Transplantation-associated thrombotic microangiopathy is associated with transplantation from unrelated donors, acute graft-versus-host disease and venoocclusive disease of the liver

Abstract

Transplantation-associated thrombotic microangiopathy (TA-TMA) has been associated with significantly reduced survival following allogeneic bone marrow transplantation. In this study we describe the course and response to plasma exchange therapy of TA-TMA as well as risk factors for its' development. Twenty-five patients who underwent plasma exchange therapy were matched to fifty control patients selected for transplant indication and stage of disease at the time of transplant. Transplant indications were acute myeloid leukemia, acute lymphoblastic leukemia, chronic myeloid leukemia, aplastic anemia, myelodysplastic syndrome and multiple myeloma. Groups were well balanced with respect to disease status, age at time of transplant and use of radiation-based conditioning. TA-TMA was diagnosed a median of 27 days after transplantation and neurological abnormalities were present in ten cases. Patients received a median of 10 (range 2-43) plasma exchange treatments. Hematological responses were recorded in eight cases. Risk factors for the development of TA-TMA included transplantation from unrelated donors (p = 0.002), hepatic venoocclusive disease (VOD) (p = 0.034), grade 2-4 acute graft-versus-host disease (GVHD) (p = 0.042) and bacteremia with diphtheroid organisms (p = 0.009). Only hepatic VOD (p = 0.0026) and grade 2-4 acute GVHD (p = 0.0436) remained significant risk factors for later development of TA-TMA in a multivariate logistic regression model. The median survival of patients with TA-TMA was 66 (range 32-733) days while that of unaffected patients was 742 (range 15-2392) days after transplantation. Only one patient with TA-TMA remains alive 733 days after transplantation.