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Pharmacodynamics of T cell function for monitoring pharmacologic immunosuppression after allogeneic hematopoietic stem cell transplantation

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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.

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Acknowledgements

This study was supported by the Instituto de Salud Carlos III (Grant PS09/01043), Subdirección General de Evaluación y Fomento de la Investigación, Ministerio de Economía y Competitividad, España. CIBERehd is funded by the Instituto de Salud Carlos III. The authors thank nurse and technicians teams from Stem Cell Transplantation Unit of Hematology Department and Pharmacology and Toxicology Department, for their excellent assistance.

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Authors and Affiliations

  1. Hematology Department, Institute of Hematology and Oncology, Hospital Clínic, University of Barcelona, Villarroel 170, 08039, Barcelona, Spain

    Carmen Martínez, Montserrat Rovira, Francesc Fernández-Avilés, María Suárez-Lledó & Álvaro Urbano-Ispízua

  2. Institut Josep Carreras, Hospital Clínic, University of Barcelona, Barcelona, Spain

    Carmen Martínez, Montserrat Rovira, Francesc Fernández-Avilés, Enric Carreras & Álvaro Urbano-Ispízua

  3. Pharmacology and Toxicology Department, Biomedical Diagnostic Center, Hospital Clínic, University of Barcelona, Barcelona, Spain

    Olga Millán, Anna López & Mercè Brunet

  4. CIBERehd, Hospital Clínic, University of Barcelona, Barcelona, Spain

    Olga Millán & Mercè Brunet

  5. Institut d’Investigació Biomèdica Agustí Pi I Sunyer (IDIBAPS), Hospital Clínic, University of Barcelona, Barcelona, Spain

    Carmen Martínez, Olga Millán, Montserrat Rovira, Francesc Fernández-Avilés, Anna López, Álvaro Urbano-Ispízua & Mercè Brunet

  6. Hospital Clínic, University of Barcelona, Barcelona, Spain

    Carmen Martínez, Olga Millán, Montserrat Rovira, Francesc Fernández-Avilés, Álvaro Urbano-Ispízua & Mercè Brunet

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  1. Carmen Martínez
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  2. Olga Millán
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Correspondence to Carmen Martínez.

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Martínez, C., Millán, O., Rovira, M. et al. Pharmacodynamics of T cell function for monitoring pharmacologic immunosuppression after allogeneic hematopoietic stem cell transplantation. Int J Hematol 105, 497–505 (2017). https://doi.org/10.1007/s12185-016-2145-5

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  • DOI: https://doi.org/10.1007/s12185-016-2145-5

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