Alemtuzumab Induction and Delayed Acute Rejection in Steroid-Free Simultaneous Pancreas-Kidney Transplant Recipients.

Autor:	Bank JR; Department of Nephrology, Leiden University Medical Center, The Netherlands., Heidt S; Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, The Netherlands., Moes DJ; Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, The Netherlands., Roelen DL; Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, The Netherlands., Mallat MJ; Department of Nephrology, Leiden University Medical Center, The Netherlands., van der Boog PJ; Department of Nephrology, Leiden University Medical Center, The Netherlands., Vergunst M; Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, The Netherlands., Jol-van der Zijde CM; Department of Pediatrics, Leiden University Medical Center, The Netherlands., Bredius RG; Department of Pediatrics, Leiden University Medical Center, The Netherlands., Braat AE; Department of Transplant Surgery, Leiden University Medical Center, The Netherlands., Ringers J; Department of Transplant Surgery, Leiden University Medical Center, The Netherlands., van Tol MJ; Department of Pediatrics, Leiden University Medical Center, The Netherlands., Claas FH; Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, The Netherlands., Reinders ME; Department of Nephrology, Leiden University Medical Center, The Netherlands., de Fijter JW; Department of Nephrology, Leiden University Medical Center, The Netherlands.
Jazyk:	angličtina
Zdroj:	Transplantation direct [Transplant Direct] 2016 Dec 19; Vol. 3 (1), pp. e124. Date of Electronic Publication: 2016 Dec 19 (Print Publication: 2017).
DOI:	10.1097/TXD.0000000000000634
Abstrakt:	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. Competing Interests: The authors declare no conflicts of interest.
Databáze:	MEDLINE
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