Background: The use of lymphocyte depleting agents (LDA) for induction immunosuppression among renal transplant (tx) recipients raises concern for the increased susceptibility to viral infections, especially in the seronegative pediatric patients (ped pts). Here, we examine the rates of cytomegalovirus (CMV) viremia among ped pts receiving induction immunosuppression with LDA and non-LDA (NLDA) and assess their ability to mount CMV-Tc response.

Methods: Twenty-nine ped tx pts who received induction with either LDA (anti-thymocyte globulin or alemtuzumab) or NLDA (anti-IL-2R), maintained on mycophenolate mofetil (MMF), tacrolimus, with or without steroids, and had CMV-Tc testing by intracellular IFNg flow cytometry were included. Valganciclovir prophylaxis was given to all pts for the first 6 months (M) post-tx. CMV-PCR monitoring was performed monthly for the first 12M for CMV high risk group (D+/R-), and every 3M for all other groups. CMV-PCR cut off for positivity was >5 copies/PCR. All patients with CMV viremia underwent reduction of MMF by 30% with increase in valganciclovir to therapeutic doses.

Results: Twenty-three of 29 pts were CMV seronegative at the time of tx, 8 (34.8%) of which developed subclinical CMV viremia (median 93.5 copies/PCR; range 14-260), while none of the 6 seropositive pts developed viremia (p=0.09). Among the seronegative pts, 7 of 12 LDA developed viremia, compared to only 1 of 11 NLDA (p=0.013). Median time to develop viremia was 4.9M (range 1.0-8.2) in the LDA group and 7.1M among the 1 pt in the NLDA group. Median time between viremia and CMV-Tc testing was 8M (range 0.6-57.2). Six of the 7 (85.7%) LDA with viremia developed CMV-Tc, while 1 (14.3%) did not even after 21M post-infection. The 1 NLDA pt with viremia had recurrence of viremia 50M after initial viremic episode and could not develop CMV-Tc even after 57M post-initial infection. No pts developed CMV disease.

Conclusion: CMV seronegative ped pts receiving LDA induction are more likely to develop subclinical CMV viremia despite valganciclovir prophylaxis. However, most of these pts could develop CMV-Tc as early as 0.6M post-viremia. Early development of CMV-Tc may prevent development of CMV disease and CMV recurrence in this pt cohort. Monitoring CMV-Tc might help for better management of CMV infection in this pt population. Larger studies are needed to validate the role of CMV-Tc in preventing CMV disease.

CITATION INFORMATION: Pizzo H., Shin B., Toyoda M., Jordan S., Puliyanda D. CMV Viremia and Development of CMV-Specific Cytotoxic T-Cells (CMV-Tc) in Pediatric Renal Transplant Recipients Am J Transplant. 2017;17 (suppl 3).

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