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The Dogma

Cytomegalovirus promotes expansion of pre-existing T-cell immunity following allogeneic transplantation significantly modulating chimerism status.

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The Dogma

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  1. Cytomegalovirus promotes expansion of pre-existing T-cell immunity following allogeneic transplantation significantly modulating chimerism status Rob S. Sellar, Frederick Arce Vargas, Jake Y. Henry, Stephanie Verfuerth, Sarah Charrot, Sergio A. Quezada, Stephen Mackinnon, Kirsty J. Thomson, and Karl S. Peggs* University College London Cancer Institute

  2. The Dogma • CMV reactivations are increased if you T-deplete • Highest risk population R+/D- • New therapeutic strategies are needed

  3. What if it is wrong?

  4. What if it is wrong? CMV reactivations

  5. What if it is wrong? CMV reactivations Days of treatment

  6. Problematic CMV reactivations are associated with low levels of recipient chimerism CMV reactivations

  7. Problematic CMV reactivations are associated with low levels of recipient chimerism CMV reactivations Days of treatment

  8. Problematic CMV reactivations are restricted to patients with significant GvHD CMV reactivations

  9. Problematic CMV reactivations are restricted to patients with significant GvHD Days of treatment CMV reactivations

  10. Patients with significant GvHD had lower absolute lymphocyte counts

  11. CMV appears to influence levels of recipient chimerism

  12. CMV appears to influence levels of recipient chimerism

  13. CMV appears to influence levels of recipient chimerism

  14. CMV influences chimerism even in the absence of GvHD

  15. Streptamer positive cells are exclusively of recipient origin

  16. Streptamer positive cells are exclusively of recipient origin Donor Recipient CD4+ CD8+ Strep- CD8+ Strep+ Patient 1 Patient 2 Patient 3

  17. DLI can be followed by a primary immune response to CMV Donor Recipient CD8+ Strep- CD8+ Strep+ CD4+ Pre-DLI 4 weeks 8 weeks 12 weeks 18 weeks

  18. Conclusions • recipient-derived virus-specific T cells that have escaped deletion during non-myeloablative conditioning can protect against recurrent CMV infection • expansion of these cells post transplant has a significant influence on levels of recipient chimerism • “Campath Paradox” - T cell-depletion in the R+D- setting may paradoxically foster more rapid reconstitution of protective antiviral immunity by reducing graft-versus-host directed alloreactivity and the associated elimination of the recipient T cell compartment

  19. Acknowledgements • UCL Cancer Institute • Tumour Immunogy Group – Dr Karl S Peggs – Dr Sergio A Quesada – Dr Frederick Arce Vargas – Jake Y Henry • Royal Free Hospital – Professor Stephen Mackinnon – Stephanie Verfuerth • UCLH – Dr Kirsty Thomson – Dr Sarah Charrot

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