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Persistent cytotoxic T lymphocyte expansions after allogeneic haematopoietic stem cell transplantation: kinetics, clinical impact and absence of STAT 3 mutations
Author(s) -
MuñozBallester Julia,
ChenLiang Tzu H.,
Hurtado Ana M.,
Heras Inmaculada,
Arriba Felipe,
GarcíaMalo María D.,
Iniesta Pastora,
Lozano María L.,
Nieto José B.,
Ortuño Francisco J.,
Osma María del M.,
Padilla José,
TeruelMontoya Raúl,
Vicente Vicente,
CastillaLlorente Cristina,
Jerez Andrés
Publication year - 2016
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.13917
Subject(s) - transplantation , ctl* , immunology , thymoglobulin , cytotoxic t cell , haematopoiesis , biology , stem cell , immune system , hematopoietic stem cell transplantation , lymphocyte , cd8 , medicine , kidney transplantation , genetics , in vitro
Summary Peripheral expansion of cytotoxic T lymphocytes ( CTL ) derived from the graft in the initial stages of allogeneic haematopoietic stem cell transplantation (allo HSCT ) 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 ( CTL e) persists beyond the early transplantation period. We aimed to assess the nature of CTL e during the post‐allo HSCT 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‐ STAT 3 mutations. Persistent relative CTL e 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 CTL e are scarce (9%) and related to chronic GVHD . T cell receptor rearrangement was reported as clonal and oligoclonal in the majority of patients with CTL e. The absence of STAT 3 mutations and the CD 8/ CD 4 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.