The Impact of High CMV Viral Load and Refractory CMV Infection on Pediatric HSCT Recipients with Underlying Non-Malignant Disorder

Abstract

Hematopoietic stem cell transplantation (HSCT) is a curative therapy for an increasing number of nonmalignant indications. Its use is restricted by severe transplant-related complications, including CMV infection; despite various prophylactic and therapeutic strategies, CMV reactivation has remarkable morbidity and mortality. The analysis included 94 children with nonmalignant disorder who underwent allogeneic HSCT in the Department of Pediatric Hematology, Oncology, and Bone Marrow Transplantation in Wrocław during years 2016–2020. Twenty-seven (29%) children presented with CMV infection, including ten (10/27; 37%) with high level CMV viremia (10,000 copies/mL). Six patients experienced subsequent CMV reactivation. The first-line ganciclovir-based (GCV) treatment was insufficient in 40% (11/27) of children. Overall survival (OS) was significantly lower in children with high CMV viremia compared to those with low levels/no CMV [1yrOS High CMV = 0.80 (95% CI 0.41–0.95) vs. 1yrOS others = 0.96 (95% CI 0.89–0.99)]. Similarly, patients with resistant and recurrent infections had greater risk of death. CMV reactivation at any level relevantly prolonged the hospital stay. CMV reactivation with high viremia load and resistant/recurrent CMV infections lead to a significant decrease in OS in children with nonmalignant disorders treated with HSCT. Our data proves there is an urgent need to introduce an effective anti-CMV prophylaxis in this cohort of patients.

Refractory human cytomegalovirus infection without evidence of genetic resistance in the UL-54 and UL-97 genes in a pediatric hematopoietic stem cell transplant recipient: a case report

“…The presence of refractory infection constitutes a significant risk for the survival of infected patients (3 years event-free survival: 53% in cases of resistant CMV vs. 87% in cases of susceptible CMV; p < 0.001) (12). In the present case, a persistent viral load was observed during the 9 months post-HSCT, with an increase of 2.5-log 10 compared to the initial viral load of 688 copies/mL.…”

“…This is the first case reported in Peru and Latin America describing persistent CMV infection in a pediatric haploidentical HSCT recipient. CMV infection significantly increases morbidity in transplant patients and represents a major risk factor for survival (12). The incidence of CMV infection in individuals undergoing haploidentical HSCT is significantly higher than in those with matched sibling donors (MSD) or matched unrelated donors (MUD) (85.7%, 39.0%, 55.6%, respectively; p < 0.001) (13).…”

“…Refractory infections in HSCT recipients are usually common (12%) (12). Refractory CMV infection is characterized by a viremia increase of more than 1-log 10 after at least 2 weeks of antiviral treatment (8).…”

Circulating cytokine and chemokine patterns associated with cytomegalovirus reactivation after stem cell transplantation

“…As a subset of HR (6/15), but no LR, patients also had aGvHD, future studies with larger patient numbers should compare plasma cytokine profiles in high‐level reactivators with and without aGvHD, to determine specific signatures associated with these complications. It should also be noted that the viraemia threshold used to define high‐level HCMV reactivation varies between studies 26,51,52 . Finally, to minimise the number of statistical comparisons, we did not compare all pairs of patient groups ( e.g .…”

“…It should also be noted that the viraemia threshold used to define high‐level HCMV reactivation varies between studies. 26 , 51 , 52 Finally, to minimise the number of statistical comparisons, we did not compare all pairs of patient groups ( e.g . SN and SP‐NR).…”