal complement blockade did not improve outcomes and was associated with higher NRM. Prospective studies are needed to better define its therapeutic role and optimal application in this setting.