title: Risk factors for thrombotic microangiopathy in allogeneic hematopoietic stem cell recipients receiving GVHD prophylaxis with tacrolimus plus MTX or sirolimus.
abstract: Transplantation-associated thrombotic microangiopathy (TA-TMA) is a feared complication of allogeneic hematopoietic SCT (HSCT) owing to its high mortality rate. The use of calcineurin inhibitors or sirolimus (SIR) for GVHD prophylaxis has been suggested as a potential risk factor. However, the impact of tacrolimus (TAC) and SIR combinations on the increased risk of TA-TMA is currently not well defined. We retrospectively analyzed the incidence of TA-TMA in 102 allogeneic HSCT recipients who consecutively received TAC plus SIR (TAC/SIR) (n=68) or plus MTX (TAC/MTX)±ATG (n=34) for GVHD prophylaxis. No significant differences were observed in the incidence of TA-TMA between patients receiving TAC/SIR vs TAC/MTX±ATG (7.4% vs 8.8%, P=0.8). Only grade III-IV acute GVHD, previous HSCT and serum levels of TAC >25 ng/mL were associated with a greater risk of TA-TMA. Patients developing TA-TMA have significantly poorer survival (P<0.001); however, TA-TMA ceased to be an independent prognostic factor when it was included in a multivariate model. In conclusion, the combination of TAC/SIR does not appear to pose a higher risk of TA-TMA. By contrast, we identified three different risk groups for developing TA-TMA.
authors.affiliation: 1] Department of Hematology, Hospital Universitario de Salamanca, Instituto de Investigación Biomédica de Salamanca (IBSAL), Salamanca, Spain [2] Centro de Investigación del Cáncer, IBMC/CSIC-USAL, Salamanca, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Labrador
authors.affiliation: Department of Hematology, Hospital Universitario de Salamanca, Instituto de Investigación Biomédica de Salamanca (IBSAL), Salamanca, Spain.
authors.forename: L
authors.initials: L
authors.lastname: López-Corral
authors.affiliation: Department of Hematology, Hospital Universitario de Salamanca, Instituto de Investigación Biomédica de Salamanca (IBSAL), Salamanca, Spain.
authors.forename: O
authors.initials: O
authors.lastname: López-Godino
authors.affiliation: Department of Hematology, Hospital Universitario de Salamanca, Instituto de Investigación Biomédica de Salamanca (IBSAL), Salamanca, Spain.
authors.forename: L
authors.initials: L
authors.lastname: Vázquez
authors.affiliation: Department of Hematology, Hospital Universitario de Salamanca, Instituto de Investigación Biomédica de Salamanca (IBSAL), Salamanca, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Cabrero-Calvo
authors.affiliation: Pharmacy Department, Hospital Universitario de Salamanca, Salamanca, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Pérez-López
authors.affiliation: Department of Hematology, Hospital Universitario de Salamanca, Instituto de Investigación Biomédica de Salamanca (IBSAL), Salamanca, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Díez-Campelo
authors.affiliation: Department of Hematology, Hospital Universitario de Salamanca, Instituto de Investigación Biomédica de Salamanca (IBSAL), Salamanca, Spain.
authors.forename: F
authors.initials: F
authors.lastname: Sánchez-Guijo
authors.affiliation: Department of Hematology, Hospital Universitario de Salamanca, Instituto de Investigación Biomédica de Salamanca (IBSAL), Salamanca, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Pérez-López
authors.affiliation: Centro de Investigación del Cáncer, IBMC/CSIC-USAL, Salamanca, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Guerrero
authors.affiliation: Department of Hematology, Hospital Universitario de Salamanca, Instituto de Investigación Biomédica de Salamanca (IBSAL), Salamanca, Spain.
authors.forename: I
authors.initials: I
authors.lastname: Alberca
authors.affiliation: 1] Department of Hematology, Hospital Universitario de Salamanca, Instituto de Investigación Biomédica de Salamanca (IBSAL), Salamanca, Spain [2] Centro de Investigación del Cáncer, IBMC/CSIC-USAL, Salamanca, Spain.
authors.forename: M C
authors.initials: MC
authors.lastname: Del Cañizo
authors.affiliation: Department of Hematology, Hospital Universitario/Instituto de Biomedicina (IBIS)/CSIC, Seville, Spain.
authors.forename: J A
authors.initials: JA
authors.lastname: Pérez-Simón
authors.affiliation: Department of Hematology, Hospital Universitario de Salamanca, Instituto de Investigación Biomédica de Salamanca (IBSAL), Salamanca, Spain.
authors.forename: J R
authors.initials: JR
authors.lastname: González-Porras
authors.affiliation: Department of Hematology, Hospital Universitario de Salamanca, Instituto de Investigación Biomédica de Salamanca (IBSAL), Salamanca, Spain.
authors.forename: D
authors.initials: D
authors.lastname: Caballero
mesh_terms: D000328:Adult; D000368:Aged; D004359:Drug Therapy, Combination; D005260:Female; D006086:Graft vs Host Disease / Q000188:drug therapy / Q000453:epidemiology / Q000517:prevention & control*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects* / Q000706:statistics & numerical data; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000097:blood; D015994:Incidence; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage* / Q000097:blood; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D012189:Retrospective Studies; D012307:Risk Factors; D020123:Sirolimus / Q000008:administration & dosage* / Q000097:blood; D016559:Tacrolimus / Q000008:administration & dosage* / Q000097:blood; D057049:Thrombotic Microangiopathies / Q000453:epidemiology / Q000209:etiology*; D014184:Transplantation, Homologous; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; D020123:Sirolimus; D016559:Tacrolimus; D008727:Methotrexate