PMID- 31070229
OWN - NLM
STAT- MEDLINE
DCOM- 20200326
LR  - 20200326
IS  - 1462-0332 (Electronic)
IS  - 1462-0324 (Print)
IS  - 1462-0324 (Linking)
VI  - 58
IP  - 10
DP  - 2019 Oct 1
TI  - Bone-marrow derived mesenchymal stromal cells infusion in therapy refractory 
      juvenile idiopathic arthritis patients.
PG  - 1812-1817
LID - 10.1093/rheumatology/kez157 [doi]
AB  - OBJECTIVES: To compare the total number of adverse events (AEs) before and after 
      mesenchymal stromal cell (MSC) infusion in refractory JIA and to evaluate its 
      effectiveness. METHODS: Single-centre Proof of Mechanism Phase Ib, open label 
      intervention study in JIA patients previously failing all biologicals registered 
      for their diagnosis. Six patients received 2 million/kg intravenous infusions of 
      allogeneic bone-marrow derived MSC. In case of ACR-Ped30-response but subsequent 
      loss of response one and maximal two repeated infusions are allowed. RESULTS: Six 
      JIA patients with 9.2 years median disease duration, still active arthritis and 
      damage were included. All had failed methotrexate, corticosteroids and median 
      five different biologicals. MSC were administered twice in three patients. No 
      acute infusion reactions were observed and a lower post-treatment than 
      pre-treatment incidence in AEs was found. The one systemic onset JIA (sJIA) 
      patient had again an evolving macrophage activation syndrome, 9 weeks after 
      tocilizumab discontinuation and 7 weeks post-MSC infusion. Statistically 
      significant decreases were found 8 weeks after one MSC infusion in VAS well-being 
      (75-56), the JADAS-71 (24.5-11.0) and the cJADAS10 (18.0-10.6). CONCLUSION: MSC 
      infusions in six refractory JIA patients were safe, although in sJIA stopping the 
      'failing' biologic treatment carries a risk of a MAS flare, as the drug might 
      still suppress the systemic features. TRIAL REGISTRATION: Trial register.nl, 
      http://https://www.trialregister.nl, NTR4146.
CI  - (c) The Author(s) 2019. Published by Oxford University Press on behalf of the 
      British Society for Rheumatology.
FAU - Swart, Joost F
AU  - Swart JF
AD  - Department of Pediatric Immunology and Rheumatology, UMC Utrecht, Wilhelmina 
      Children's Hospital.
AD  - Faculty of Medicine, Utrecht University.
FAU - de Roock, Sytze
AU  - de Roock S
AD  - Department of Pediatric Immunology and Rheumatology, UMC Utrecht, Wilhelmina 
      Children's Hospital.
AD  - Faculty of Medicine, Utrecht University.
FAU - Nievelstein, Rutger A J
AU  - Nievelstein RAJ
AD  - Faculty of Medicine, Utrecht University.
AD  - Department of Pediatric Radiology, Division Imaging, UMC Utrecht, Utrecht, The 
      Netherlands.
FAU - Slaper-Cortenbach, Ineke C M
AU  - Slaper-Cortenbach ICM
AD  - Cell Therapy Facility, Division Laboratories and Pharmacy, UMC Utrecht, Utrecht, 
      The Netherlands.
FAU - Boelens, Jaap J
AU  - Boelens JJ
AD  - Department of Pediatric Immunology and Rheumatology, UMC Utrecht, Wilhelmina 
      Children's Hospital.
AD  - Faculty of Medicine, Utrecht University.
FAU - Wulffraat, Nico M
AU  - Wulffraat NM
AD  - Department of Pediatric Immunology and Rheumatology, UMC Utrecht, Wilhelmina 
      Children's Hospital.
AD  - Faculty of Medicine, Utrecht University.
LA  - eng
SI  - NTR/NTR4146
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Rheumatology (Oxford)
JT  - Rheumatology (Oxford, England)
JID - 100883501
SB  - IM
MH  - Adolescent
MH  - Arthritis, Juvenile/*therapy
MH  - *Bone Marrow Cells
MH  - Child
MH  - Female
MH  - Humans
MH  - Infusions, Intravenous
MH  - Male
MH  - Mesenchymal Stem Cell Transplantation/*methods
MH  - *Mesenchymal Stem Cells
MH  - Pilot Projects
MH  - Proof of Concept Study
MH  - Treatment Outcome
PMC - PMC6758577
OTO - NOTNLM
OT  - Juvenile arthritis
OT  - mesenchymal stromal cells
OT  - stem cell transplantation
OT  - therapeutics
EDAT- 2019/05/10 06:00
MHDA- 2020/03/27 06:00
PMCR- 2019/04/27
CRDT- 2019/05/10 06:00
PHST- 2019/01/07 00:00 [received]
PHST- 2019/03/25 00:00 [revised]
PHST- 2019/05/10 06:00 [pubmed]
PHST- 2020/03/27 06:00 [medline]
PHST- 2019/05/10 06:00 [entrez]
PHST- 2019/04/27 00:00 [pmc-release]
AID - 5481137 [pii]
AID - kez157 [pii]
AID - 10.1093/rheumatology/kez157 [doi]
PST - ppublish
SO  - Rheumatology (Oxford). 2019 Oct 1;58(10):1812-1817. doi: 
      10.1093/rheumatology/kez157.