scholarly journals 2646. Incidence of Myelosuppression Related to Valganciclovir Prophylaxis in Solid-Organ Transplant Recipients at High Risk of CMV Disease

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S925-S926
Author(s):  
Sara Belga ◽  
Cristina Hernandez ◽  
Dima Kabbani ◽  
Carlos Cervera

Abstract Background Valganciclovir (VGCV) prophylaxis in solid-organ transplant patients (SOT) is limited by myelotoxicity. We aimed to analyze the impact of VGCV prophylaxis on myelotoxicity and risk factors for its occurrence. Methods Retrospective single-center cohort study of adult CMV-seronegative recipients transplanted between July 2005 and November 2017. CMV D+/R− recipients received 3 to 6 months of VGCV prophylaxis whereas CMV D-/R- received no VGCV. Definitions: leukopenia < 3.5 × 109/L, significant neutropenia < 1.0 × 109/L and significant thrombocytopenia < 50 × 109/L. Results A total of 363 SOT recipients were included, 169 (47%) CMV D+/R− and 194 (53%) CMV D−/R−, with a mean age of 49.5 years and 275 (76%) males; types of organ transplant: 133 (37%) liver, 181 (50%) kidney, 37 (10%) simultaneous kidney-pancreas and 12 (3%) other. Although there was no difference in the incidence of significant neutropenia or thrombocytopenia per transplant type, leukopenia in the first year was more common in liver transplant patients (P < 0.001). New onset leukopenia post-SOT, significant neutropenia (Figure 1) and significant thrombocytopenia in the first year were more common in patients receiving VGCV: 116 D+/R− (69%) vs. 52 D−/R− (31%), P < 0.001; 86 (91%) vs. 9 (9%), P < 0.001; 8 (80%) vs. 2 (20%), P = 0.050; respectively. G-CSF was used more frequently in patients receiving prophylaxis (60% CMV D+/R− vs. 10% CMV D−/R−, P < 0.001). Significant neutropenia had no impact on long-term mortality adjusted by age and transplant type (HR 1.1, 95% CI 0.6–2.1, P = 0.709). Significant neutropenia led to decrease immunosuppression in 90% of patients (vs. 46%, P < 0.001) and was associated with increased risk of rejection (HR 8.5, P < 0.001). In multivariate analysis for significant neutropenia in the first year, VGCV prophylaxis was the only predictor of this outcome after adjusting for confounders (HR 15.1, 95% CI 7.5–30.1, P < 0.001). Conclusion VGCV prophylaxis increased the risk of significant neutropenia by 15-fold post-SOT. No other clinical variables were useful to predict this complication. Therefore, complete blood count monitoring is still needed for all SOT recipients receiving VGCV prophylaxis. Disclosures All authors: No reported disclosures.

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S481-S482 ◽  
Author(s):  
Bradley Gardiner ◽  
Jennifer Chow ◽  
Sam Brilleman ◽  
Anton Peleg ◽  
David Snydman

2021 ◽  
Vol 7 (5) ◽  
pp. 327
Author(s):  
Nipat Chuleerarux ◽  
Achitpol Thongkam ◽  
Kasama Manothummetha ◽  
Saman Nematollahi ◽  
Veronica Dioverti-Prono ◽  
...  

Background: Cytomegalovirus (CMV) and invasive aspergillosis (IA) cause high morbidity and mortality in solid organ transplant (SOT) recipients. There are conflicting data with respect to the impact of CMV on IA development in SOT recipients. Methods: A literature search was conducted from existence through to 2 April 2021 using MEDLINE, Embase, and ISI Web of Science databases. This review contained observational studies including cross-sectional, prospective cohort, retrospective cohort, and case-control studies that reported SOT recipients with post-transplant CMV (exposure) and without post-transplant CMV (non-exposure) who developed or did not develop subsequent IA. A random-effects model was used to calculate the pooled effect estimate. Results: A total of 16 studies were included for systematic review and meta-analysis. There were 5437 SOT patients included in the study, with 449 SOT recipients developing post-transplant IA. Post-transplant CMV significantly increased the risk of subsequent IA with pORs of 3.31 (2.34, 4.69), I2 = 30%. Subgroup analyses showed that CMV increased the risk of IA development regardless of the study period (before and after 2003), types of organ transplantation (intra-thoracic and intra-abdominal transplantation), and timing after transplant (early vs. late IA development). Further analyses by CMV definitions showed CMV disease/syndrome increased the risk of IA development, but asymptomatic CMV viremia/infection did not increase the risk of IA. Conclusions: Post-transplant CMV, particularly CMV disease/syndrome, significantly increased the risks of IA, which highlights the importance of CMV prevention strategies in SOT recipients. Further studies are needed to understand the impact of programmatic fungal surveillance or antifungal prophylaxis to prevent this fungal-after-viral phenomenon.


2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S639-S639
Author(s):  
Anna Sharova ◽  
Despoina M Galetaki ◽  
Molly Hayes ◽  
Lauren Gianchetti ◽  
Laura A Vella ◽  
...  

Abstract Background Our institution provides universal CMV prophylaxis (PPX) for all high (D+/R-) and medium risk (R+) solid-organ transplant (SOT) recipients. We sought to evaluate this practice by assessing CMV infection and disease within the first year of SOT. Methods Retrospective cohort study of all children undergoing first SOT at Children’s Hospital of Philadelphia from January 2012 to October 2017. We identified recipients with CMV infection (detection of CMV DNA in body fluid/tissue with or without symptoms) and disease (symptomatic or tissue-invasive infection) in the first year after SOT. We calculated the rate of CMV infection and compared CMV-free survival based on SOT type and CMV risk using log-rank tests. Results 244 children received 246 SOTs: 90 liver, 70 kidney, 59 heart, 27 lung. In total, 39 children (16%) had 49 CMV infections in the first year after SOT, including 29% of high (n = 21/72) and 23% of medium risk recipients (n = 16/69). The fraction of each organ type with CMV infection was similar (Figure 1, P = 0.33). Among high and medium risk recipients, all of whom received PPX, the incidence rate of CMV infection in the first year post-SOT was similar: 10.1 vs. 7.8/10,000 days (P = 0.22). There were no differences in CMV-free survival by organ (Figure 2, log-rank P = 0.25) or between high and medium risk recipients (Figure 3, log-rank P = 0.46). In total, 22% (n = 10/45) of CMV infections in high/medium risk patients occurred while on PPX; half were in the setting of reduced PPX dosing or within 2 weeks of SOT. Of the 35 CMV infections post-PPX, the median time to detection of CMV after PPX was 39 days (IQR 28–98). There were 11 cases (6 high, 5 medium risk) of CMV disease: 6 CMV syndrome, 2 hepatitis, 2 pneumonitis, 1 GI disease. Valganciclovir was more often used for treatment of asymptomatic infections than for CMV disease (79% vs. 33%, P = 0.03). All-cause mortality in the first year post-SOT was similar among those with and without CMV infections (7.7 vs. 6.3%, P = 0.76) and among those with and without CMV disease (9.1 vs. 5.2%, P = 0.57). Conclusion CMV infection was common in high and medium risk SOT recipients in the first year following SOT, and most infections occurred off of PPX. Our data suggest that the highest risk period for CMV infection is in the first months after PPX, and that monitoring may be most useful after PPX has been stopped or when PPX doses are reduced. Disclosures Kevin J. Downes, MD, Merck: Grant/Research Support, Research Grant; Pfizer: Grant/Research Support.


2018 ◽  
Vol 39 (5) ◽  
pp. 563-570 ◽  
Author(s):  
Ruihong Luo ◽  
Janice M. Weinberg ◽  
Tamar F. Barlam

OBJECTIVEClostridium difficileinfection (CDI) is common in solid organ transplant (SOT) recipients, but few studies have examined long-term outcomes. We studied the impact of CDI after SOT on mortality and transplant organ complication-related hospitalizations (TOH).METHODSSOT recipients ≥18 years of age with at least 1 year of posttransplant data were analyzed using the MarketScan database for 2007–2014. Patients who died within one year of transplant were followed until death. Patients were grouped as early CDI (ie, first occurrence ≤90 days posttransplant), late CDI (ie, first occurrence >90 days posttransplant) and controls (ie, no CDI occurrence during follow-up). The risk of mortality or TOH after CDI was evaluated using Cox and logistic regressions, respectively.RESULTSOverall, 96 patients had early CDI, 97 patients had late CDI, and 5,913 patients were used as controls. The risk for death was significantly higher in the early CDI group than the control group (hazard ratio [HR],1.92; 95% confidence interval [CI], 1.12–3.29;P=.018); there was no significant difference between the late CDI group and the control group (HR, 0.86; 95% CI, 0.38–1.94;P=.717). Both the early CDI group (odds ratio [OR], 2.19; 95% CI, 1.45–3.31;P<.001) and the late CDI group (OR, 4.36; 95% CI, 2.84–6.71;P<.001) had higher risk for TOH than the control group. For those patients who survived >90 days posttransplant, both the early CDI group (n=89) and the late CDI group (n=97) had increased risk for death or TOH during follow-up than the control group (n=5,734).CONCLUSIONThough our study could not prove causality, both early and late CDI occurrence in SOT recipients were associated with worse future outcomes than for SOT recipients without CDI.Infect Control Hosp Epidemiol2018;39:563–570


2018 ◽  
Vol 18 (11) ◽  
pp. 2772-2780 ◽  
Author(s):  
Renana Yemini ◽  
Eviatar Nesher ◽  
Janos Winkler ◽  
Idan Carmeli ◽  
Carmil Azran ◽  
...  

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S351-S351
Author(s):  
Kevin J Downes ◽  
Anna Sharova ◽  
Marina Mitrou ◽  
Molly Hayes ◽  
Despoina Galetaki ◽  
...  

Abstract Background Ganciclovir (GCV) and valganciclovir (VGCV) are used for prophylaxis (PPX) and treatment for CMV in pediatric solid organ transplant (SOT) recipients, but the frequency and impact of toxicities from these medications are not well described. Methods Retrospective cohort study of children undergoing SOT at Children’s Hospital of Philadelphia from Jan 2012 - Jun 2018. EMR were reviewed to identify laboratory-based toxicities between 15 days and 1 year post-transplant; medication management within 14 days of toxicity onset was recorded. Toxicities were defined as GCV or VGCV-associated if a patient was on the antiviral at toxicity onset. We defined acute kidney injury (AKI) as ≥50% change in creatinine (Cr) from 30 days prior, leukopenia as WBC &lt; 3500/µL, neutropenia as ANC &lt; 1000/µL, and thrombocytopenia as &lt; 100K/µL. Incidence rates of toxicities on PPX and treatment were compared to rates during no antiviral using univariate Poisson regression. Results 285 children received 299 SOTs: 108 liver, 91 kidney, 69 heart, 31 lung. Nearly half (46%) of toxicities during the first year after transplant occurred while on GCV or VGCV PPX or treatment, but their use accounted for only 23% of all follow-up time. Receipt of VGCV and GCV PPX and treatment were associated with significantly higher incidence rates of toxicities compared to no antiviral (Fig 1). Of 259 GCV or VGCV-associated toxicities, 44% (n=113) were leukopenia, 26% (66) neutropenia, 26% (66) AKI, and 6% (15) thrombocytopenia (Table 1). Most recipients of VGCV PPX (64%) sustained at least one toxicity while on PPX. AKI during VGCV PPX led to stopping/dose-adjusting of VGCV in 43% and of immunosuppression in 57% of cases. Neutropenia during VGCV PPX resulted in stopping/dose-adjusting of VGCV in 63%, of immunosuppression in 36%, and of TMPX/SMX PPX in 36% of cases. During VGCV PPX, 81% of AKI was stage II/III (≥100% change in Cr) and 65% of neutropenia was severe (&lt; 500/µL); 11% of both AKI (n=6) and neutropenia (n=7) during VGCV PPX resulted in hospitalization. Figure 1. Incidence Rates of Toxicities from Day 15 through 1 Year After Transplant Table 1. Antiviral Use and Toxicity 2 Weeks to 1 Year After Transplant Conclusion GCV and VGCV use was associated with significant renal and hematological toxicities in pediatric SOT recipients. While VGCV and GCV are effective at preventing CMV disease in pediatric SOT, clinicians should consider risk of toxicity when evaluating CMV prevention strategies. Disclosures Kevin J. Downes, MD, Merck, Inc. (Grant/Research Support)


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