title: Transplantation-Associated Thrombotic Microangiopathy in Patients Treated With Sirolimus and Cyclosporine as Salvage Therapy for Graft-Versus-Host Disease.
abstract: BACKGROUND
  Transplantation-associated thrombotic microangiopathy (TA-TMA) is a rare complication of hematopoietic stem cell transplantation. Because sirolimus (SIR) and calcineurin inhibitor-either cyclosporine (CsA) or tacrolimus-have become more common as graft-versus-host disease (GVHD) prophylaxis, we are witnessing a higher frequency of this complication.
  
  
  OBJECTIVE
  To analyze the incidence, timing, and management of TA-TMA in patients who received the combination of CsA and SIR as therapy for uncontrolled GVHD in one single center.
  
  
  METHODS
  This was a retrospective analysis from February 2002 to June 2014 of the combination of SIR and CsA as salvage therapy in 61 patients with treatment-refractory or relapsed acute GVHD (n = 24) or chronic GVHD (n = 37) in a tertiary hospital.
  
  
  RESULTS
  A total of 61 patients received CsA and SIR as salvage therapy for acute (n = 16), late acute (n = 8), overlap syndrome (n = 22), or classic chronic (n = 15) GVHD. We identified 13 patients with TA-TMA (21.3%), and the status of GVHD was active in 11 of 13 patients. Only 1 patient showed high CsA levels, and 6 of 13 patients had very high concentrations of SIR in blood. We used an enzyme inducer in 6 patients, which proved effective in 3. Overall survival for TA-TMA patients was inferior compared to that for non TA-TMA patients at 12 months (42.9% vs 51.9%) and 24 months (34.3% vs 49.1%), although this difference was not significant.
  
  
  CONCLUSIONS
  Prompt identification and good management of TA-TMA, with better control of GVHD, may contribute to a decrease in patient mortality that would result from this complication.
authors.affiliation: Department of Hematology, Hospital Universitario Virgen de las Nieves, Granada, Spain.
authors.forename: Paloma
authors.initials: P
authors.lastname: García-Martín
authors.affiliation: Department of Pharmacy, Hospital Univeristario Virgen de las Nieves, Granada, Spain carolina.alarcon.sspa@juntadeandalucia.es.
authors.forename: Carolina
authors.initials: C
authors.lastname: Alarcón-Payer
authors.affiliation: Department of Hematology, Hospital Universitario Virgen de las Nieves, Granada, Spain.
authors.forename: Elisa
authors.initials: E
authors.lastname: López-Fernández
authors.affiliation: Department of Hematology, Hospital Universitario Virgen de las Nieves, Granada, Spain.
authors.forename: Lucía
authors.initials: L
authors.lastname: Moratalla
authors.affiliation: Department of Hematology, Hospital Universitario Virgen de las Nieves, Granada, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Romero
authors.affiliation: Department of Hematology, Hospital Universitario Virgen de las Nieves, Granada, Spain Genyo, Pfizer-University of Granada-Junta de Andalucía, Granada, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Sainz
authors.affiliation: Department of Hematology, Hospital Universitario Virgen de las Nieves, Granada, Spain Genyo, Pfizer-University of Granada-Junta de Andalucía, Granada, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Ríos
authors.affiliation: Department of Hematology, Hospital Universitario Virgen de las Nieves, Granada, Spain Genyo, Pfizer-University of Granada-Junta de Andalucía, Granada, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Jurado
mesh_terms: D000208:Acute Disease; D000328:Adult; D065095:Calcineurin Inhibitors / Q000627:therapeutic use*; D002908:Chronic Disease; D016572:Cyclosporine / Q000627:therapeutic use*; D005260:Female; D006086:Graft vs Host Disease / Q000188:drug therapy* / Q000401:mortality; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D015994:Incidence; D008297:Male; D012008:Recurrence; D012189:Retrospective Studies; D016879:Salvage Therapy; D020123:Sirolimus / Q000627:therapeutic use*; D057049:Thrombotic Microangiopathies / Q000188:drug therapy* / Q000209:etiology / Q000401:mortality
chemical_list: D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D020123:Sirolimus
keywords: cyclosporine; hematology; immunosuppressants; prophylaxis; transplants