Abstract 2248

Poster Board II-225

Background:

Anti-CMV T-cells are thought to control CMV. In seropositive recipients of grafts from seropositive donors (D+R+), both na•ve and memory/effector anti-CMV T-cells are transferred with the graft. In seropositive recipients of grafts from seronegative donors (D-R+), only na•ve anti-CMV T-cells are transferred with the graft. We hypothesized that counts of anti-CMV T-cells are higher in the D+R+ compared to the D-R+ group, and that this leads to a lower incidence of CMV complications like CMV disease or CMV reactivation treated with toxic antiviral drugs, and that this may be particularly obvious in the setting of T cell depletion.

Patients and methods.

We reviewed charts of 298 seropositive recipients for CMV reactivation (pp65 antigenemia or CMV DNAemia above institutional threshold for starting preemptive therapy), recurrent CMV reactivation (above the same threshold), CMV disease, and death due to any cause. In 76 of these patients, we determined the counts of anti-CMV effector T-cells (producing INFg upon 18 h stimulation with CMV lysate in case of CD4+ T-cells or pp65 overlapping peptides in case of CD8 T+-cells). Conditioning of all patients included rabbit-anti-human thymocyte globulin (Thymoglobulin). Median follow up of the 298 patients was 19.6 months (range, 0.3 – 120.6)

Results.

As shown in Table 1, the anti-CMV T cell, in particular, CD4+ T-cell counts were higher, and the cumulative incidences of CMV reactivation, recurrent CMV reactivation and CMV disease were lower in D+R+ compared to D-R+ patients. Conclusion. Compared to D+R+ patients, D-R+ have lower counts of anti-CMV T-cells. This appears to translate into a higher risk of CMV reactivation and CMV disease. New strategies to avoid CMV complications need to be explored for D-R+ patients, eg, donor vaccination pre-transplant or infusion of anti-CMV T-cells post-transplant.

Table 1

Comparison of D+R+ and D-R+ patients

Anti-CMV T-cell countD+R+ n= 45D-R+ n=31P-value
CMV-specific CD4 T cells per ml (median) 
Day 28 1.50 0.10 0.048** 
Day 56 5.23 0.56 0.005** 
Day 84 8.19 1.27 <0.001** 
Day 180 6.26 0.32 0.002** 
Anti-CMV T-cell countD+R+ n= 45D-R+ n=31P-value
CMV-specific CD4 T cells per ml (median) 
Day 28 1.50 0.10 0.048** 
Day 56 5.23 0.56 0.005** 
Day 84 8.19 1.27 <0.001** 
Day 180 6.26 0.32 0.002** 
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Pp65-specific CD8 T cells per ml (median)
Day 28 0.81 0.03 0.04TF-1* 
Day 56 12.16 1.49 0.03* 
Day 84 11.26 2.77 0.11* 
Day 180 3.87 2.67 0.60* 
Clinical Outcomes D+R+ n= 171 D-R+ n=121 P-value  
CMV reactivation above threshold for preemptive therapy (No. of patients with at least one reactivation, (%)) 36 (20.3%) 58 (48.7%) <0.001** 
Recurrent CMV reactivation (No. of patients with at least 2 reactivations, (%)) 7 (3.9%) 19 (15.9%) 0.001** 
CMV disease (No. of patients, (%)) 5 (2.8%) 16(13.3%) 0.003** 
Pp65-specific CD8 T cells per ml (median)
Day 28 0.81 0.03 0.04TF-1* 
Day 56 12.16 1.49 0.03* 
Day 84 11.26 2.77 0.11* 
Day 180 3.87 2.67 0.60* 
Clinical Outcomes D+R+ n= 171 D-R+ n=121 P-value  
CMV reactivation above threshold for preemptive therapy (No. of patients with at least one reactivation, (%)) 36 (20.3%) 58 (48.7%) <0.001** 
Recurrent CMV reactivation (No. of patients with at least 2 reactivations, (%)) 7 (3.9%) 19 (15.9%) 0.001** 
CMV disease (No. of patients, (%)) 5 (2.8%) 16(13.3%) 0.003** 
*

Univariate analysis (Mann-Whitney-Wilcoxon rank-sum test)

**

Multivariate analysis (Generalized linear model) including the following covariates: HLA-matched sibling graft, significant graft versus host disease (GVHD) (grade 2-4 acute or extensive chronic GVHD), disease stage and graft product (bone marrow vs peripheral stem cells)

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Disclosures:

No relevant conflicts of interest to declare.

Topics:
antiviral agents, cmv reactivation, cytomegalovirus, donors, follow-up, globulins, graft-versus-host disease, graft-versus-host disease, chronic, human leukocyte antigens, immunity

Author notes

*

Asterisk with author names denotes non-ASH members.

© 2009 by The American Society of Hematology
2009
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