Persistent cytotoxic T lymphocyte expansions after allogeneic haematopoietic stem cell transplantation: kinetics, clinical impact and absence of STAT3 mutations

Br J Haematol. 2016 Mar;172(6):937-46. doi: 10.1111/bjh.13917. Epub 2016 Jan 5.

Abstract

Peripheral expansion of cytotoxic T lymphocytes (CTL) derived from the graft in the initial stages of allogeneic haematopoietic stem cell transplantation (alloHSCT) immune recovery is a well-known physiological event. The description of symptomatic large granular lymphocyte leukaemia in this setting may generate uncertainty, mostly in those cases in which the CTL expansion (CTLe) persists beyond the early transplantation period. We aimed to assess the nature of CTLe during the post-alloHSCT period in 154 adult patients with a long-term surveillance. We studied the longitudinal kinetics of those expansions, their relationship to clinical events, and their phenotypic and molecular features, including recently reported CTL leukaemia-STAT3 mutations. Persistent relative CTLe cases are frequent (49%), related with thymoglobulin prophylaxis (P ≤ 0·001), acute graft-versus-host disease (GVHD, P = 0·02), and reduced intensity conditioning (P = 0·04). Absolute CTLe are scarce (9%) and related to chronic GVHD. T cell receptor rearrangement was reported as clonal and oligoclonal in the majority of patients with CTLe. The absence of STAT3 mutations and the CD8/CD4 declining longitudinal kinetics in the late period supports its benign nature, expressed clinically by the null detrimental impact of these expansions on post-transplant outcome and/or serious infectious events.

Keywords: T cell receptor rearrangement; allogeneic haematopoietic stem cell transplantation; large granular lymphocyte; lymphocytes; signal transducer and activator of transcription 3.

MeSH terms

  • Adult
  • Female
  • Gene Rearrangement, T-Lymphocyte / genetics
  • Graft vs Host Disease / immunology
  • Graft vs Host Disease / prevention & control
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Immunophenotyping
  • Leukemia, Large Granular Lymphocytic / genetics
  • Leukemia, Large Granular Lymphocytic / immunology
  • Leukemia, Large Granular Lymphocytic / therapy*
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Mutation*
  • Neoplasm Proteins / genetics
  • STAT3 Transcription Factor / genetics*
  • Survival Analysis
  • T-Lymphocytes, Cytotoxic / immunology*
  • Young Adult

Substances

  • Neoplasm Proteins
  • STAT3 Transcription Factor
  • STAT3 protein, human