Abstract
Background aims. Identifying patients who spontaneously resolve cytomegalovirus (CMV) reactivation could spare these patients from the toxicity of antiviral drugs such as ganciclovir. The role of CMV-specific T cells in clearing CMV viremia in patients who do not receive ganciclovir has not been evaluated. We assessed this in patients with CMV viremia between 50 and 50 000 genome copies/mL, because our threshold for initiating ganciclovir is 50 000 copies/mL. Methods. We enumerated CMV-specific T cells in 39 CMV seropositive hematopoietic cell transplantation (HCT) recipients within 4 days of the first positive CMV polymerase chain reaction (PCR). CMV-specific T cells were defined as cells that upon stimulation with CMV lysate or pp65 overlapping peptides produced interferon (IFN)-γ, tumor necrosis factor (TNF)-α or interleukin (IL)-2, alone or in combination. Results. Among Donor (D+), Recipient (R+) patients, unifunctional CMV-specific CD4 T-cells were higher in patients who spontaneously resolved CMV viremia (did not receive ganciclovir) versus those who progressed (received ganciclovir) (median 0.20 versus 0.02/μL lysate-stimulated cells, P < 0.05, and 0.26 versus 0.05/μL pp65 peptide-stimulated cells, P<0.05). Among D− R+ patients, there was no difference between patients with spontaneous resolution or progression; all subsets of CMV-specific T cells measured were barely detectable, in both patients with spontaneous resolution and those with progression. Conclusions. Among D+ R+ patients (but not D− R+ patients), high CMV-specific CD4 T-cell counts identify patients who can spontaneously resolve CMV reactivation. In D− R+ patients, immune mechanisms other than T cells may control the progression from reactivation to high-level viremia/disease.
Acknowledgements
We thank the patients for participating in research that could not benefit them but only future patients. This study could not happen without the dedication of the staff of Alberta Provincial Lab, especially Dr Julie Fox, Dr Raymond Tellier, Vinod Khurana, the staff of Calgary Lab Services, especially Glennis Doiron, and the staff of the Alberta Blood and Marrow Transplant Program, especially Polly Louie Lynne Fisk, Judy Wu, Diana Quinlan, Jan McLaughlin, Maggie Young, as well as all in-patient nurses (headed by Lorraine Harrison, Joanne Leavitt and Jody Seerup), out-patient nurses (headed by Marie-Josee Paquin and Naree Ager) and physicians including Drs Ahsan Chaudhry, Nancy Zacarias, Ping Yue, Nizar Bahlis, Chris Brown, Andrew Daly, Peter Duggan, Michelle Geddes, Lynn Savoie Douglas Stewart, Mona Shafey, Melaku Game, Loree Larratt and Robert Turner.
This study was funded by grants from the Alberta Cancer Foundation, Alberta Heritage Foundation for Medical Research (Alberta Innovates–Health Solutions) and the Canada Research Chair program.
Conflict of interest: The authors have no conflicts of interest to disclose.