Islet Allotransplantation in the Bone Marrow of Patients With Type 1 Diabetes: A Pilot Randomized Trial.
Journal
Transplantation
ISSN: 1534-6080
Titre abrégé: Transplantation
Pays: United States
ID NLM: 0132144
Informations de publication
Date de publication:
04 2019
04 2019
Historique:
pubmed:
22
8
2018
medline:
31
8
2019
entrez:
22
8
2018
Statut:
ppublish
Résumé
Results in murine and nonhuman primate suggested that the bone marrow (BM) might be an alternative site for pancreatic islet transplantation. We report the results of 2 clinical studies in patients with type 1 diabetes receiving an intra-BM allogeneic islet transplantation: a feasibility study in patients with hepatic contraindications for liver islet allotransplantation receiving a single intra-BM islet infusion (n = 4) and a pilot randomized trial (1:1 allocation using blocks of size 6) in which patients were randomized to receive islets into either the liver (n = 6) or BM (n = 3) to evaluate islet transplant function and survival. We observed no adverse events related to the intrabone injection procedure or the presence of islets in the BM. None of the recipient of an intra-BM allogeneic islet transplantation had a primary nonfunction, as shown by measurable posttransplantation C-peptide levels and histopathological evidence of insulin-producing cells or molecular markers of endocrine tissue in BM biopsy samples collected during follow-up. All patients receiving islets in the BM except 1 lost islet function during the first 4 months after infusion (2 with an early graft loss). Based on biopsies and immunomonitoring, we concluded that the islet loss was primarily caused by the recurrence of autoimmunity. Bone marrow is not a suitable alternative site for pancreatic islet allotransplantation in patients with type 1 diabetes.
Sections du résumé
BACKGROUND
Results in murine and nonhuman primate suggested that the bone marrow (BM) might be an alternative site for pancreatic islet transplantation.
METHODS
We report the results of 2 clinical studies in patients with type 1 diabetes receiving an intra-BM allogeneic islet transplantation: a feasibility study in patients with hepatic contraindications for liver islet allotransplantation receiving a single intra-BM islet infusion (n = 4) and a pilot randomized trial (1:1 allocation using blocks of size 6) in which patients were randomized to receive islets into either the liver (n = 6) or BM (n = 3) to evaluate islet transplant function and survival.
RESULTS
We observed no adverse events related to the intrabone injection procedure or the presence of islets in the BM. None of the recipient of an intra-BM allogeneic islet transplantation had a primary nonfunction, as shown by measurable posttransplantation C-peptide levels and histopathological evidence of insulin-producing cells or molecular markers of endocrine tissue in BM biopsy samples collected during follow-up. All patients receiving islets in the BM except 1 lost islet function during the first 4 months after infusion (2 with an early graft loss). Based on biopsies and immunomonitoring, we concluded that the islet loss was primarily caused by the recurrence of autoimmunity.
CONCLUSIONS
Bone marrow is not a suitable alternative site for pancreatic islet allotransplantation in patients with type 1 diabetes.
Identifiants
pubmed: 30130323
doi: 10.1097/TP.0000000000002416
doi:
Banques de données
ClinicalTrials.gov
['NCT01345227', 'NCT01722682']
Types de publication
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM