Prevention Of Cytomegalovirus Disease Research Articles

Cytomegalovirus Management in Solid Organ Transplant Recipients: A Pre-COVID-19 Survey From the Working Group of the European Society for Organ Transplantation

Infections are leading causes of morbidity/mortality following solid organ transplantation (SOT) and cytomegalovirus (CMV) is among the most frequent pathogens, causing a considerable threat to SOT recipients. A survey was conducted 19 July–31 October 2019 to capture clinical practices about CMV in SOT recipients (e.g., how practices aligned with guidelines, how adequately treatments met patients’ needs, and respondents’ expectations for future developments). Transplant professionals completed a ∼30-minute online questionnaire: 224 responses were included, representing 160 hospitals and 197 SOT programs (41 countries; 167[83%] European programs). Findings revealed a heterogenous approach to CMV diagnosis and management and, sometimes, significant divergence from international guidelines. Valganciclovir prophylaxis (of variable duration) was administered by 201/224 (90%) respondents in D+/R− SOT and by 40% in R+ cases, with pre-emptive strategies generally reserved for R+ cases: DNA thresholds to initiate treatment ranged across 10–10,000 copies/ml. Ganciclovir-resistant CMV strains were still perceived as major challenges, and tailored treatment was one of the most important unmet needs for CMV management. These findings may help to design studies to evaluate safety and efficacy of new strategies to prevent CMV disease in SOT recipients, and target specific educational activities to harmonize CMV management in this challenging population.

Among CMV-positive renal transplant patients receiving non-T-cell depleting induction, the absence of CMV disease prevention is a safe strategy: A retrospective cohort of 372 patients.

Cytomegalovirus (CMV) is the most common opportunistic pathogen affecting renal transplant recipients, especially in the first months. CMV-seropositive renal transplant recipients (CMV R+) are at intermediate risk for CMV disease, but this risk is enhanced among CMV R+ receiving T-cell depleting induction, compared to CMV R+ receiving non-depleting induction. In this second group, data in favor of prophylactic antiviral treatment with valganciclovir to reduce CMV disease is sparse. In this retrospective and multicentric trial, we included 372 CMV R+ transplanted between January 2012 and April 2015 and receiving non-depleting induction. During the first year following transplantation, CMV disease occurred in 5/222 patients (2.25%) in the prophylaxis group and 9/150 (6%) in the no-prophylaxis group (difference +3.7; 95% CI: 0.5-8; P=.002 for non-inferiority). The incidence of allograft rejection and other infectious diseases was similar between the two groups. Graft and patient survival were similar at the end of follow-up. In conclusion, the absence of prophylaxis did not appear to have a deleterious effect for CMV diseases among CMV R+ receiving non-depleting induction.

“Low Dose Ganciclovir for Cytomegalovirus Reactivation after Allogeneic HSCT Is a Feasible Option with Same Efficacy and Less Toxicity Than Regular Dose”

Background: Cytomegalovirus (CMV) reactivation after allogeneic hematopoietic stem cell transplantation (HSCT) occurs in approximately 70% of seropostive patients. CMV reactivation is associated with higher non-relapse mortality (NRM) and worse overall survival (OS). Although preemptive therapy effectively prevents CMV disease, toxicity of ganciclovir (GCV), valganciclovir (VGCV), and foscarnet is a major concern. While GCV 5 mg/kg BID (regular dose) is the most commonly used regimen, some series have suggested that a lower dose (5mg/kg QD, lower dose) could be an option. Objectives: To compare two different regimens of ganciclovir (regular vs. lower dose) for preemptive CMV therapy. Patients and Methods: This was an observational, retrospective study in adult patients who underwent HSCT between April 2007 and April 2020 in two centers. Doses of ganciclovir were determined at the discretion of the transplant physician. The primary endpoint was CMV clearance (rate and time to) between the two preemptive strategies. Results: We analyzed 118 consecutive patients. The median age was 50 years, acute leukemia was the most frequent underlying disease (59%), and most patients received transplants from alternative donors (matched unrelated in 32% and haploidentical in 36%), after reduced-intensity conditioning regimens (76%), with peripheral blood as the source of stem cells (73%). T-cell depletion was performed in 31% (ATG in 29%, alemtuzumab in 2%). In total there were 174 CMV reactivations: 124 (71%) were treated with the regular dose, and 50 (29%) in an outpatient setting with low dose. The median time to CMV clearance was similar between regular and low dose of GCV (15 days vs. 18 days, respectively, p=0.88). The cumulative incidence (CI) of CMV clearance at 30 days was 83% in the regular dose and 88% in the lower dose (p=0.82). By multivariate analysis, correcting for the differences between the groups, the GCV regimen did not influence the time to CMV clearance (hazard ratio 0.94, 95% confidence interval 0.70 - 1.26). On the other hand, hematologic toxicity was more frequent in the regular dose, with more cases of both grade 3-4 neutropenia (59% vs. 33%, respectively, p=0.002) and thrombocytopenia (77% vs. 48%, respectively, p<0.0001). Ten patients had CMV disease and were treated with GCV 5mg/kg BID for 21 days. Conclusion: Our findings suggest that the use of GCV once daily was safe, less toxic, and may be less expensive, considering that most patients will receive the regimen in an outpatient basis. These data should be confirmed in a prospective trial. Disclosures No relevant conflicts of interest to declare.

Preemptive Therapy to Prevent CMV Disease in Liver Transplant Recipients

Most transplant centers employ one of two cytomegalovirus (CMV) prevention strategies. In universal prophylaxis, all at-risk recipients receive

The Development of Therapeutics for the Treatment and Prevention of CMV Disease in the Transplant Population: A Regulatory Perspective.

Cytomegalovirus (CMV) remains an important pathogen in the transplant population. As such, the US Food and Drug Administration has published a guidance to encourage and inform the development of therapeutics for the treatment and prevention of CMV disease in this population. This review summarizes important phase 3 trial design considerations for industry and provides rationale for some of the recommendations included in the guidance.

Evaluation of an electronic, patient-focused management system aimed at preventing cytomegalovirus disease following solid organ transplantation.

Cytomegalovirus (CMV) infection is common among solid organ transplant (SOT) recipients and may cause CMV disease. To optimize the implementation of existing prevention strategies, the Management of Post-transplant Infections in Collaborating Hospitals (MATCH) program was developed. Two key performances of MATCH (diagnosing CMV infection at low viral load (VL) and before the onset of CMV disease) were assessed prior to, during and after the implementation of MATCH. The MATCH program included a personalized surveillance plan, prophylaxis and preemptive therapy determined by the recipient's risk of CMV infection. The plan was composed through predefined algorithms and implemented through harvesting of real-time data from medical records. Risk of CMV disease was compared for recipients transplanted during and after vs prior to the implementation of MATCH. Lung and non-lung transplants were analyzed separately. A total of 593, 349, 520, and 360 SOT recipients were transplanted before (2007-2010), during (2011-2012), early after (2013-2015), and late after (2016-2017) implementation of MATCH with an observed reduction of diagnostic VL (P<.001) over time. Risk of CMV disease was reduced among non-lung transplant recipients transplanted during (adjusted hazard ratios [95% CI] 0.15 [0.04-0.54], P=.003), early after (aHR 0.27 [0.11-0.63], P=.003), and late after (aHR 0.17 [0.06-0.52], P=.002) compared with prior to MATCH. No significant change was observed among lung transplants. Implementation of CMV preventive strategies through MATCH was associated with a reduced risk of CMV disease among non-lung transplant recipients. Furthermore, the limitations of VL as a sole indicator for CMV disease in lung transplants were emphasized.

Efficacy and safety of the combination of reduced duration prophylaxis followed by immuno-guided prophylaxis to prevent cytomegalovirus disease in lung transplant recipients (CYTOCOR STUDY): an open-label, randomised, non-inferiority clinical trial

IntroductionProlonged use of antivirals to prevent the development of cytomegalovirus (CMV) disease in lung transplant patients has been shown to have significant side effects, for which alternatives are being sought...

Cytomegalovirus prevention strategies and the risk of BK polyomavirus viremia and nephropathy.

Polyomavirus BK (BKV) is the cause of polyomavirus-associated nephropathy resulting in premature graft loss. There are limited data regarding the role of cytomegalovirus (CMV) infection and its prevention in developing BKV viremia and PVAN. In a prospective study, we analyzed 207 consecutive renal transplant recipients previously enrolled in 2 randomized trials evaluating different CMV prevention regimens with routine screening for BKV and CMV. Of these, 59 received valganciclovir and 100 valacyclovir prophylaxis; 48 patients were managed by preemptive therapy. At 3years, the incidence of BKV viremia and PVAN was 28% and 5%, respectively. CMV DNAemia developed in 55% and CMV disease in 6%. Both BKV viremia (42% vs 23% vs 21%, P=.006) and PVAN (12% vs 2% vs 2%, P=.011) were increased in patients treated with valganciclovir prophylaxis compared to valacyclovir and preemptive therapy. Using multivariate Cox proportional hazard regression, valganciclovir prophylaxis was independent predictor of BKV viremia (hazard ratio [HR]=2.38, P=.002) and PVAN (HR=4.73, P=.026). In contrast, the risk of subsequent BKV viremia was lower in patients with antecedent CMV DNAemia (HR=0.50, P=.018). These data suggest valganciclovir prophylaxis may be associated with increased risk of BKV viremia and PVAN. CMV DNAemia did not represent a risk for BKV.

Orphan designation: Brincidofovir, Prevention of cytomegalovirus disease

Orphan designation: Brincidofovir, Prevention of cytomegalovirus disease

Orphan designation: Covalently closed DNA plasmids coding for cytomegalovirus phosphoprotein 65 and glycoprotein B genes, Prevention of cytomegalovirus disease in patients with impaired cell-mediated immunity deemed at...

Orphan designation: Covalently closed DNA plasmids coding for cytomegalovirus phosphoprotein 65 and glycoprotein B genes, Prevention of cytomegalovirus disease in patients with impaired cell-mediated immunity deemed at...

Orphan designation: Covalently closed DNA plasmids coding for cytomegalovirus phosphoprotein 65 and glycoprotein B genes, Prevention of cytomegalovirus disease in patients with impaired cell-mediated immunity deemed at...

Orphan designation: Covalently closed DNA plasmids coding for cytomegalovirus phosphoprotein 65 and glycoprotein B genes, Prevention of cytomegalovirus disease in patients with impaired cell-mediated immunity deemed at...

Use of maintenance therapy and incidence of recurrent Cytomegalovirus DNAemia among allogeneic hematopoietic cell transplant recipients.

Cytomegalovirus (CMV) infection is the most common infection following hematopoietic cell transplantation (HCT). Preemptive antiviral therapy is highly effective at halting viral replication and preventing CMV disease; however, recurrence rates after clearance of CMV DNAemia are high (50-70%). Current treatment guidelines recommend maintenance therapy after initial clearance. Yet, the effectiveness of this intervention to prevent recurrence is not well defined. We aimed to assess the impact of maintenance therapy on the probability of recurrent CMV in allogeneic HCT recipients with early CMV reactivation. Sixty-six patients with an initial episode of early CMV reactivation who achieved viral clearance in response to preemptive therapy were included. We compared the incidence of recurrent CMV DNAemia in patients who received maintenance therapy vs those who underwent early discontinuation of antiviral therapy. Recurrence occurred in 47/64 (73%) patients, including 11/14 (79%) patients without maintenance therapy and 36/50 (72%) of patients who received maintenance therapy (P=0.74). The propensity score adjusted risk ratio for the effect of maintenance therapy on recurrence was 0.89 (95% CI 0.64-1.25; P=0.41). In a time to event analysis using the unweighted cohort, the 90-day probability of CMV recurrence was similar between patient groups independent of maintenance therapy administration (54% vs 64% for maintenance vs non-maintenance groups, respectively; log-rank P=0.37). These data suggest that maintenance antiviral therapy does not reduce the incidence of CMV recurrence while off therapy and is of limited value in HCT recipients who have successfully eradicated CMV DNAemia in response to preemptive therapy. Larger studies in this area are needed.

Cytomegalovirus (CMV) Pentameric Complex (PC) Neutralizing Antibodies (nAb) from a Randomized, Controlled Trial of CMV-Specific Intravenous Immunoglobulin (IVIG) for the Prevention of Primary CMV Infection after Hematopoietic Cell Transplantation (HCT)

Prevention of CMV disease after HCT remains a challenge. In addition to antivirals, immune-based strategies such as active and passive immunization may have potential roles preventing infection. CMV entry into epithelial and endothelial cells requires distinct viral proteins including UL128, UL130, UL131A, gB and gH/gL that combine to form a PC. A nAb assay was developed by Gerna et al. that measures nAb activity against PC, although its clinical application in HCT patients has not been described. In 1991, Bowden et al. conducted a study where CMV IVIG was administered as prophylaxis to D+/R- patients early after allogenic HCT. Although it showed reduced CMV infection in CMV IVIG recipients, CMV disease was not reduced thus its use was never adopted. This impact on infection suggests the possibility that CMV IVIG inhibits infection via neutralization of an unidentified entry pathway that may include PC. From the original cohort, we tested 538 serum samples from 61 patients using CMV DNA polymerase chain reaction (PCR) to compare clinically significant viral load (≥ 4 log10 IU/ml) or histopathologically detected CMV between groups. We also used a CMV nAb assay to evaluate anti-PC neutralizing capacity. The assay uses retinal pigmented epithelial (ARPE-19) cells exposed to serial dilutions of serum combined with a laboratory CMV strain, BADrUL131-Y4, that contains a green fluorescent protein (GFP) cassette. After one hour incubation, cells are washed and incubated for one week. Fluorescence is measured and we construct curves that plot viral neutralization against serum dilution and from these we extrapolate an IC-50; that is the dilution where 50% virus neutralization is achieved. After excluding three patients infected prior to day 21 post-transplant, there were 27 CMV IVIG and 31 control patients. Neither cumulative incidence of CMV infection (Figure 1, p=0.55), nor IC-50 values (Figure 2, p=0.19) differed by study arm, though observed median IC-50 values were higher in the CMV IVIG arm (5.8) than in the control arm (4.8). We found no association between IC-50 and risk of CMV infection (HR=1.8, 95% CI 0.6-5.3, p=0.31). Using modern CMV detection methods, our study suggests CMV IVIG does not result in decreased CMV viral load. Although the PC nAb composition of the CMV IVIG used is unknown, it did not appear protective against CMV infection. We successfully evaluated CMV PC entry-specific neutralizing activity in the HCT setting using a nAb assay, however evaluation among larger cohorts is needed to determine its clinical utility.

Determination of Optimal Viral Kinetic Markers for Predicting Antiviral Treatment Effect for the Prevention of Cytomegalovirus (CMV) Disease after Hematopoietic Cell Transplant (HCT) Using Machine Learning and a Novel Non-Parametric Estimation Method

The United States Food and Drug Administration recently issued guidance that CMV DNAemia (quantitative CMV viral load as measured by PCR) could be used in a composite endpoint along with tissue-invasive CMV disease as the primary endpoint in allogeneic HCT CMV prophylaxis trials. However, the specific time points after antiviral treatment initiation at which to measure viral load and the viral load thresholds that most accurately predict clinical CMV disease have not been identified. In order to estimate the treatment effect of an antiviral agent on CMV clinical outcomes, placebo-controlled, randomized trial data with accompanying viral load measurements are needed. Unfortunately, in the modern era of PCR and early preemptive treatment, ethically, placebo-controlled, randomized trials that allow for the development of CMV disease after HCT can no longer be performed. To overcome this limitation, we performed CMV DNA PCR testing on frozen plasma samples collected during the first 100 days post-HCT in the only placebo-controlled, double-blind RCT of ganciclovir for the early treatment of CMV infection after HCT (Goodrich et al. NEJM 1991). We used three analytic methods (Cox proportional hazards models, machine learning, and a novel non-parametric method) to determine which of 14 viral load markers, measured in the first four weeks of treatment, are the most useful surrogates of antiviral treatment for the prevention of CMV disease. All methods identified peak viral load and percentage of positive samples by week 4 as highly associated with or predictive of tissue-invasive CMV disease by week 8 post-randomization. Cox proportional hazards models (Figure 1) yielded significant associations for peak viral load measured by week 4 (HR 1.4, 95% CI 1.1-1.9) and percentage of positive samples by week 4 (HR 1.6, CI 1.1-2.3). The machine-learning ensemble algorithm SuperLearner implemented in R (Figure 2) demonstrated cross-validated area under the receiver-operator curves of at least 75% for peak viral load (75%, CI 62-87%) and percentage of positive plasma samples (77%, CI 63-90%) measured by week 4. Using a novel statistical technique that allows direct estimation of biomarker surrogacy (Parast et al. Stat Med 2017), we estimated that the percentage of ganciclovir treatment effect explained by peak viral load and percentage of positive samples measured by week 4 was greater than 85%—peak viral load 89%, CI 56-100%; percent positive samples 91%, CI 60-100% (Figure 3). Peak viral load and percentage of positive samples by week 4 are highly predictive of CMV disease and the treatment effect of ganciclovir. Our analysis suggests that these may be the best surrogate markers of ganciclovir treatment and introduces novel methods for identifying optimal candidate biomarkers as surrogates for clinical endpoints.

Use of Maintenance Therapy and Incidence of Recurrent CMV Dnaemia Among Allogeneic Hematopoietic Cell Transplant Recipients

Background Cytomegalovirus (CMV) infection is the most common infection following hematopoietic cell transplantation (HCT). Pre-emptive antiviral therapy is highly effective at halting viral replication and preventing CMV disease; however, recurrence rates after clearance of CMV DNAemia are high (50-70%). Current treatment guidelines recommend maintenance therapy after initial clearance. Yet, the effectiveness of this intervention to prevent recurrence is not well defined. Objectives We aimed to assess the impact of maintenance therapy on the probability of recurrent CMV in allogeneic HCT recipients with early CMV reactivation. Study design Sixty-six patients with an initial episode of early CMV reactivation who achieved viral clearance in response pre-emptive therapy were included. We compared the incidence of recurrent CMV DNAemia in patients who received maintenance therapy versus those that underwent early discontinuation of antiviral therapy. (Figure 1) Results Recurrence occurred in 47/64 (73%) patients, including 11/14 (79%) patients without maintenance therapy and 36/50 (72%) of patients who received maintenance therapy (P = 0.74). The propensity score adjusted risk ratio for the effect of maintenance therapy on recurrence was 0.89 (95%CI 0.64-1.25; P = 0.41). In a time to event analysis using the unweighted cohort, the 90-day probability of CMV recurrence was similar between patient groups independent of maintenance therapy administration (54 vs. 64% for maintenance vs. non-maintenance groups, respectively; log-rank P = 0.37). Conclusion This data suggests that maintenance antiviral therapy does not reduce the incidence of CMV recurrence and is of limited value in HCT recipients who have successfully eradicated CMV DNAemia in response to pre-emptive therapy. Larger studies in this area are needed.

Toxicities of CMV Preemptive Therapy in the First 100 Days after Allogeneic Hematopoietic Cell Transplantation (HCT): A Real-World Study at Memorial Sloan Kettering Cancer Center (MSKCC)

Background Cytomegalovirus (CMV) is the most common viral infection after HCT. Current antivirals used for preemptive therapy (PET) effectively prevent CMV disease, but their use is limited by toxicities. We examined real-world utilization patterns of PET and associated toxicities in HCT recipients at high risk (HR) and low risk (LR) for CMV through day (D) 100 post HCT. Methods Adult, CMV-seropositive first bone-marrow or peripheral blood HCT recipients from January 1, 2015 through December 31, 2017, routinely monitored by quantitative CMV PCR (Taqman, Roche) were analyzed. PET utilization including types and sequence of antivirals, dose and duration, and reasons for discontinuation through D 100 were extracted from medical records. HR included T-cell depleted HCT or conventional mismatched or haploidentical HCT. All other were LR. Descriptive statistics are reported. Results Of 232 patients (pts), 121 (52%) received PET including 40 LR and 81 HR. PET started at a median 35 D post HCT [HR vs. LR: 32 vs. 39, P Conclusions Valganciclovir was the preferred first line PET agent. HR pts had earlier initiation and longer PET duration. 1st PET discontinuation/change due to clinical or laboratory defined toxicity occurred commonly with similar frequency between HR and LR. Our findings support the need for more effective and safer PET alternatives for HCT recipients.

Application of a New Paradigm for Cytomegalovirus Disease Prevention in Mayo Clinic’s First Face Transplant

The optimal approach to preventing cytomegalovirus (CMV) disease after face transplant is unknown. We report an individualized hybrid approach, initially using valganciclovir prophylaxis followed by surveillance and preemptive therapy guided by viral and immunologic markers. A 31-year-old man received a near-total face allotransplant for gunshot injury–related severe facial deformities. He was CMV seronegative, and the donor was CMV seropositive (D+/R− mismatch), and he received intravenous ganciclovir followed by oral valganciclovir prophylaxis. Monthly CD8+ T-cell immune competence assay revealed no CMV-specific CD8+ T-cell immunity development during valganciclovir prophylaxis. Because of severe leukopenia, valganciclovir was discontinued at 7 months after transplant when the patient had recovered and sustained normal global CD8+ T-cell function. Weekly CMV polymerase chain reaction testing detected asymptomatic CMV replication (plasma CMV, 549 IU/mL) 3 months later. Short-course preemptive valganciclovir treatment resulted in sustained virologic clearance. The patient had development of CMV-specific CD8+ T cells (12 cells/μL) together with CMV IgM and IgG. No rejection or infection relapse was detected 20 months after transplant. In conclusion, viral and immunologic monitoring allowed for an individualized approach to effective CMV disease prevention after face transplant. This case highlights the importance of understanding the interplay between the host immunity and the pathogen in determining the clinical course and outcome of CMV and other infectious disease syndromes.

Treatment and Prevention of CMV Disease in Transplant Recipients: Current Knowledge and Future Perspectives.

This review summarizes the significant impact of cytomegalovirus (CMV) infection on solid organ and hematopoietic stem cell transplant recipients. A discussion of the various CMV prevention and treatment strategies is provided, including a detailed description of each of the available CMV antiviral drugs.

Post Transplant Prophylaxis with High Dose Valacyclovir through Day 100 Versus Day of Post Transplant Hospital Discharge Decreases Cytomegalovirus Reactivation in Adult Umbilical Cord Blood Transplant Recipients

Abstract Background: Cytomegalovirus (CMV) infection remains an important cause of morbidity and cost following umbilical cord blood transplantation (UCBT). While the introduction of letermovir represents a novel approach to CMV prophylaxis, optimal CMV management strategies remain controversial. An intensive strategy to prevent CMV disease including one week of pre-transplant ganciclovir followed by high-dose acyclovir or high-dose valacyclovir through day 100 reduced post-transplant CMV reactivation (Milano et al, Blood 2011), but this approach is costly and potentially challenging to administer. Insurance approval for outpatient high-dose valacyclovir is variable, and the pill burden of high-dose acyclovir for post-transplant patients may be unmanageable. A recent study demonstrates that the removal of pre-transplant ganciclovir does not decrease CMV reactivation rates (Hill et al, BBMT 2018). At our center we have attempted to implement the high intensity strategy described above, but for patients who are unable to obtain high-dose valacyclovir at hospital discharge, we have transitioned to standard dose 800 mg acyclovir twice daily. Additionally, in November 2016, we discontinued pre-transplant ganciclovir. To examine the efficacy of these approaches, we compared CMV outcomes among these patients. Methods: All consecutive adult CMV seropositive (CMV R+) patients who received their first double UCBT from December 2009 to January 2018 were reviewed. Patients were excluded if they had initial CMV reactivation prior to day 0 or after day 100, graft failure, death or relapse before day 100, or participated in a CMV prophylaxis trial. Starting the day of transplant, CMV R+ patients received either valacyclovir 2 grams orally 3 times daily or acyclovir 500 mg/m2 intravenously every 8 hours until able to tolerate oral medication. At hospital discharge, patients for whom valacyclovir was authorized by insurance received valacyclovir 2 grams orally 3 times daily through day 100. All others received acyclovir 800 mg orally twice a day through day 100. No patients received anti-thymocyte globulin with conditioning. All patients transplanted prior to November 2016 received pre-transplant ganciclovir, after which pre-transplant ganciclovir was discontinued. CMV reactivation was defined as any detectable PCR positive whole blood sample (checked twice weekly through day 100). Thresholds for treatment with ganciclovir or foscarnet evolved over time, but required high initial copies levels, persistent or rising DNAemia, or evidence of end-organ involvement. Acute graft-versus-host-disease (aGVHD) treatment was based on institutional guidelines and uniform for all patients. Results: Demographics of the 101 patients studied are provided in table 1. Forty-one patients received prophylaxis with high-dose valacyclovir until post-transplant discharge only (median 23 days) and 60 received valacyclovir through day 100. Between day 0 and day 100, fewer patients in the high-dose valacyclovir group (n= 20, 36%) had CMV reactivation compared to those in the acyclovir group (n= 23, 57%), p= 0.025 (figure 1). Nine patients (9%) in the acyclovir group and 6 (6%) in valacyclovir group received CMV directed treatment (p= 0.1). Patients who did or did not received pre-transplant ganciclovir had similar rates of CMV reactivation (p= 0.55 in acyclovir arm, p= 0.15 in valacylcovir arm). Overall survival (p= 0.64), neutrophil and platelet engraftment time, and incidence of grade 2-3 (p= 0.7) and grade 3-4 aGVHD (p= 0.3) were comparable between groups. Conclusions: High-dose valacyclovir through day 100 post-transplant as compared to through the day of hospital discharge post-transplant reduced CMV reactivation rates. While threshold for treatment will vary according to institutional protocol, high-dose valacyclovir through day 100 likely reduces treatment episodes. One week of pre-transplant ganciclovir does not reduce CMV reactivation rates. These data provide important baselines for future comparisons of outcomes following letermovir prophylaxis in this population. Disclosures Haverkos: Viracta Therapeutics: Membership on an entity's Board of Directors or advisory committees.

1579. Evaluation of MATCH: an Electronic Individual Patient-Focused Management System Aimed at Preventing Cytomegalovirus Disease Following Solid Organ Transplantation

BackgroundCytomegalovirus (CMV) infection is common among solid-organ transplant (SOT) recipients and may cause CMV disease, if not promptly treated. Strategies to prevent CMV disease include chemoprophylaxis and pre-emptive monitoring and treatment of emerging subclinical infection. To optimize the implementation of these strategies as part of routine care, we developed and implemented a proactive and patient-tailored CMV management system for SOT patients (the MATCH program) in our center. Two key performance characteristics of success of MATCH are diagnosing CMV at low levels and avoiding CMV disease at diagnosis; these characteristics are assessed here before (2007–2010), during (2011–2012) and after (2013–2015) the implementation of the MATCH program.MethodsIn MATCH, SOT recipients follow a personalized, yet standardized, plan for monitoring, prophylaxis and pre-emptive therapy depending on underlying risk for CMV infection. The plan is composed in accordance with the recipient’s a priori risk as to CMV IgG serostatus and is continually updated during the post-transplant course according to patient′s current situation. Each individual patient plan is produced and implemented by a rule-based artificial intelligence (AI) platform, harvesting relevant real-time data from electronic medical records. Via predefined algorithms, plans and revisions are created and alerts are generated in case of missed planned monitoring for or molecular detection of CMV infection. Prior to its implementation, prevention of CMV disease was left at the discretion of the individual physician.ResultsA total of 603, 357, and 531 patients received an SOT before, during and after implementing MATCH, resp., of whom 88 (14.6%), 56 (15.7%) and 119 (22.4%) developed CMV infection within the first year of transplantation (Table 1). Among those with CMV infection, the % with high viral load decreased as did the % with CMV disease at the time of diagnosis of CMV infection during and after the implementation of MATCH relative to before (Figure 1). ConclusionThe implementation of a rule-based AI platform guiding routine prevention of CMV disease among SOT recipients was associated with improved CMV-specific outcome, indicating its ability to identify the CMV infection sooner after onset and before causing disease.Disclosures All authors: No reported disclosures.