Transplant-Associated Thrombotic Microangiopathy (TA-TMA) is a Multifactorial Disease Unresponsive to Immunosuppressant Withdrawal

Thesis (Master's)--University of Washington, 2019Background: Transplant-associated thrombotic microangiopathy (TA-TMA) after allogeneic hematopoietic cell transplantation (HCT) has not been well-characterized in large population studies with clinically adjudicated cases. Methods: We performed a retrospective cohort study of adults who underwent allogeneic HCT between 2006 and 2015 to determine the incidence of and risk factors for TA-TMA, and to describe its natural history and response to immunosuppressant withdrawal management. Results: Among 2145 patients in this study, 192 developed TA-TMA with a cumulative incidence of 7.6% by 100 days post-transplant. Independent pre-transplant risk factors included the receipt of a second (or third) allogeneic HCT, HLA-mismatched donor, and myeloablative conditioning with or without total body irradiation (TBI); post-transplant risk factors included the antecedent development of acute graft-versus-host disease (GVHD), diffuse alveolar hemorrhage (DAH), bacteremia, invasive aspergillosis, BK viremia, and higher sirolimus trough level. Among TA-TMA patients, 27% achieved hematologic resolution and 57% remained alive as of 90 days following diagnosis. Antecedent risk factors stratified patients into different survival groups, and immunosuppressant withdrawal alone was not associated with improved patient outcomes. Conclusion: TA-TMA is a heterogenous disease that occurs after allogeneic transplantation. Management with immunosuppressant withdrawal does not appear to impact patient outcomes. Until further evidence becomes available, the management of TA-TMA should focus on the treatment of underlying diseases