PMID- 28349124
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201001
IS  - 2373-8731 (Print)
IS  - 2373-8731 (Electronic)
IS  - 2373-8731 (Linking)
VI  - 3
IP  - 1
DP  - 2017 Jan
TI  - Alemtuzumab Induction and Delayed Acute Rejection in Steroid-Free Simultaneous 
      Pancreas-Kidney Transplant Recipients.
PG  - e124
LID - 10.1097/TXD.0000000000000634 [doi]
LID - e124
AB  - 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.
FAU - Bank, Jonna R
AU  - Bank JR
AD  - Department of Nephrology, Leiden University Medical Center, The Netherlands.
FAU - Heidt, Sebastiaan
AU  - Heidt S
AD  - Department of Immunohematology and Blood Transfusion, Leiden University Medical 
      Center, The Netherlands.
FAU - Moes, Dirk Jan A R
AU  - Moes DJ
AD  - Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, 
      The Netherlands.
FAU - Roelen, Dave L
AU  - Roelen DL
AD  - Department of Immunohematology and Blood Transfusion, Leiden University Medical 
      Center, The Netherlands.
FAU - Mallat, Marko J K
AU  - Mallat MJ
AD  - Department of Nephrology, Leiden University Medical Center, The Netherlands.
FAU - van der Boog, Paul J M
AU  - van der Boog PJ
AD  - Department of Nephrology, Leiden University Medical Center, The Netherlands.
FAU - Vergunst, Manon
AU  - Vergunst M
AD  - Department of Immunohematology and Blood Transfusion, Leiden University Medical 
      Center, The Netherlands.
FAU - Jol-van der Zijde, Cornelia M
AU  - Jol-van der Zijde CM
AD  - Department of Pediatrics, Leiden University Medical Center, The Netherlands.
FAU - Bredius, Robbert G M
AU  - Bredius RG
AD  - Department of Pediatrics, Leiden University Medical Center, The Netherlands.
FAU - Braat, Andries E
AU  - Braat AE
AD  - Department of Transplant Surgery, Leiden University Medical Center, The 
      Netherlands.
FAU - Ringers, Jan
AU  - Ringers J
AD  - Department of Transplant Surgery, Leiden University Medical Center, The 
      Netherlands.
FAU - van Tol, Maarten J D
AU  - van Tol MJ
AD  - Department of Pediatrics, Leiden University Medical Center, The Netherlands.
FAU - Claas, Frans H J
AU  - Claas FH
AD  - Department of Immunohematology and Blood Transfusion, Leiden University Medical 
      Center, The Netherlands.
FAU - Reinders, Marlies E J
AU  - Reinders ME
AD  - Department of Nephrology, Leiden University Medical Center, The Netherlands.
FAU - de Fijter, Johannes W
AU  - de Fijter JW
AD  - Department of Nephrology, Leiden University Medical Center, The Netherlands.
LA  - eng
PT  - Journal Article
DEP - 20161219
PL  - United States
TA  - Transplant Direct
JT  - Transplantation direct
JID - 101651609
PMC - PMC5361562
COIS- The authors declare no conflicts of interest.
EDAT- 2017/03/30 06:00
MHDA- 2017/03/30 06:01
PMCR- 2016/12/19
CRDT- 2017/03/29 06:00
PHST- 2016/09/07 00:00 [received]
PHST- 2016/09/13 00:00 [accepted]
PHST- 2017/03/29 06:00 [entrez]
PHST- 2017/03/30 06:00 [pubmed]
PHST- 2017/03/30 06:01 [medline]
PHST- 2016/12/19 00:00 [pmc-release]
AID - TXD50115 [pii]
AID - 10.1097/TXD.0000000000000634 [doi]
PST - epublish
SO  - Transplant Direct. 2016 Dec 19;3(1):e124. doi: 10.1097/TXD.0000000000000634. 
      eCollection 2017 Jan.