Immunologic Monitoring with Cytomegalovirus (CMV) ELISPOT for Prediction of Recurrent CMV Infection and Late-onset CMV Disease in Pediatric Allogenic Hematopoietic Stem Cell Transplant (HSCT) Recipients

Abstract

Background

CMV-specific immunity is a well-known predictor for the increased risks of recurrent or persistent CMV reactivation and CMV disease. We tried to evaluate the clinical usefulness of CMV immune monitoring by ELISPOT assay which was relatively easy to standardize to implement the T cell immune monitoring in a routine clinical setting of pediatric allogenic HSCT.

Methods

From March 2016 through February 2017, children ≤18 years of age receiving allogeneic HSCT at Asan Medical Center were prospectively enrolled. All subjects underwent CMV pp65 and IE1-specific ELISPOT assays just before transplantation and then monthly until detection of CMV-specific T cells by > 5 spots/2.0 x 10⁵ cells. Viral load monitoring was performed as a routine practice. We analyzed the risk factor for the clinically significant CMV burden including recurrent CMV infection, late onset CMV infection and tissue-invasive CMV disease.

Results

A total of 40 CMV-seropositive recipients including 24 haploidentical donor HSCT were enrolled. CMV reactivation was observed in 22 patients and median time to initial CMV reactivation was 36 days (range, 17–125 days). Overall, 31 patients recovered CMV-specific immunity at a median of 34 days post SCT (range, 25–173 days) and 70.0% of recipients showed CMV-specific ELISPOT response at 90 days. Recipients with no ELIPSOT response during the follow-up period were younger than those with positive response (5.4 vs. 10.0 years of age; P = 0.026) and the presence of chronic graft vs. host disease (cGvHD) was the only significant factor for recovery of CMV specific immunity (adjusted hazard ratio [aHR] 8.803; P = 0.036). Recurrent CMV infection, late-onset CMV infection, CMV disease was observed in 1, 2, and 3 recipients, respectively. Recipients with clinically significant CMV burden was associated with younger age, the use of GvHD prophylaxis, prolonged CMV viremia of >2 weeks, and absence of CMV ELISPOT response before HSCT; the presence of cGvHD had the most significant influence on the clinically significant CMV burden (aHR 16.25, P = 0.024).

Conclusion

Among pediatric allogenic HSCT recipients, significant burden of CMV infection was observed, which was associated with development of cGVHD. The usefulness of the CMV ELISPOT assay along with viral load monitoring should be confirmed in a large-scale trial.

Disclosures

All authors: No reported disclosures.

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2xfVTcs
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