Clinically Significant EBV Infection in Allogeneic Stem Cell Transplanted Children Receiving Letermovir as Primary CMV Prophylaxis.

Abstract

Background: Cytomegalovirus (CMV) infection and disease constitute an important complication of allogeneic hematopoietic stem cell transplantation with high morbidity. Letermovir prophylactic use in adult recipients has reduced the incidence of CMV infection with minimal toxicity. Relevant data on children is scarce, and letermovir has been used off-label. Recently, a couple of studies indicated an association of letermovir with EBV reactivation/PTLD in adults, raising a significant concern.

Methods: We aimed to retrospectively compare ultra-high-risk for CMV infection children with leukemia [seropositive children/seronegative donors], who received (LET-group) or did not receive (not LET-group) letermovir. Primary objectives were cumulative incidence (CI) of CMV reactivation, EBV reactivation, and clinically significant EBV infection (csEBVi).

Results: A total of 37 patients (median age 8.2 years), LET-group-11 and not LET-group-26, were included. The median follow-up was 34.3 months. Compared to the not LET group, patients of the LET group had a lower CI of CMV reactivation, 10% versus 38.4%, p = 0.07, a higher CI of EBV reactivation, 55%, referring to 6/11 patients, versus 23%, p = 0.07, and a higher CI of csEBVI, 40% (4/11 patients) versus 0%, p < 0.001. No patient in the LET group developed GvHD, compared to 23% for aGvHD p = 0.08 and 11.5% for cGvHD p = 0.25 in the non-LET group.

Conclusion: Our study confirms letermovir's effectiveness against CMV. Yet, it also reports a high incidence of EBV reactivation and significant EBV infection, as well as a reduced GvHD prevalence in children receiving the drug. Our single-center, retrospective analysis has major limitations but raises a concern. Our findings require further validation in larger, multicenter, prospective studies.