PMID- 33908301
OWN - NLM
STAT- MEDLINE
DCOM- 20211117
LR  - 20231111
IS  - 1555-3892 (Electronic)
IS  - 0963-6897 (Print)
IS  - 0963-6897 (Linking)
VI  - 30
DP  - 2021 Jan-Dec
TI  - Post-Hoc Analysis of a Randomized, Double Blind, Prospective Study at the 
      University of Chicago: Additional Standardizations of Trial Protocol are Needed 
      to Evaluate the Effect of a CXCR1/2 Inhibitor in Islet Allotransplantation.
PG  - 9636897211001774
LID - 10.1177/09636897211001774 [doi]
LID - 09636897211001774
AB  - A recent randomized, multicenter trial did not show benefit of a CXCR1/2 receptor 
      inhibitor (Reparixin) when analysis included marginal islet mass (>3,000 IEQ/kg) 
      for allotransplantation and when immunosuppression regimens were not standardized 
      among participating centers. We present a post-hoc analysis of trial patients 
      from our center at the University of Chicago who received an islet mass of over 
      5,000 IEQ/kg and a standardized immunosuppression regimen of anti-thymocyte 
      globulin (ATG) for induction. Twelve islet allotransplantation (ITx) recipients 
      were randomized (2:1) to receive Reparixin (N = 8) or placebo (N = 4) in 
      accordance with the multicenter trial protocol. Pancreas and donor 
      characteristics did not differ between Reparixin and placebo groups. Five (62.5%) 
      patients who received Reparixin, compared to none in the placebo group, achieved 
      insulin independence after only one islet infusion and remained insulin-free for 
      over 2 years (P = 0.08). Following the first ITx with ATG induction, distinct 
      cytokine, chemokine, and miR-375 release profiles were observed for both the 
      Reparixin and placebo groups. After excluding procedures with complications, 
      islet engraftment on post-operative day 75 after a single transplant was higher 
      in the Reparixin group (n = 7) than in the placebo (n = 3) group (P = 0.03) when 
      islet graft function was measured by the ratio of the area under the curve (AUC) 
      for c-peptide to glucose in mixed meal tolerance test (MMTT). Additionally, the 
      rate of engraftment was higher when determined via BETA-2 score instead of MMTT 
      (P = 0.01). Our analysis suggests that Reparixin may have improved outcomes 
      compared to placebo when sufficient islet mass is transplanted and when 
      standardized immunosuppression with ATG is used for induction. However, further 
      studies are warranted. Investigation of Reparixin and other novel agents under 
      more standardized and optimized conditions would help exclude confounding factors 
      and allow for a more definitive evaluation of their role in improving outcomes in 
      islet transplantation. Clinical trial reg. no. NCT01817959, clinicaltrials.gov.
FAU - Bachul, Piotr J
AU  - Bachul PJ
AUID- ORCID: 0000-0002-7694-1793
AD  - Department of Surgery, The Transplantation Institute, 2462University of Chicago, 
      Chicago, IL, USA.
FAU - Golab, Karolina
AU  - Golab K
AD  - Department of Surgery, The Transplantation Institute, 2462University of Chicago, 
      Chicago, IL, USA.
FAU - Basto, Lindsay
AU  - Basto L
AD  - Department of Surgery, The Transplantation Institute, 2462University of Chicago, 
      Chicago, IL, USA.
FAU - Zangan, Steven
AU  - Zangan S
AD  - Department of Radiology, 2462University of Chicago, Chicago, IL, USA.
FAU - Pyda, Jordan S
AU  - Pyda JS
AUID- ORCID: 0000-0002-2833-3953
AD  - Department of Surgery, Beth Israel Deaconess Medical Center, Boston, MA, USA.
FAU - Perez-Gutierrez, Angelica
AU  - Perez-Gutierrez A
AD  - Department of Surgery, The Transplantation Institute, 2462University of Chicago, 
      Chicago, IL, USA.
FAU - Borek, Peter
AU  - Borek P
AD  - Department of Surgery, The Transplantation Institute, 2462University of Chicago, 
      Chicago, IL, USA.
FAU - Wang, Ling-Jia
AU  - Wang LJ
AD  - Department of Surgery, The Transplantation Institute, 2462University of Chicago, 
      Chicago, IL, USA.
FAU - Tibudan, Martin
AU  - Tibudan M
AD  - Department of Surgery, The Transplantation Institute, 2462University of Chicago, 
      Chicago, IL, USA.
FAU - Tran, Dong-Kha
AU  - Tran DK
AD  - Department of Surgery, The Transplantation Institute, 2462University of Chicago, 
      Chicago, IL, USA.
FAU - Anteby, Roi
AU  - Anteby R
AD  - Department of Surgery, The Transplantation Institute, 2462University of Chicago, 
      Chicago, IL, USA.
FAU - Generette, Gabriela S
AU  - Generette GS
AD  - Department of Surgery, The Transplantation Institute, 2462University of Chicago, 
      Chicago, IL, USA.
FAU - Chrzanowski, Jedrzej
AU  - Chrzanowski J
AD  - Department of Biostatistics and Translational Medicine, 37808Medical University 
      of Lodz, Lodz, Poland.
FAU - Fendler, Wojciech
AU  - Fendler W
AD  - Department of Biostatistics and Translational Medicine, 37808Medical University 
      of Lodz, Lodz, Poland.
FAU - Perea, Laurencia
AU  - Perea L
AD  - Department of Surgery, The Transplantation Institute, 2462University of Chicago, 
      Chicago, IL, USA.
FAU - Jayant, Kumar
AU  - Jayant K
AD  - Department of Surgery, The Transplantation Institute, 2462University of Chicago, 
      Chicago, IL, USA.
FAU - Lucander, Aaron
AU  - Lucander A
AD  - Department of Surgery, The Transplantation Institute, 2462University of Chicago, 
      Chicago, IL, USA.
FAU - Thomas, Celeste
AU  - Thomas C
AD  - Department of Medicine, University of Chicago, Chicago, IL, USA.
FAU - Philipson, Louis
AU  - Philipson L
AD  - Department of Medicine, University of Chicago, Chicago, IL, USA.
FAU - Millis, J Michael
AU  - Millis JM
AD  - Department of Surgery, The Transplantation Institute, 2462University of Chicago, 
      Chicago, IL, USA.
FAU - Fung, John
AU  - Fung J
AD  - Department of Surgery, The Transplantation Institute, 2462University of Chicago, 
      Chicago, IL, USA.
FAU - Witkowski, Piotr
AU  - Witkowski P
AUID- ORCID: 0000-0002-4459-6673
AD  - Department of Surgery, The Transplantation Institute, 2462University of Chicago, 
      Chicago, IL, USA.
LA  - eng
SI  - ClinicalTrials.gov/NCT01817959
GR  - P30 DK020595/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cell Transplant
JT  - Cell transplantation
JID - 9208854
RN  - 0 (Immunosuppressive Agents)
SB  - IM
MH  - Adult
MH  - Animals
MH  - Chicago
MH  - Double-Blind Method
MH  - Female
MH  - Humans
MH  - Immunosuppressive Agents/pharmacology/*therapeutic use
MH  - Islets of Langerhans Transplantation/*methods
MH  - Male
MH  - Mice
MH  - Mice, Nude
MH  - Middle Aged
MH  - Prospective Studies
MH  - United States
MH  - Vascularized Composite Allotransplantation/*methods
PMC - PMC8085379
OTO - NOTNLM
OT  - Islet transplantation
OT  - chemokine receptors
OT  - chemokines
OT  - immune modulation
OT  - immunosuppressive regimens
OT  - induction
COIS- Declaration of Conflicting Interests: P.W. served as a co-PI in another 
      multi-center trial in islet auto-transplantation and as a consultant for Dompe 
      farmaceutici S.p.A. in another study involving liver transplantation. The 
      author(s) declared no other potential conflicts of interest with respect to the 
      research, authorship, and/or publication of this article.
EDAT- 2021/04/29 06:00
MHDA- 2021/11/18 06:00
PMCR- 2021/04/28
CRDT- 2021/04/28 08:42
PHST- 2021/04/28 08:42 [entrez]
PHST- 2021/04/29 06:00 [pubmed]
PHST- 2021/11/18 06:00 [medline]
PHST- 2021/04/28 00:00 [pmc-release]
AID - 10.1177_09636897211001774 [pii]
AID - 10.1177/09636897211001774 [doi]
PST - ppublish
SO  - Cell Transplant. 2021 Jan-Dec;30:9636897211001774. doi: 
      10.1177/09636897211001774.