title: Persistent cytotoxic T lymphocyte expansions after allogeneic haematopoietic stem cell transplantation: kinetics, clinical impact and absence of STAT3 mutations.
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.
authors.affiliation: Haematology and Medical Oncology Department, University Hospital Morales Meseguer, Centro Regional de Hemodonación, IMIB-Arrixaca, Murcia, Spain.
authors.forename: Julia
authors.initials: J
authors.lastname: Muñoz-Ballester
authors.affiliation: Haematology and Medical Oncology Department, University Hospital Morales Meseguer, Centro Regional de Hemodonación, IMIB-Arrixaca, Murcia, Spain.
authors.forename: Tzu H
authors.initials: TH
authors.lastname: Chen-Liang
authors.affiliation: Haematology and Medical Oncology Department, University Hospital Morales Meseguer, Centro Regional de Hemodonación, IMIB-Arrixaca, Murcia, Spain.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Hurtado
authors.affiliation: Haematology and Medical Oncology Department, University Hospital Morales Meseguer, Centro Regional de Hemodonación, IMIB-Arrixaca, Murcia, Spain.
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Heras
authors.affiliation: Haematology and Medical Oncology Department, University Hospital Morales Meseguer, Centro Regional de Hemodonación, IMIB-Arrixaca, Murcia, Spain.
authors.forename: Felipe
authors.initials: F
authors.lastname: de Arriba
authors.affiliation: Haematology and Medical Oncology Department, University Hospital Morales Meseguer, Centro Regional de Hemodonación, IMIB-Arrixaca, Murcia, Spain.
authors.forename: María D
authors.initials: MD
authors.lastname: García-Malo
authors.affiliation: Haematology and Medical Oncology Department, University Hospital Morales Meseguer, Centro Regional de Hemodonación, IMIB-Arrixaca, Murcia, Spain.
authors.forename: Pastora
authors.initials: P
authors.lastname: Iniesta
authors.affiliation: Haematology and Medical Oncology Department, University Hospital Morales Meseguer, Centro Regional de Hemodonación, IMIB-Arrixaca, Murcia, Spain.
authors.forename: María L
authors.initials: ML
authors.lastname: Lozano
authors.affiliation: Haematology and Medical Oncology Department, University Hospital Morales Meseguer, Centro Regional de Hemodonación, IMIB-Arrixaca, Murcia, Spain.
authors.forename: José B
authors.initials: JB
authors.lastname: Nieto
authors.affiliation: Haematology and Medical Oncology Department, University Hospital Morales Meseguer, Centro Regional de Hemodonación, IMIB-Arrixaca, Murcia, Spain.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Ortuño
authors.affiliation: Haematology and Medical Oncology Department, University Hospital Morales Meseguer, Centro Regional de Hemodonación, IMIB-Arrixaca, Murcia, Spain.
authors.forename: María Del M
authors.initials: Mdel M
authors.lastname: Osma
authors.affiliation: Haematology and Medical Oncology Department, University Hospital Morales Meseguer, Centro Regional de Hemodonación, IMIB-Arrixaca, Murcia, Spain.
authors.forename: José
authors.initials: J
authors.lastname: Padilla
authors.affiliation: Haematology and Medical Oncology Department, University Hospital Morales Meseguer, Centro Regional de Hemodonación, IMIB-Arrixaca, Murcia, Spain.
authors.forename: Raúl
authors.initials: R
authors.lastname: Teruel-Montoya
authors.affiliation: Haematology and Medical Oncology Department, University Hospital Morales Meseguer, Centro Regional de Hemodonación, IMIB-Arrixaca, Murcia, Spain.
authors.forename: Vicente
authors.initials: V
authors.lastname: Vicente
authors.affiliation: Haematology and Medical Oncology Department, University Hospital Morales Meseguer, Centro Regional de Hemodonación, IMIB-Arrixaca, Murcia, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Castilla-Llorente
authors.affiliation: Haematology and Medical Oncology Department, University Hospital Morales Meseguer, Centro Regional de Hemodonación, IMIB-Arrixaca, Murcia, Spain.
authors.forename: Andrés
authors.initials: A
authors.lastname: Jerez
mesh_terms: D000328:Adult; D005260:Female; D015329:Gene Rearrangement, T-Lymphocyte / Q000235:genetics; D006086:Graft vs Host Disease / Q000276:immunology / Q000517:prevention & control; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D016130:Immunophenotyping; D054066:Leukemia, Large Granular Lymphocytic / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics; D050796:STAT3 Transcription Factor / Q000235:genetics*; D016019:Survival Analysis; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D055815:Young Adult
chemical_list: D009363:Neoplasm Proteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human
keywords: T cell receptor rearrangement; allogeneic haematopoietic stem cell transplantation; large granular lymphocyte; lymphocytes; signal transducer and activator of transcription 3