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Post-Transplant Events

Polyomavirus JC-targeted T-cell therapy for progressive multiple leukoencephalopathy in a hematopoietic cell transplantation recipient

Bone Marrow Transplantation volume 46, pages 987–992 (2011)Cite this article

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Abstract

Progressive multifocal leukoencephalopathy (PML) associated with polyomavirus JC (JCV) infection has been reported to be usually fatal in allogeneic hematopoietic SCT (HSCT) recipients. We present the case of a 19-year-old HSCT patient diagnosed with JCV-associated PML after prolonged immunosuppression for severe GVHD. No short-term neurological improvement was observed after antiviral treatment and discontinuation of immunosuppressive therapy. Donor-derived JCV Ag-specific CTLs were generated in vitro after stimulation with 15-mer peptides derived from VP1 and large T viral proteins. After adoptive CTL infusion, virus-specific cytotoxic cells were shown in the peripheral blood, JCV-DNA was cleared in the cerebrospinal fluid and the patient showed remarkable improvement. Adoptive T-lymphocyte therapy with JCV-specific CTLs was feasible and had no side effects. This case suggests that adoptive transfer of JCV-targeted CTLs may contribute to restore JCV-specific immune competence and control PML in transplanted patients.

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Acknowledgements

This work has been partly supported by grants from AIRC (Associazione Italiana Ricerca sul Cancro) to PC, EB, FL and AB; Regione Lombardia to FL and AB; MIUR (Ministero dell'Istruzione, dell'Università e della Ricerca) to EB, FL and AB; Ministero della Salute, Progetti Ricerca Oncologica number RFPS-2006-4-341763 to FL; number RFPS-2006-2-340145 to FL; number RFPS-2006-Regione Umbria to PC and FL; Fondazione Cariplo to AB; and Fondazione IRCCS (Istituto di Ricovero e Cura a Carattere Scientifico) Policlinico San Matteo to FL. We thank the Comitato Maria Letizia Verga, Fondazione Matilde Tettamanti and Comitato Stefano Verri for their continuous support and Mrs Joanna Upton for linguistic assistance. Dr Cioni is the recipient of a scholarship from Fondazione Malattie Renali del Bambino, Genova, Italy.

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Authors and Affiliations

  1. Clinica Pediatrica Università degli Studi di Milano Bicocca, Ospedale San Gerardo, Monza, Italy

    A Balduzzi, G Lucchini, A Rovelli, P Corti, S Bonanomi, A Biondi & E Biagi

  2. Department of Molecular Diagnostics, Clinical and Transplantation Virology, Institute for Medical Microbiology, University of Basel, Basel, Switzerland

    H H Hirsch

  3. Department of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Basel, Switzerland

    H H Hirsch

  4. Dipartimento Materno-Infantile, Pediatric Hematology/Oncology, Fondazione IRCCS Policlinico S Matteo, University of Pavia, Pavia, Italy

    S Basso, M Cioni & P Comoli

  5. Clinica Neurologica Università degli Studi di Milano Bicocca, Ospedale San Gerardo, Monza, Italy

    A Zincone

  6. Department of Radiology, Ospedale San Gerardo, Monza, Italy

    M Grimaldi

  7. Dipartimento di Oncoematologia Pediatrica IRCCS Ospedale Pediatrico Bambino Gesú, Roma, Italy

    F Locatelli

  8. Universitá degli Studi de Pavia, Pavia, Italy

    F Locatelli

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  1. A Balduzzi
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  2. G Lucchini
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  3. H H Hirsch
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Correspondence to A Balduzzi.

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Balduzzi, A., Lucchini, G., Hirsch, H. et al. Polyomavirus JC-targeted T-cell therapy for progressive multiple leukoencephalopathy in a hematopoietic cell transplantation recipient. Bone Marrow Transplant 46, 987–992 (2011). https://doi.org/10.1038/bmt.2010.221

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