Incidence of CMV Infection and Disease and Adverse Events Associated with Antiviral Therapy in a Retrospective Cohort of Allogeneic Hematopoietic Cell Transplant Recipients at an Academic Children’s Hospital

Abstract

Background Cytomegalovirus (CMV) is a significant source of morbidity and mortality among transplant recipients; the epidemiology is less understood in pediatric hematopoietic cell transplantation (HCT) cohorts. Furthermore, there is a paucity of data related to CMV prophylactic and preemptive strategies. Methods A single-center retrospective observational cohort of allogeneic HCT recipients at the Children’s Hospital of Philadelphia January 1, 2004–December 31, 2017 was constructed. Subjects were followed for 180 days after transplant to determine whether they had CMV infection or disease. Data on antiviral therapy were collected as were outcomes of CMV disease and adverse events (AEs) related to the antiviral therapy. Results Between January 2004 and March 2017, 345 allogeneic HCTs in 333 patients undergoing CMV surveillance testing were identified. CMV DNAemia was detected during the 180-day follow-up in 89 (25.8%) HCTs. CMV recipient-positive transplants were most likely to have CMV infection (47%). Infection rates were high for those receiving a CMV-specific prophylaxis regimen (50%). CMV DNAemia progressed to CMV disease 11.2% of the time. Of 224 subjects receiving CMV-specific prophylaxis, 19.2% experienced ≥1 AE. Of 53 receiving preemptive therapy during any CMV DNAemia episode, 32.1% experienced ≥1 AE. Conclusions CMV infection is common in pediatric allogeneic HCT recipients. The CMV-specific prophylaxis regimen employed in this cohort did not effectively prevent DNAemia, progression to CMV disease was uncommon, and AEs from prophylaxis and preemptive therapy were frequent. Novel approaches that reduce the impact of CMV on pediatric allogeneic HCT recipients are needed.

Evaluation of Platelet Parameters in Patients With Secondary Failure of Platelet Recovery and Cytomegalovirus Infection After Hematopoietic Stem Cell Transplantation

“…CMV infection is the most common infectious complication after HSCT, with an incidence of 30% to 50% . 20 Studies have shown that CMV infection can damage hematopoietic progenitor cells and the hematopoietic microenvironment, leading to myelosuppression and altered hematopoietic reconstitution. 21 At the same time, anti-CMV therapeutics such as ganciclovir and valganciclovir inhibit bone marrow hematopoiesis, resulting in an increased risk of SFPR.…”

Risk Factors for CMV Viremia and Treatment-Associated Adverse Events Among Pediatric Hematopoietic Stem Cell Transplant Recipients

“…Our findings confirm the importance of CMV seropositivity in pediatric HSCT recipients while suggesting that R+/D+ serostatus transplants may have a particularly high risk of CMV viremia. Other pediatric studies have reported a high risk of CMV infections among R+/D+ transplants compared with transplants with other serostatus combinations [ 9 , 27 ], suggesting that donor CMV seropositivity may be less protective against CMV viremia in children than in adults [ 28 ]. Taken together, our findings of CMV viremia in children after HSCT can inform optimal CMV serostatus recipient–donor pairings and CMV prophylaxis strategies.…”

Effect of cytomegalovirus infection on post‐transplant hospitalization days among children undergoing allogeneic hematopoietic cell transplantation: A marginal structural model approach

“…At CHOP, there was no lower limit to the threshold for quantification of CMV DNAemia prior to November 2014. Additionally, the units ‘copies/mL’ was used for CMV PCR reporting from whole blood testing as previously described 8 . In November 2014, the lower limit for quantification of a positive whole blood CMV PCR was set at 3.11 log IU/mL, as values less than this may not be reliably detected or reproducible.…”

“…Pre‐existing data from a previously described retrospective observational cohort of allogeneic HCT recipients at the Children's Hospital of Philadelphia (CHOP) between January 2004 and April 2017 8 were used for this study. Patients were eligible for the cohort if they were initiated on CMV surveillance testing protocol following HCT, defined as having ≥2 whole blood CMV polymerase chain reaction (PCR) tests in the first month after HCT regardless of pre‐transplant donor/recipient (D/R) CMV status.…”

“…Acyclovir or foscarnet based prophylaxis regimens have been employed but these agents are associated with toxicity and their effectiveness has not been clearly documented. 8 Letermovir, a novel anti-CMV agent, was effective at reducing CMV DNAemia rates in adult HCT recipients at high-risk for CMV reactivation and had a reassuring safety profile. 10 However, pediatric guidelines note that pediatric specific efficacy data are needed before endorsing letermovir prophylaxis in children.…”