Transplant Associated Thrombotic Microangiopathy (TA-TMA): Lessons Learned from a Large Pediatric Center

Background Transplant associated thrombotic microangiopathy (TA-TMA) is a well-recognized complication of hematopoietic cell transplantation (HCT) but is very challenging to diagnose. Outcomes are historically poor, though it is unclear if this is secondary to TA-TMA or to concurrent morbid conditions. We aimed to describe the prevalence and outcomes of TA-TMA at a single large pediatric center. Methods In this retrospective study, medical records of all children who received an HCT at Boston Children's Hospital from 1/2015-08/2017 were reviewed for evidence of TA-TMA in the first 100 days after HCT. Patients were diagnosed using "probable diagnostic TA-TMA criteria" (Cho et al, 2010). Patients who were both clinically diagnosed and retrospectively met criteria for TA-TMA were grouped together for analysis. Results 275 HCTs were performed in 232 patients. 37 patients (16%) met criteria for TA-TMA; 6 were clinically diagnosed and 31 retrospectively met criteria. TA-TMA was diagnosed a median of 26 days (range 11-97 days) after cell infusion. Patients with TA-TMA had significantly higher rates of aGVHD, ICU admissions, engraftment failure, bacterial and or viral infections in the first 100 days and were more likely to have an unrelated donor HCT, an HLA-loci mismatch of OS was significantly lower in patients with TA-TMA, with a one-year OS of 63.1% (95% CI=46.8-79.3%) vs 92.1% (87.9-96.2%), (p Of the 6 patients diagnosed with TA-TMA by providers, 4/6 were treated with eculizumab; 2 died of multiorgan failure and 2 remained dependent on eculizumab for ³2 years to maintain control of disease. The other 2 patients changed aGVHD prophylaxis resulting in TA-TMA resolution. Of the 31 patients who retrospectively met criteria none received TA-TMA directed therapy. One-year TRM was not significantly different between those diagnosed clinically versus retrospectively. Conclusion Most patients who met criteria for TA-TMA were retrospectively identified while being treated for another transplant complication (31/37), highlighting the challenge of a clinical diagnosis in the setting of non-specific criteria. Patients with TA-TMA had worse OS and increased TRM, even when adjusting for the development of aGVHD and engraftment failure (HR 9.1). It is important to develop multi-institutional, prospective studies to identify risk factors for TA-TMA and further study therapies and outcomes.