en
Scientific article
Open access
English

Genetic T-cell receptor diversity at 1 year following allogeneic hematopoietic stem cell transplantation

Published inLeukemia, vol. 34, no. 5, p. 1422-1432
Publication date2020
Abstract

After allogeneic hematopoietic stem cell transplantation (HSCT), immune reconstitution leads to the development of a new T-cell repertoire. Immune reconstitution could be influenced by events such as conditioning, infections, and graft versus host disease (GVHD). Factors influencing the TCR diversity are of great interest to fine-tune the strategy for donor selection and to optimize standard of care. In this work, immunosequencing of the TCR CDR3β region was carried out in a large cohort of 116 full chimeric recipients at 1 year post-HSCT and their respective donors prior to transplantation. The repertoire overlap before and after HSCT was minimal, supporting de novo reconstitution as a primary pathway at any age. Among the parameters investigated, increased patient and/or donor age as well as positive CMV serologic status reinforced by CMV infection/reactivation were the ones significantly associated with a reduced diversity at 1 year post-HSCT. CMV-specific T-cell clones were shown to influence the clonality of the repertoire alongside the expansion of limited numbers of non-CMV T-cell populations. Interestingly, at the exception of CMV infection/reactivation, TCR diversity was not predictive of GVHD, relapse, death, or infections post-HSCT.

Keywords
  • Adolescent
  • Adult
  • Aged
  • Child
  • Child, Preschool
  • Cohort Studies
  • Cytomegalovirus/isolation & purification
  • Cytomegalovirus Infections/diagnosis/etiology/genetics
  • Female
  • Follow-Up Studies
  • Graft vs Host Disease/diagnosis/etiology/genetics
  • Hematologic Neoplasms/pathology/therapy
  • Hematopoietic Stem Cell Transplantation/adverse effects
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Middle Aged
  • Mutation
  • Prognosis
  • Receptors, Antigen, T-Cell/genetics
  • Tissue Donors/supply & distribution
  • Transplantation Conditioning
  • Transplantation, Homologous
  • Virus Activation
  • Young Adult
Citation (ISO format)
BUHLER, Stéphane et al. Genetic T-cell receptor diversity at 1 year following allogeneic hematopoietic stem cell transplantation. In: Leukemia, 2020, vol. 34, n° 5, p. 1422–1432. doi: 10.1038/s41375-019-0654-y
Main files (2)
Article (Published version)
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Article (Accepted version)
accessLevelPublic
Secondary files (1)
Identifiers
ISSN of the journal0887-6924
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190downloads

Technical informations

Creation10/21/2020 1:49:00 PM
First validation10/21/2020 1:49:00 PM
Update time03/15/2023 10:55:10 PM
Status update03/15/2023 10:55:08 PM
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