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

• DOI: 10.1111/bjh.13917
• Publication Date: 2016-01-05T14:15:06Z
• Authors: Julia Muñoz‐Balle...; Tzu H. Chen‐Liang; Ana M. Hurtado; Inmaculada Heras; Felipe de Arriba; María D. García‐Malo; Pastora Iniesta; María L. Lozano; José B. Nieto; Francisco J. Ortuño; María del M. Osma; José Padilla; Raúl Teruel‐Montoya; Vicente Vicente; Cristina Castilla...; Andrés Jerez
• Keywords: Adult; Male; STAT3 Transcription Factor; Hematopoietic Stem Cell Transplantation; Graft vs Host Disease; Middle Aged; Gene Rearrangement, T-Lymphocyte; Survival Analysis; Immunophenotyping; Neoplasm Proteins; 3. Good health; Leukemia, Large Granular Lymphocytic; Young Adult; 03 medical and health sciences; 0302 clinical medicine; Mutation; Humans; Female; Longitudinal Studies; T-Lymphocytes, Cytotoxic

SummaryPeripheral 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.