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Cytomegalovirus promotes expansion of preexisting 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
The Dogma
• CMV reactivations are increased if you T-deplete
• Highest risk population R+/D• New therapeutic strategies are needed
What if it is wrong?
What if it is wrong?
CMV reactivations
What if it is wrong?
CMV reactivations
Days of treatment
Problematic CMV reactivations are
associated with low levels of recipient
chimerism
CMV reactivations
Problematic CMV reactivations are
associated with low levels of recipient
chimerism
CMV reactivations
Days of treatment
Problematic CMV reactivations are restricted
to patients with significant GvHD
CMV reactivations
p < 0.0001
Number of CMV reactivations
15
10
5
0
Significant GvHD
Nonsignificant/No GvHD
Problematic CMV reactivations are restricted
to patients with significant GvHD
Days of treatment
CMV reactivations
p < 0.0001
Number of days of treatment for CMV
Number of CMV reactivations
15
p = 0.0003
10
5
0
Significant GvHD
Nonsignificant/No GvHD
500
400
300
200
100
0
Significant GvHD
Nonsignificant/No GvHD
Patients with significant GvHD had lower
absolute lymphocyte counts
CMV appears to influence levels of recipient
chimerism
CMV appears to influence levels of recipient
chimerism
CMV appears to influence levels of recipient
chimerism
CMV influences chimerism even in the
absence of GvHD
Streptamer positive cells are exclusively of recipient origin
Streptamer positive cells are exclusively of recipient origin
Donor
Recipient
CD4+
CD8+ Strep-
CD8+ Strep+
Patient 1
Patient 2
Patient 3
DLI can be followed by a primary immune
response to CMV
Donor
Recipient
CD8+ Strep-
Pre-DLI
4 weeks
8 weeks
12 weeks
18 weeks
CD8+ Strep+
CD4+
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
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