title: Eculizumab in Transplant-Associated Thrombotic Microangiopathy.
abstract: BACKGROUND
  Transplant-associated thrombotic microangiopathy (TA-TMA) is a rare entity with no standard of care and high mortality, despite the use of plasma exchange.
  
  
  METHODS
  Using specific search terms, all cases having TA-TMA treated with eculizumab and indexed in MEDLINE (English language only) by November 2014 were reviewed.
  
  
  RESULTS
  A total of 26 cases, 53% men, had a median age of 33 years (range 2-61). Transplant-associated thrombotic microangiopathy occurred after stem-cell transplant (35%) or solid-organ transplant (65%), frequently associated with the use of cyclosporine or tacrolimus (96%). A disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS 13) level was always >10%. After TA-TMA diagnosis, the following drug adjustments were made: discontinuation of cyclosporine or tacrolimus in 45%, dose reduction in another 27%, continuation of the drugs in 23%, and switch from cyclosporine to tacrolimus in remaining 5%. Plasma exchange was performed in ∼43%. The median interval between transplant and initiation of eculizumab was 63 days (range 11-512). A median of 5.5 doses (range 2-21) of eculizumab was utilized with 92% response occurring after a median of 2 doses (range 1-18). At a median follow-up of 52 weeks (range 3-113), the survivors (92%) were doing well.
  
  
  CONCLUSIONS
  Within the limits of this retrospective analysis, our study demonstrates that eculizumab use may result in high response rate and 1-year survival in patients with TA-TMA refractory to discontinuation of calcineurin inhibitor and plasma exchange.
authors.affiliation: 1 Department of Medicine, Institute of Medicine, Tribhuvan University, Kathmandu, Nepal.
authors.forename: Prajwal
authors.initials: P
authors.lastname: Dhakal
authors.affiliation: 2 Department of Medicine, University of Tennessee Health Science Center, Memphis, TN, USA.
authors.forename: Smith
authors.initials: S
authors.lastname: Giri
authors.affiliation: 3 Department of Medicine, Reading Health System, West Reading, PA, USA.
authors.forename: Ranjan
authors.initials: R
authors.lastname: Pathak
authors.affiliation: 4 Department of Internal Medicine, Division of Hematology-Oncology, University of Nebraska Medical Center, Omaha, NE, USA.
authors.forename: Vijaya Raj
authors.initials: VR
authors.lastname: Bhatt
mesh_terms: D000293:Adolescent; D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D016572:Cyclosporine; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016377:Organ Transplantation; D010951:Plasma Exchange; D012189:Retrospective Studies; D033581:Stem Cell Transplantation; D015996:Survival Rate; D016559:Tacrolimus; D057049:Thrombotic Microangiopathies / Q000209:etiology* / Q000401:mortality / Q000517:prevention & control; D014180:Transplantation / Q000009:adverse effects*; D055815:Young Adult
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D016572:Cyclosporine; C481642:eculizumab; D016559:Tacrolimus
keywords: calcineurin inhibitors; eculizumab; solid-organ transplant; stem cell transplant; thrombotic microangiopathy