title: Thrombotic microangiopathy in blood and marrow transplant patients receiving tacrolimus or cyclosporine A.
abstract: 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.
  
  
  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 serum creatinine 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.
authors.affiliation: Division of Hematology and Oncology, University of Maryland School of Medicine, Baltimore, USA. clarence.adoo@bannerhealth.com
authors.forename: Clarence
authors.initials: C
authors.lastname: Sarkodee-Adoo
authors.forename: Dan
authors.initials: D
authors.lastname: Sotirescu
authors.forename: Lyle
authors.initials: L
authors.lastname: Sensenbrenner
authors.forename: Aaron P
authors.initials: AP
authors.lastname: Rapoport
authors.forename: Michele
authors.initials: M
authors.lastname: Cottler-Fox
authors.forename: Guido
authors.initials: G
authors.lastname: Tricot
authors.forename: Kathy
authors.initials: K
authors.lastname: Ruehle
authors.forename: Barry
authors.initials: B
authors.lastname: Meisenberg
mesh_terms: D000328:Adult; D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D016572:Cyclosporine / Q000009:adverse effects*; D005260:Female; D006086:Graft vs Host Disease / Q000453:epidemiology; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D015994:Incidence; D008297:Male; D008875:Middle Aged; D010956:Plasmapheresis; D012189:Retrospective Studies; D016559:Tacrolimus / Q000009:adverse effects*; D013927:Thrombosis / Q000453:epidemiology / Q000209:etiology* / Q000628:therapy
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine; D016559:Tacrolimus