title: Pharmacodynamics of T cell function for monitoring pharmacologic immunosuppression after allogeneic hematopoietic stem cell transplantation.
abstract: Information on pharmacodynamic monitoring after allogeneic hematopoietic cell transplantation (allo-SCT) to evaluate individual responses to immunosuppressive drugs is scarce. We studied the relationship between a panel of pharmacodynamic markers monitored during the first 3 months after transplant and the occurrence of graft-versus-host disease (GVHD). Lymphocyte activation assessed by intracellular ATP concentration in CD4+T cells, a high percentage of CD8+effector T cells, and a low percentage of CD4+regulatory T (Treg) cells correlated significantly with GVHD. A cutoff value of 0.5 for the CD8+effector T/Treg ratio provided the most accurate diagnosis of GVHD (sensitivity 58.8%, specificity 91%). These pharmacodynamic markers may provide an efficient complement to standard pharmacokinetic monitoring of immunosuppressive drugs after allo-SCT.
authors.affiliation: Hematology Department, Institute of Hematology and Oncology, Hospital Clínic, University of Barcelona, Villarroel 170, 08039, Barcelona, Spain. cmarti@clinic.ub.es.|Institut Josep Carreras, Hospital Clínic, University of Barcelona, Barcelona, Spain. cmarti@clinic.ub.es.|Institut d'Investigació Biomèdica Agustí Pi I Sunyer (IDIBAPS), Hospital Clínic, University of Barcelona, Barcelona, Spain. cmarti@clinic.ub.es.|Hospital Clínic, University of Barcelona, Barcelona, Spain. cmarti@clinic.ub.es.
authors.forename: Carmen
authors.initials: C
authors.lastname: Martínez
authors.affiliation: Pharmacology and Toxicology Department, Biomedical Diagnostic Center, Hospital Clínic, University of Barcelona, Barcelona, Spain.|CIBERehd, Hospital Clínic, University of Barcelona, Barcelona, Spain.|Institut d'Investigació Biomèdica Agustí Pi I Sunyer (IDIBAPS), Hospital Clínic, University of Barcelona, Barcelona, Spain.|Hospital Clínic, University of Barcelona, Barcelona, Spain.
authors.forename: Olga
authors.initials: O
authors.lastname: Millán
authors.affiliation: Hematology Department, Institute of Hematology and Oncology, Hospital Clínic, University of Barcelona, Villarroel 170, 08039, Barcelona, Spain.|Institut Josep Carreras, Hospital Clínic, University of Barcelona, Barcelona, Spain.|Institut d'Investigació Biomèdica Agustí Pi I Sunyer (IDIBAPS), Hospital Clínic, University of Barcelona, Barcelona, Spain.|Hospital Clínic, University of Barcelona, Barcelona, Spain.
authors.forename: Montserrat
authors.initials: M
authors.lastname: Rovira
authors.affiliation: Hematology Department, Institute of Hematology and Oncology, Hospital Clínic, University of Barcelona, Villarroel 170, 08039, Barcelona, Spain.|Institut Josep Carreras, Hospital Clínic, University of Barcelona, Barcelona, Spain.|Institut d'Investigació Biomèdica Agustí Pi I Sunyer (IDIBAPS), Hospital Clínic, University of Barcelona, Barcelona, Spain.|Hospital Clínic, University of Barcelona, Barcelona, Spain.
authors.forename: Francesc
authors.initials: F
authors.lastname: Fernández-Avilés
authors.affiliation: Pharmacology and Toxicology Department, Biomedical Diagnostic Center, Hospital Clínic, University of Barcelona, Barcelona, Spain.|Institut d'Investigació Biomèdica Agustí Pi I Sunyer (IDIBAPS), Hospital Clínic, University of Barcelona, Barcelona, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: López
authors.affiliation: Hematology Department, Institute of Hematology and Oncology, Hospital Clínic, University of Barcelona, Villarroel 170, 08039, Barcelona, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Suárez-Lledó
authors.affiliation: Institut Josep Carreras, Hospital Clínic, University of Barcelona, Barcelona, Spain.
authors.forename: Enric
authors.initials: E
authors.lastname: Carreras
authors.affiliation: Hematology Department, Institute of Hematology and Oncology, Hospital Clínic, University of Barcelona, Villarroel 170, 08039, Barcelona, Spain.|Institut Josep Carreras, Hospital Clínic, University of Barcelona, Barcelona, Spain.|Institut d'Investigació Biomèdica Agustí Pi I Sunyer (IDIBAPS), Hospital Clínic, University of Barcelona, Barcelona, Spain.|Hospital Clínic, University of Barcelona, Barcelona, Spain.
authors.forename: Álvaro
authors.initials: Á
authors.lastname: Urbano-Ispízua
authors.affiliation: Pharmacology and Toxicology Department, Biomedical Diagnostic Center, Hospital Clínic, University of Barcelona, Barcelona, Spain.|CIBERehd, Hospital Clínic, University of Barcelona, Barcelona, Spain.|Institut d'Investigació Biomèdica Agustí Pi I Sunyer (IDIBAPS), Hospital Clínic, University of Barcelona, Barcelona, Spain.|Hospital Clínic, University of Barcelona, Barcelona, Spain.
authors.forename: Mercè
authors.initials: M
authors.lastname: Brunet
mesh_terms: D000328:Adult; D000368:Aged; D064591:Allografts; D015415:Biomarkers / Q000097:blood; D016516:CD4-CD8 Ratio; D016903:Drug Monitoring / Q000379:methods; D005260:Female; D006086:Graft vs Host Disease / Q000175:diagnosis*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods*; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D015415:Biomarkers; D007166:Immunosuppressive Agents
keywords: Allogeneic stem cell transplantation; Graft-versus-host disease; Pharmacodynamics; T effector cells; Treg cells