Lymphocyte reconstitution following autologous stem cell transplantation for progressive MS

Gavin Cull, D. Hall, Marzena J. Fabis-Pedrini, William MacEwan Carroll, Luke Benjamin Forster, Fiona Robins, Reza Ghassemifar, Christina Tran Cameron Crosbie, Susan Elaine Walters, Ian James, Bradley Augustson, Allan G Kermode

Research output: Contribution to journalArticle

Abstract

BACKGROUND: Autologous stem cell transplantation (ASCT) for progressive multiple sclerosis (MS) may reset the immune repertoire.

OBJECTIVE: The objective of this paper is to analyse lymphocyte recovery in patients with progressive MS treated with ASCT.

METHODS: Patients with progressive MS not responding to conventional treatment underwent ASCT following conditioning with high-dose cyclophosphamide and antithymocyte globulin. Lymphocyte subset analysis was performed before ASCT and for two years following ASCT. Neurological function was assessed by the EDSS before ASCT and for three years post-ASCT.

RESULTS: CD4+ T-cells fell significantly post-transplant and did not return to baseline levels. Recent thymic emigrants and naïve T-cells fell sharply post-transplant but returned to baseline by nine months and twelve months, respectively. T-regulatory cells declined post-transplant and did not return to baseline levels. Th1 and Th2 cells did not change significantly while Th17 cells fell post-transplant but recovered to baseline by six months. Neurological function remained stable in the majority of patients. Progression-free survival was 69% at three years.

CONCLUSION: This study demonstrates major changes in the composition of lymphocyte subsets following ASCT for progressive MS. In particular, ablation and subsequent recovery of thymic output is consistent with the concept that ASCT can reset the immune repertoire in MS patients.

Original languageEnglish
Pages (from-to)1-9
JournalMultiple Sclerosis Journal - Experimental, Translational and Clinical
Volume3
Issue number1
DOIs
Publication statusPublished - 14 Jun 2017

Fingerprint

Stem Cell Transplantation
Multiple Sclerosis
Lymphocytes
Transplants
Lymphocyte Subsets
Transplantation Conditioning
T-Lymphocytes
Th17 Cells
Th2 Cells
Th1 Cells
Antilymphocyte Serum
Regulatory T-Lymphocytes
Cyclophosphamide
Disease-Free Survival

Cite this

Cull, Gavin ; Hall, D. ; Fabis-Pedrini, Marzena J. ; Carroll, William MacEwan ; Forster, Luke Benjamin ; Robins, Fiona ; Ghassemifar, Reza ; Crosbie, Christina Tran Cameron ; Walters, Susan Elaine ; James, Ian ; Augustson, Bradley ; Kermode, Allan G. / Lymphocyte reconstitution following autologous stem cell transplantation for progressive MS. In: Multiple Sclerosis Journal - Experimental, Translational and Clinical. 2017 ; Vol. 3, No. 1. pp. 1-9.
@article{5f78553e6f174eddb2c1e4ba0629268a,
title = "Lymphocyte reconstitution following autologous stem cell transplantation for progressive MS",
abstract = "BACKGROUND: Autologous stem cell transplantation (ASCT) for progressive multiple sclerosis (MS) may reset the immune repertoire.OBJECTIVE: The objective of this paper is to analyse lymphocyte recovery in patients with progressive MS treated with ASCT.METHODS: Patients with progressive MS not responding to conventional treatment underwent ASCT following conditioning with high-dose cyclophosphamide and antithymocyte globulin. Lymphocyte subset analysis was performed before ASCT and for two years following ASCT. Neurological function was assessed by the EDSS before ASCT and for three years post-ASCT.RESULTS: CD4+ T-cells fell significantly post-transplant and did not return to baseline levels. Recent thymic emigrants and na{\"i}ve T-cells fell sharply post-transplant but returned to baseline by nine months and twelve months, respectively. T-regulatory cells declined post-transplant and did not return to baseline levels. Th1 and Th2 cells did not change significantly while Th17 cells fell post-transplant but recovered to baseline by six months. Neurological function remained stable in the majority of patients. Progression-free survival was 69{\%} at three years.CONCLUSION: This study demonstrates major changes in the composition of lymphocyte subsets following ASCT for progressive MS. In particular, ablation and subsequent recovery of thymic output is consistent with the concept that ASCT can reset the immune repertoire in MS patients.",
author = "Gavin Cull and D. Hall and Fabis-Pedrini, {Marzena J.} and Carroll, {William MacEwan} and Forster, {Luke Benjamin} and Fiona Robins and Reza Ghassemifar and Crosbie, {Christina Tran Cameron} and Walters, {Susan Elaine} and Ian James and Bradley Augustson and Kermode, {Allan G}",
year = "2017",
month = "6",
day = "14",
doi = "10.1177/2055217317700167",
language = "English",
volume = "3",
pages = "1--9",
journal = "Multiple Sclerosis Journal - Experimental, Translational and Clinical",
issn = "2055-2173",
publisher = "SAGE Publications Ltd",
number = "1",

}

Lymphocyte reconstitution following autologous stem cell transplantation for progressive MS. / Cull, Gavin; Hall, D.; Fabis-Pedrini, Marzena J.; Carroll, William MacEwan; Forster, Luke Benjamin; Robins, Fiona; Ghassemifar, Reza; Crosbie, Christina Tran Cameron; Walters, Susan Elaine; James, Ian; Augustson, Bradley; Kermode, Allan G.

In: Multiple Sclerosis Journal - Experimental, Translational and Clinical, Vol. 3, No. 1, 14.06.2017, p. 1-9.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Lymphocyte reconstitution following autologous stem cell transplantation for progressive MS

AU - Cull, Gavin

AU - Hall, D.

AU - Fabis-Pedrini, Marzena J.

AU - Carroll, William MacEwan

AU - Forster, Luke Benjamin

AU - Robins, Fiona

AU - Ghassemifar, Reza

AU - Crosbie, Christina Tran Cameron

AU - Walters, Susan Elaine

AU - James, Ian

AU - Augustson, Bradley

AU - Kermode, Allan G

PY - 2017/6/14

Y1 - 2017/6/14

N2 - BACKGROUND: Autologous stem cell transplantation (ASCT) for progressive multiple sclerosis (MS) may reset the immune repertoire.OBJECTIVE: The objective of this paper is to analyse lymphocyte recovery in patients with progressive MS treated with ASCT.METHODS: Patients with progressive MS not responding to conventional treatment underwent ASCT following conditioning with high-dose cyclophosphamide and antithymocyte globulin. Lymphocyte subset analysis was performed before ASCT and for two years following ASCT. Neurological function was assessed by the EDSS before ASCT and for three years post-ASCT.RESULTS: CD4+ T-cells fell significantly post-transplant and did not return to baseline levels. Recent thymic emigrants and naïve T-cells fell sharply post-transplant but returned to baseline by nine months and twelve months, respectively. T-regulatory cells declined post-transplant and did not return to baseline levels. Th1 and Th2 cells did not change significantly while Th17 cells fell post-transplant but recovered to baseline by six months. Neurological function remained stable in the majority of patients. Progression-free survival was 69% at three years.CONCLUSION: This study demonstrates major changes in the composition of lymphocyte subsets following ASCT for progressive MS. In particular, ablation and subsequent recovery of thymic output is consistent with the concept that ASCT can reset the immune repertoire in MS patients.

AB - BACKGROUND: Autologous stem cell transplantation (ASCT) for progressive multiple sclerosis (MS) may reset the immune repertoire.OBJECTIVE: The objective of this paper is to analyse lymphocyte recovery in patients with progressive MS treated with ASCT.METHODS: Patients with progressive MS not responding to conventional treatment underwent ASCT following conditioning with high-dose cyclophosphamide and antithymocyte globulin. Lymphocyte subset analysis was performed before ASCT and for two years following ASCT. Neurological function was assessed by the EDSS before ASCT and for three years post-ASCT.RESULTS: CD4+ T-cells fell significantly post-transplant and did not return to baseline levels. Recent thymic emigrants and naïve T-cells fell sharply post-transplant but returned to baseline by nine months and twelve months, respectively. T-regulatory cells declined post-transplant and did not return to baseline levels. Th1 and Th2 cells did not change significantly while Th17 cells fell post-transplant but recovered to baseline by six months. Neurological function remained stable in the majority of patients. Progression-free survival was 69% at three years.CONCLUSION: This study demonstrates major changes in the composition of lymphocyte subsets following ASCT for progressive MS. In particular, ablation and subsequent recovery of thymic output is consistent with the concept that ASCT can reset the immune repertoire in MS patients.

U2 - 10.1177/2055217317700167

DO - 10.1177/2055217317700167

M3 - Article

VL - 3

SP - 1

EP - 9

JO - Multiple Sclerosis Journal - Experimental, Translational and Clinical

JF - Multiple Sclerosis Journal - Experimental, Translational and Clinical

SN - 2055-2173

IS - 1

ER -