Incidence of CMV Reactivation and Infection in Children and Adolescents Following Allogeneic Hematopoietic Stem Cell Transplantation in High CMV Exposure Population

Introduction: Cytomegalovirus (CMV) infection is a known complication following allogeneic hematopoietic stem cell transplantation (HSCT). The method and duration of CMV monitoring are center-dependent, and no standards on the effective duration of CMV surveillance are clearly reported in the literature especially in areas with high CMV exposure. 

Patients and Methods: We retrospectively reviewed the medical records of all consecutive patients who received allogeneic HSCT between January 2008 and April 2014 at King Hussein Cancer Center (KHCC) in Jordan. The CMV infection was monitored using pp65 antigenemia test weekly from time of neutrophil engraftment until day 100 post transplantation. Treatment with gancyclovir was initiated when two consecutive positive antigenemia tests of more than two cells per 250 WBC were documented. All patients received leukofiltered and irradiated blood products.

Results: A total of 200 patients were identified, with median age of 9 year (2 months-27 year). Sixty percent (n=119) were males. One hundred and nineteen patients (60%) had non-malignant diseases. Peripheral blood (PB) was the stem cell source in 110 (55%), 69 (34.5%) received bone marrow and 21 patients (10.5%) received cord blood. Sixty nine percent received myeloablative conditioning (n=137), 26% reduced intensity (n=52) and 5% no conditioning regimen (n=11). Ninety-one percent (n=182) were matched-related (140 were HLA identical siblings and 42 were other family donors). Ninety three percent of our patients (n=186) and 83% of donors (n=166) were CMV sero positive. Thirty-five patients (17.5%) needed preemptive therapy for CMV reactivation at a median of 33 days (14-70) following transplantation. The median number of cells was one cell per 250 WBC (1-2298). Ten patients continued to have positive CMV antigenemia on day 70, and 3 on day 100, while only one patient had new episode of CMV reactivation after 70 days post transplantation. Two patients (1%) developed CMV disease (pneumnitis and colitis). In urivariate analysis, patients who received ATG (p=0.005), non-sibling related donors (p=0.037), mismatched or unrelated donor transplants (p=0.007), PB (p=0.019), and myeloablative conditioning (p=0.004) were at higher risk for developing CMV reactivation. In multivariate analysis; ATG use (HR=2.87; 95% CI 1.026-8.025; p=0.0445) and the use of mismatched related or unrelated donor (HR=11.11; 95% CI 1.87-66.67, p=0.0081) was associated with increased risk of CMV reactivation.

Conclusion: The incidence of CMV reactivation following allogeneic HSCT in children and adolescents within high CMV exposure population is low. Shortening the duration of CMV surveillance may be feasible. Use of ATG in the preparative regimen and those receiving mismatched or alternative donor transplants are at the highest risk for CMV reactivation.