Impact of cytomegalovirus infection prior to hematopoietic stem cell transplantation in children with inborn errors of immunity

Abstract

The presence of active viral infections has an impact on the prognosis of patients undergoing hematopoietic stem cell transplantation (HSCT). Nevertheless, the number of reports of cytomegalovirus infection in patients with inborn errors of immunity (IEI) who undergo HSCT is relatively low. To analyze the effect of cytomegalovirus infection acquired prior to curative treatment on patient survival in 123 children with IEI. An observational and retrospective study was performed with patients younger than 18 years diagnosed with IEI who were candidates for HSCT, gene therapy, or thymus transplantation at five hospitals in Spain between 2008 and 2019. We included 123 children, 25 infected by cytomegalovirus prior to undergoing curative treatment (20.3%). At IEI diagnosis, 24 of the patients were already infected, 21 of whom had symptomatic cytomegalovirus disease (87%), while the other three patients developed disease before undergoing curative treatment. The patients with cytomegalovirus infection had higher mortality than those without ( p = 0.006). Fourteen patients developed refractory cytomegalovirus infection (56%), all of whom died, while no patients with non-refractory infection died ( p = 0.001) All deaths that occurred before curative treatment and three of the five after the treatment were attributed to cytomegalovirus. Patients with refractory cytomegalovirus disease had the highest pre-HSCT mortality rate (64.3%), compared with the non-infected children and those with non-refractory cytomegalovirus disease (10.1%) ( p < 0.0001). Conclusion : Prevention and prompt control of cytomegalovirus infection, together with early HSCT/gene therapy, are crucial for improving the prognosis in children with IEI. What is Known: • Cytomegalovirus is the most frequent viral infection in children with inborn errors of immunity who are candidates to hematopoietic stem cell transplantation (HSCT). • Active viral infections at the time of HSCT lead to worse prognosis. What is New: • In children with inborn errors of immunity and indication of HSCT, refractory cytomegalovirus disease is associated with a very high mortality rate, compared with non-infected children and those with non-refractory cytomegalovirus disease. • In patients with novel transplantation indications, the presence and treatment response of CMV infection should be considered to decide the best possible moment for HSCT. Supplementary Information The online version contains supplementary material available at 10.1007/s00431-022-04614-5.

Letermovir for CMV prophylaxis in very high-risk pediatric hematopoietic stem cell transplantation recipients for inborn errors of immunity.

“…There is no data in infants and in patients with inborn errors of immunity (IEI). The latter group of patients are highly vulnerable to CMV infection and disease [19][20].We report in this monocentric, real-life study, the tolerance, e cacy and preliminary PK data of LMV for CMV prophylaxis in very high-risk pediatric HSCT recipients transplanted for IEIs.…”

“…There is no data in infants and in patients with inborn errors of immunity (IEI). The latter group of patients are highly vulnerable to CMV infection and disease [19][20].…”