Background: Cytomegalovirus (CMV) infection increases mortality and morbidity following allogeneic hematopoietic stem-cell transplantation (alloHSCT). Universal antiviral prophylaxis with letermovir is effective but unsubsidized in Australia. Valaciclovir demonstrates anti-CMV activity in high doses, but few current real-world studies explore its use as primary prophylaxis in high-risk patients post-alloHSCT. Methods:We performed a retrospective analysis of alloHSCT recipients at high risk of clinically significant CMV infection (cs-CMVi), defined as a plasma CMV DNA viral load of >400 IU/ml requiring preemptive therapy, or CMV disease. High-risk recipients were CMV seropositive and underwent T-cell depleted, haploidentical or umbilical cord stem-cell transplants. Consecutive patients transplanted from July 2018 to January 2020, treated with valaciclovir 2 g TDS from day +7 to +100 (HD-VALA), were compared to a historical cohort (July 2017-June 2018) who only received preemptive CMV therapy, and standard valaciclovir (SD-VALA) for varicella/herpes prophylaxis. We compared incidence of and time to cs-CMVi. Results:In the SD-VALA cohort (n = 27, median CMV follow-up duration 259 days), 23/27 (85%) developed cs-CMVi at a median of 39 days. For the HD-VALA cohort (n = 35, median CMV follow-up duration 216 days), 19/35 (54%) developed cs-CMVi, at a median of 68 days. Time to cs-CMVi was significantly longer in HD-VALA cohort (p < .0001). On multivariate analysis, HD VALA reduced the risk of cs-CMVi (HR 0.32, p = .0005). Conclusions:In alloHSCT recipients at high risk for cs-CMVi, HD-VALA resulted in lower cumulative reactivation, and delayed reactivation, reducing requirement for preemptive CMV therapy in the early post-engraftment period.
Introduction Understanding the economic impact of managing allogeneic hematopoietic stem cell transplant (HSCT) recipients with cytomegalovirus (CMV) is important for future planning within institutional transplant programs. CMV remains the most frequent viral infection following HSCT of which the clinical impact on transplant outcomes has been well described. However, much less is known about the impact of CMV on health resource utilisation, re-admissions and hospital costs. In addition to antiviral therapy, there are nursing, medical and pharmacy costs to consider. We therefore undertook a study to evaluate the clinical and economic burden of CMV infection following HSCT in a large Australian transplant centre operating under a universal health care system. Methods A retrospective single centre study at the Royal Melbourne Hospital, Melbourne, Australia was performed on all consecutive allogeneic HSCT recipients between January 2015 to December 2017. CMV pre-emptive monitoring using quantitative CMV plasma viral load was performed twice weekly from time of transplant to 100 days or longer in the presence of graft versus host disease. Clinically significant CMV (csCMV) was defined as patients receiving anti-CMV treatment, often with a plasma CMV viral load >400 IU/ml. Throughout the study period, the first line anti-CMV therapy was ganciclovir; either as oral valganciclovir for outpatient management in asymptomatic patients or IV ganciclovir as an inpatient for patients with concerns about oral absorption. Second-line therapy was IV foscarnet. Hospital costing data for the first and subsequent re-admissions for the first 12 months were obtained from the business intelligence unit. Financial year costing was available for FY2015/2016 to FY2017/2018. Ethics was approved by the Melbourne Health Human Ethics Review Committee (HREC 2017.368). Results A total of 255 patients underwent alloHSCT with a median age of 51 years (IQR 40-59) with the most common underlying diagnoses being AML (41%), ALL (11%) and MDS (11%) (Table 1). Thirty-one percent of transplants used myeloablative conditioning, 54% had unrelated donors and 3% had an umbilical cord source. Pre-transplant recipient CMV seropositivity was 62% (n=158), of whom 139 had detectable CMV viremia and 104 (40.8%) experienced clinically significant CMV (csCMV). The median duration of CMV treatment was 33 days (IQR 21-63). Re-admission to hospital within the first 12 months of HSCT occurred in 78.4%. There was a greater number of admissions observed in csCMV patients compared to no csCMV (median 3 vs 2 admissions, p=0.001) with the duration of admitted days within the first 12 months being significantly greater in csCMV patients compared to no csCMV (median 65 vs 36 days, p<0.00001). The mean total cost of treating patients with csCMV for the first 12 months compared to the total cost for patients not requiring CMV treatment was A$196,822 (US$147,616) and A$114503 (US $85,877) (p<0.0001), respectively. Therefore the crude attributable mean cost of treating csCMV was A$82,319 (US$61,739) per patient for the first 12 months of HSCT. The greatest significant contributory costs were from pharmacy A$17,807 (US$13,355), nursing A$16,944 (US$12,708) and medical A$5,898 (US$4,423). Conclusions The health care cost and resource utilisation of treating CMV infection following an allogeneic HSCT is substantial and places a heavy burden on limited health resources. In this study, patients experiencing csCMV had an increased number and longer total duration of admissions days compared to patients who did not require CMV treatment. Interventions aimed at reducing the burden of CMV in alloHSCT recipients are required. Disclosures Yong: Merck Ltd: Honoraria. Bajel:AbbVie: Membership on an entity's Board of Directors or advisory committees, Other: travel funding. Ritchie:Sanofi: Honoraria; Novartis: Honoraria; Imago: Research Funding; Beigene: Research Funding; Takeda: Research Funding; BMS: Research Funding; Pfizer: Consultancy; Amgen: Consultancy, Honoraria, Research Funding. Slavin:Merck Ltd: Honoraria, Research Funding.
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