Islet Allotransplantation in the Bone Marrow of Patients With Type 1 Diabetes: A Pilot Randomized Trial

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Abstract

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.

Original languageEnglish
Pages (from-to)839-851
Number of pages13
JournalTransplantation
Volume103
Issue number4
DOIs
Publication statusPublished - Apr 1 2019

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Type 1 Diabetes Mellitus
Bone Marrow
Islets of Langerhans Transplantation
Homologous Transplantation
Liver
Transplants
Biopsy
C-Peptide
Feasibility Studies
Autoimmunity
Islets of Langerhans
Primates
Insulin
Recurrence
Injections
Survival

ASJC Scopus subject areas

  • Transplantation

Cite this

@article{faee06a2090548f190d536b5ec5f0912,
title = "Islet Allotransplantation in the Bone Marrow of Patients With Type 1 Diabetes: A Pilot Randomized Trial",
abstract = "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.",
author = "Paola Maffi and Rita Nano and Paolo Monti and Raffaella Melzi and Valeria Sordi and Alessia Mercalli and Silvia Pellegrini and Maurilio Ponzoni and Jacopo Peccatori and Carlo Messina and Angela Nocco and Massimo Cardillo and Marina Scavini and Paola Magistretti and Claudio Doglioni and Fabio Ciceri and Bloem, {Stef J.} and Roep, {Bart O.} and Antonio Secchi and Lorenzo Piemonti",
year = "2019",
month = "4",
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doi = "10.1097/TP.0000000000002416",
language = "English",
volume = "103",
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journal = "Transplantation",
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TY - JOUR

T1 - Islet Allotransplantation in the Bone Marrow of Patients With Type 1 Diabetes

T2 - A Pilot Randomized Trial

AU - Maffi, Paola

AU - Nano, Rita

AU - Monti, Paolo

AU - Melzi, Raffaella

AU - Sordi, Valeria

AU - Mercalli, Alessia

AU - Pellegrini, Silvia

AU - Ponzoni, Maurilio

AU - Peccatori, Jacopo

AU - Messina, Carlo

AU - Nocco, Angela

AU - Cardillo, Massimo

AU - Scavini, Marina

AU - Magistretti, Paola

AU - Doglioni, Claudio

AU - Ciceri, Fabio

AU - Bloem, Stef J.

AU - Roep, Bart O.

AU - Secchi, Antonio

AU - Piemonti, Lorenzo

PY - 2019/4/1

Y1 - 2019/4/1

N2 - 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.

AB - 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.

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DO - 10.1097/TP.0000000000002416

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VL - 103

SP - 839

EP - 851

JO - Transplantation

JF - Transplantation

SN - 0041-1337

IS - 4

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