title: Alemtuzumab Induction and Delayed Acute Rejection in Steroid-Free Simultaneous Pancreas-Kidney Transplant Recipients.
abstract: BACKGROUND
  The optimal immunosuppressive regimen in simultaneous pancreas-kidney transplant (SPKT) recipients that prevents acute rejection episodes (AREs) and allows optimal outcome remains elusive.
  
  
  METHODS
  This cohort study assessed incidence and time to AREs in 73 consecutive SPKT recipients receiving alemtuzumab induction and steroid-free maintenance with tacrolimus and mycophenolate mofetil. A cohort with single high-dose antithymocyte globulin (ATG; n = 85) and triple therapy served as controls. In addition, we provided mechanistic insights in AREs after alemtuzumab depletion, including composition and alloreactivity of lymphocytes (flow cytometry and mixed lymphocyte reaction) plasma alemtuzumab levels (enzyme-linked immunosorbent assay), and maintenance drug exposure.
  
  
  RESULTS
  Overall number of AREs at 3 years was significantly lower with alemtuzumab versus ATG induction (26.0% vs 43.5%; adjusted hazard ratio, 0.38;P= 0.029). Most AREs (94.6%) with ATG occurred within the first month, whereas 84.2% of AREs with alemtuzumab occurred beyond 3 months. Patients with and without an ARE in the steroid-free alemtuzumab group showed no differences in composition of lymphocytes, or in alemtuzumab levels. Of note, more than two thirds of these AREs were preceded by empiric tacrolimus and/or mycophenolate mofetil dose adjustments due to viral infections, leukopenia, or gastrointestinal symptoms.
  
  
  CONCLUSIONS
  Alemtuzumab induction resulted in a significant lower incidence of AREs. Empiric dose adjustments beyond 3 months in the absence of steroids carry a significant risk for subsequent rejection in SPKT recipients.
authors.affiliation: Department of Nephrology, Leiden University Medical Center, The Netherlands.
authors.forename: Jonna R
authors.initials: JR
authors.lastname: Bank
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, The Netherlands.
authors.forename: Sebastiaan
authors.initials: S
authors.lastname: Heidt
authors.affiliation: Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, The Netherlands.
authors.forename: Dirk Jan A R
authors.initials: DJ
authors.lastname: Moes
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, The Netherlands.
authors.forename: Dave L
authors.initials: DL
authors.lastname: Roelen
authors.affiliation: Department of Nephrology, Leiden University Medical Center, The Netherlands.
authors.forename: Marko J K
authors.initials: MJ
authors.lastname: Mallat
authors.affiliation: Department of Nephrology, Leiden University Medical Center, The Netherlands.
authors.forename: Paul J M
authors.initials: PJ
authors.lastname: van der Boog
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, The Netherlands.
authors.forename: Manon
authors.initials: M
authors.lastname: Vergunst
authors.affiliation: Department of Pediatrics, Leiden University Medical Center, The Netherlands.
authors.forename: Cornelia M
authors.initials: CM
authors.lastname: Jol-van der Zijde
authors.affiliation: Department of Pediatrics, Leiden University Medical Center, The Netherlands.
authors.forename: Robbert G M
authors.initials: RG
authors.lastname: Bredius
authors.affiliation: Department of Transplant Surgery, Leiden University Medical Center, The Netherlands.
authors.forename: Andries E
authors.initials: AE
authors.lastname: Braat
authors.affiliation: Department of Transplant Surgery, Leiden University Medical Center, The Netherlands.
authors.forename: Jan
authors.initials: J
authors.lastname: Ringers
authors.affiliation: Department of Pediatrics, Leiden University Medical Center, The Netherlands.
authors.forename: Maarten J D
authors.initials: MJ
authors.lastname: van Tol
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, The Netherlands.
authors.forename: Frans H J
authors.initials: FH
authors.lastname: Claas
authors.affiliation: Department of Nephrology, Leiden University Medical Center, The Netherlands.
authors.forename: Marlies E J
authors.initials: ME
authors.lastname: Reinders
authors.affiliation: Department of Nephrology, Leiden University Medical Center, The Netherlands.
authors.forename: Johannes W
authors.initials: JW
authors.lastname: de Fijter