High Incidence of Severe TA-TMA Increases Mortality in adult Allogeneic Transplant recipients: A prospective MIDAS Consortium study.

Abstract

No prospective study has evaluated the incidence of TA-TMA in adult allogeneic hematopoietic cell transplant (HCT) recipients. The MIDAS (MIcroangiopathy, endothelial Damage in Adults undergoing Stem cell transplantation) consortium conducted the first multi-center study to prospectively screen for TA-TMA. Longitudinal blood samples and detailed clinical data were collected weekly through day +100 and at months 5, 6, 9 and 12 in first allogeneic HCT recipients at three sites (Ohio State University, Moffitt and Roswell Park Comprehensive Cancer Centers). Adjudication of TA-TMA diagnosis was reviewed in real time by three blinded independent reviewers. Incidence of TA-TMA was scored using 6 published criteria: Harmonization, Jodele, Li, BMT-CTN, IWG and Cho, as well as the center-reported diagnosis and MIDAS adjudication categorized as no TMA, non-severe, or severe TA-TMA. Incidence of severe TA-TMA by day +100 was similar across the three centers at 21.8%, with a median time to onset of 14.5 days in 239 patients. Incidence of non-relapse mortality was 42% in severe compared to 8.4% in non-severe and 5.8% in no TMA groups (p<0.001). Rise in serum creatinine as early as day +7 and occurrence of hypertension by day+14 post-HCT were early indicators of severe TA-TMA. Our prospective study of systematic screening for TA-TMA identifies a higher incidence of a clinically impactful phenotype of TA-TMA than previously reported in adult HCT recipients. Our natural history study provides an essential foundation for urgently needed studies of prophylaxis and treatment of TA-TMA in adults and suggests clinical value in our inexpensive screening strategy.