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 transplant-associated thrombotic microangiopathy (TA-TMA) in adult allogeneic hematopoietic cell transplant (HCT) recipients. The MIDAS (microangiopathy, endothelial damage in adults undergoing stem cell transplantation) Consortium conducted, to our knowledge, the first multicenter 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 from first allogeneic HCT recipients at 3 sites (The Ohio State University, Moffitt Cancer Center, and Roswell Park Comprehensive Cancer Center). Adjudication of TA-TMA diagnosis was reviewed in real time by 3 blinded independent reviewers. Incidence of TA-TMA was scored using 6 published criteria, as well as the center-reported diagnosis and MIDAS adjudication categorized as none, nonsevere, or severe TA-TMA. Incidence of severe TA-TMA by day +100 was similar across the 3 centers at 21.8%, with a median onset of 14.5 days in 239 patients. Incidence of nonrelapse mortality was 42% in severe compared with 8.4% in nonsevere and 5.8% in no-TMA groups (P < .001). Rise in serum creatinine as early as day +7 and occurrence of hypertension by day +14 after 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 TA-TMA prophylaxis and treatment in adults and suggests clinical value in our inexpensive screening strategy.