Progressive multifocal leukoencephalopathy in a patient post allo-HCT successfully treated with JC virus specific donor lymphocytes
Abstract Background Progressive multifocal leukoencephalopathy is a demyelinating CNS disorder. Reactivation of John Cunningham virus leads to oligodendrocyte infection with lysis and consequent axonal loss due to demyelination. Patients usually present with confusion and seizures. Late diagnosis an...
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| Format: | Article |
| Language: | English |
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BMC
2020-04-01
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| Series: | Journal of Translational Medicine |
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| Online Access: | http://link.springer.com/article/10.1186/s12967-020-02337-5 |
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| author | M. J. Steinhardt E. Wiercinska M. Pham G. U. Grigoleit A. Mazzoni M. Da-Via X. Zhou K. Meckel K. Nickel J. Duell F. C. Krummenast S. Kraus C. Hopkinson B. Weissbrich W. Müllges G. Stoll K. M. Kortüm H. Einsele H. Bonig L. Rasche |
| author_facet | M. J. Steinhardt E. Wiercinska M. Pham G. U. Grigoleit A. Mazzoni M. Da-Via X. Zhou K. Meckel K. Nickel J. Duell F. C. Krummenast S. Kraus C. Hopkinson B. Weissbrich W. Müllges G. Stoll K. M. Kortüm H. Einsele H. Bonig L. Rasche |
| author_sort | M. J. Steinhardt |
| collection | DOAJ |
| description | Abstract Background Progressive multifocal leukoencephalopathy is a demyelinating CNS disorder. Reactivation of John Cunningham virus leads to oligodendrocyte infection with lysis and consequent axonal loss due to demyelination. Patients usually present with confusion and seizures. Late diagnosis and lack of adequate therapy options persistently result in permanent impairment of brain functions. Due to profound T cell depletion, impairment of T-cell function and potent immunosuppressive factors, allogeneic hematopoietic cell transplantation recipients are at high risk for JCV reactivation. To date, PML is almost universally fatal when occurring after allo-HCT. Methods To optimize therapy specificity, we enriched JCV specific T-cells out of the donor T-cell repertoire from the HLA-identical, anti-JCV-antibody positive family stem cell donor by unstimulated peripheral apheresis [1]. For this, we selected T cells responsive to five JCV peptide libraries via the Cytokine Capture System technology. It enables the enrichment of JCV specific T cells via identification of stimulus-induced interferon gamma secretion. Results Despite low frequencies of responsive T cells, we succeeded in generating a product containing 20 000 JCV reactive T cells ready for patient infusion. The adoptive cell transfer was performed without complication. Consequently, the clinical course stabilized and the patient slowly went into remission of PML with JCV negative CSF and containment of PML lesion expansion. Conclusion We report for the first time feasibility of generating T cells with possible anti-JCV activity from a seropositive family donor, a variation of virus specific T-cell therapies suitable for the post allo transplant setting. We also present the unusual case for successful treatment of PML after allo-HCT via virus specific T-cell therapy. |
| first_indexed | 2024-12-10T21:49:42Z |
| format | Article |
| id | doaj.art-10cda74355634387a07459a8bcf86dfe |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-12-10T21:49:42Z |
| publishDate | 2020-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-10cda74355634387a07459a8bcf86dfe2022-12-22T01:32:14ZengBMCJournal of Translational Medicine1479-58762020-04-011811610.1186/s12967-020-02337-5Progressive multifocal leukoencephalopathy in a patient post allo-HCT successfully treated with JC virus specific donor lymphocytesM. J. Steinhardt0E. Wiercinska1M. Pham2G. U. Grigoleit3A. Mazzoni4M. Da-Via5X. Zhou6K. Meckel7K. Nickel8J. Duell9F. C. Krummenast10S. Kraus11C. Hopkinson12B. Weissbrich13W. Müllges14G. Stoll15K. M. Kortüm16H. Einsele17H. Bonig18L. Rasche19Department of Internal Medicine II, University Hospital WürzburgDepartment of Cellular Therapeutics (GMP), German Red Cross Blood Service BaWüHe, Institute FrankfurtInstitute of Diagnostic and Interventional Neuroradiology, University Hospital of WürzburgDepartment of Internal Medicine II, University Hospital WürzburgImmunohematology Unit, Azienda Ospedaliera Universitaria PisanaDepartment of Internal Medicine II, University Hospital WürzburgDepartment of Internal Medicine II, University Hospital WürzburgDepartment of Internal Medicine II, University Hospital WürzburgDepartment of Internal Medicine II, University Hospital WürzburgDepartment of Internal Medicine II, University Hospital WürzburgDepartment of Internal Medicine II, University Hospital WürzburgDepartment of Internal Medicine II, University Hospital WürzburgNortheastern Oklahoma Community Health CenterInstitute of Virology and Immunobiology, University of WürzburgDepartment of Neurology, University Hospital WürzburgDepartment of Neurology, University Hospital WürzburgDepartment of Internal Medicine II, University Hospital WürzburgDepartment of Internal Medicine II, University Hospital WürzburgInstitute for Transfusion Medicine and Immunohematology, Goethe UniversityDepartment of Internal Medicine II, University Hospital WürzburgAbstract Background Progressive multifocal leukoencephalopathy is a demyelinating CNS disorder. Reactivation of John Cunningham virus leads to oligodendrocyte infection with lysis and consequent axonal loss due to demyelination. Patients usually present with confusion and seizures. Late diagnosis and lack of adequate therapy options persistently result in permanent impairment of brain functions. Due to profound T cell depletion, impairment of T-cell function and potent immunosuppressive factors, allogeneic hematopoietic cell transplantation recipients are at high risk for JCV reactivation. To date, PML is almost universally fatal when occurring after allo-HCT. Methods To optimize therapy specificity, we enriched JCV specific T-cells out of the donor T-cell repertoire from the HLA-identical, anti-JCV-antibody positive family stem cell donor by unstimulated peripheral apheresis [1]. For this, we selected T cells responsive to five JCV peptide libraries via the Cytokine Capture System technology. It enables the enrichment of JCV specific T cells via identification of stimulus-induced interferon gamma secretion. Results Despite low frequencies of responsive T cells, we succeeded in generating a product containing 20 000 JCV reactive T cells ready for patient infusion. The adoptive cell transfer was performed without complication. Consequently, the clinical course stabilized and the patient slowly went into remission of PML with JCV negative CSF and containment of PML lesion expansion. Conclusion We report for the first time feasibility of generating T cells with possible anti-JCV activity from a seropositive family donor, a variation of virus specific T-cell therapies suitable for the post allo transplant setting. We also present the unusual case for successful treatment of PML after allo-HCT via virus specific T-cell therapy.http://link.springer.com/article/10.1186/s12967-020-02337-5MyelomaJCVProdigyCCSPMLDonor lymphocytes |
| spellingShingle | M. J. Steinhardt E. Wiercinska M. Pham G. U. Grigoleit A. Mazzoni M. Da-Via X. Zhou K. Meckel K. Nickel J. Duell F. C. Krummenast S. Kraus C. Hopkinson B. Weissbrich W. Müllges G. Stoll K. M. Kortüm H. Einsele H. Bonig L. Rasche Progressive multifocal leukoencephalopathy in a patient post allo-HCT successfully treated with JC virus specific donor lymphocytes Journal of Translational Medicine Myeloma JCV Prodigy CCS PML Donor lymphocytes |
| title | Progressive multifocal leukoencephalopathy in a patient post allo-HCT successfully treated with JC virus specific donor lymphocytes |
| title_full | Progressive multifocal leukoencephalopathy in a patient post allo-HCT successfully treated with JC virus specific donor lymphocytes |
| title_fullStr | Progressive multifocal leukoencephalopathy in a patient post allo-HCT successfully treated with JC virus specific donor lymphocytes |
| title_full_unstemmed | Progressive multifocal leukoencephalopathy in a patient post allo-HCT successfully treated with JC virus specific donor lymphocytes |
| title_short | Progressive multifocal leukoencephalopathy in a patient post allo-HCT successfully treated with JC virus specific donor lymphocytes |
| title_sort | progressive multifocal leukoencephalopathy in a patient post allo hct successfully treated with jc virus specific donor lymphocytes |
| topic | Myeloma JCV Prodigy CCS PML Donor lymphocytes |
| url | http://link.springer.com/article/10.1186/s12967-020-02337-5 |
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