Detailed immunophenotyping of the hematopoietic graft from patients with multiple sclerosis undergoing autologous hematopoietic stem cell transplant

Jennifer Massey; Malini Visweswaran; Melissa Khoo; Kevin Hendrawan; Ian Sutton; Barbara Withers; David Ma; John Moore

doi:10.1016/j.jcyt.2023.08.010

Detailed immunophenotyping of the hematopoietic graft from patients with multiple sclerosis undergoing autologous hematopoietic stem cell transplant

Cytotherapy. 2023 Dec;25(12):1271-1276. doi: 10.1016/j.jcyt.2023.08.010. Epub 2023 Sep 21.

Authors

Jennifer Massey¹, Malini Visweswaran², Melissa Khoo², Kevin Hendrawan³, Ian Sutton⁴, Barbara Withers⁵, David Ma⁵, John Moore⁵

Affiliations

¹ Department of Haematology, St. Vincent's Hospital, Darlinghurst, Australia; Department of Neurology, St. Vincent's Hospital, Darlinghurst, Australia; Blood Stem Cell and Cancer Research Group, St. Vincent's Centre for Applied Medical Research, Darlinghurst, Australia; UNSW School of Clinical Medicine, University of New South Wales, Kensington, Australia. Electronic address: jennifer.massey@svha.org.au.
² Blood Stem Cell and Cancer Research Group, St. Vincent's Centre for Applied Medical Research, Darlinghurst, Australia.
³ Drug Discovery Group, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
⁴ UNSW School of Clinical Medicine, University of New South Wales, Kensington, Australia.
⁵ Department of Haematology, St. Vincent's Hospital, Darlinghurst, Australia; Blood Stem Cell and Cancer Research Group, St. Vincent's Centre for Applied Medical Research, Darlinghurst, Australia; UNSW School of Clinical Medicine, University of New South Wales, Kensington, Australia.

PMID: 37737765
DOI: 10.1016/j.jcyt.2023.08.010

Abstract

Background aims: Autologous hematopoietic stem cell transplantation (AHSCT) is a highly effective therapy for relapsing multiple sclerosis. Re-infused stem cells provide "rescue" from the pancytopenia induced by immuno-chemotherapy. To date, no study has analyzed the non-stem cell content of the leukapheresis product (graft) in regards to its influence on disease remission in AHSCT for multiple sclerosis (MS).

Methods: Detailed immunophenotyping of the stem cell graft was performed in a cohort of highly active patients with MS (n = 22) followed for a median of 6 years' post-AHSCT.

Results: Effector memory populations thought to house pathogenic clones including Th17 cells and central nervous system homing T cells were detected in the graft at similar proportions to pre-AHSCT. There was no association between absolute counts of these populations in the graft and treatment response. Only in responder patients was there evidence of a significant decrease in these putative pro-inflammatory populations by 3 months' post-transplant. Although there was no statistical difference in the number of T regulatory cells (Tregs) in the graft between responders and relapsing patients, the absolute count of Tregs in the graft correlated with circulating Tregs in the first 6 months post-AHSCT in responders alone.

Conclusions: Our results collectively suggest that the early establishment of immune tolerance post-AHSCT appears to relate to a decrease in putative pathogenic cell populations following reinfusion, and that Treg load in the leukapheresis product is less relevant to treatment response than the early expansion of graft-derived Tregs. It therefore remains unclear whether employment of CD34 selection to manipulate the graft may offer additional benefit in remission rates post-AHSCT for MS. Cellular therapy targeted toward early Treg expansion may provide recourse for long-term remission rates in MS.

Keywords: T regulatory cells; immune reconstitution; leukapheresis product; multiple sclerosis; stem cell transplantation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Hematopoietic Stem Cell Transplantation*
Humans
Immunophenotyping
Multiple Sclerosis* / therapy
Stem Cell Transplantation
Transplantation, Autologous