Thrombotic microangiopathy in blood and marrow transplant patients receiving tacrolimus or cyclosporine A.

摘要

BACKGROUND: Cyclosporine A (CSA) and tacrolimus (FK-506) are both associated with thrombotic microangiopathy (TMA) in allogeneic BMT recipients, although it is not known which drug is more likely to cause the syndrome. The optimal treatment of BMT-associated TMA is also not known. STUDY DESIGN AND METHODS: To estimate the risks, predisposing factors, and outcomes of TMA, data were analyzed from two cohorts of BMT patients who had received CSA or FK-506 in our institution with the same clinical definition for TMA. TMA was diagnosed in 11 of 55 patients (CSA, 3 of 24; FK-506, 8 of 31). RESULTS: The daily risk of developing TMA was 0.12 percent for patients receiving CSA and 0.26 percent for those receiving FK-506 (p = 0.16, chi-square). Among patients receiving FK-506, sibling donor BMT recipients were as likely to develop TMA as matched unrelated donor recipients. Serum CSA and FK-506 concentrations were not elevated above the therapeutic range in most patients with TMA. The blood urea nitrogen to serumcreatinine ratio was elevated in patients with TMA. Despite daily plasmapheresis, 9 of 11 patients died without resolution of TMA; however, the causes of death were multifactorial, including GVHD. Histologic evidence for TMA was absent in 1 patient who died with persistent clinical signs attributed to microangiopathy. CONCLUSIONS: In this study, a high incidence of TMA was found in patients receiving either CSA or FK-506 following BMT, with uniform diagnostic criteria and strict monitoring. Neither drug showed elevated levels in most patients with TMA. Plasmapheresis was unsuccessful in reversing most cases of TMA.