Cases Of Cytomegalovirus Disease Research Articles

Low-Dose Valganciclovir Prophylaxis Against Cytomegalovirus in Intermediate-Risk Liver and Dual-Abdominal Transplant Recipients.

Low-dose valganciclovir (VGC) for cytomegalovirus (CMV) prophylaxis post-transplant has been employed due to cost and safety. The incidence of CMV disease in CMV intermediate-risk liver recipients at 1-year after standard-dose prophylaxis is approximately 5%. However, there are limited data on outcomes after using a "true" low-dose VGC prophylaxis regimen in liver and dual-abdominal transplant recipients as VGC was not dose-adjusted in all patients with impaired renal function in prior studies. The objective was to assess the incidence of CMV associated with low-dose VGC prophylaxis in CMV intermediate-risk liver, simultaneous pancreas-kidney (SPK), and simultaneous liver-kidney (SLK) recipients with creatinine clearance (CrCl) >60 mL/min. This was a retrospective review of CMV intermediate-risk liver, SPK, and SLK recipients with CrCl >60 mL/min transplanted January 2018 to June 2022 who received VGC 450 mg daily for prophylaxis. The primary outcome was incidence of CMV infection 6-months post-transplant. Ninety-nine transplant recipients were included (79 liver, 11 SPK, 9 SLK). The primary outcome occurred in 13% of patients (liver 10%, SPK 36%, SLK 10%), including 1 case of CMV disease and 3 breakthrough infections. In addition, 6 patients experienced CMV infection between 6-months and 1-year. Recurrence occurred in 3 patients. There was no evidence of CMV resistance. Thirty patients experienced neutropenia within 1-year, 32 were prescribed granulocyte-colony stimulating factors, and 5 experienced thrombocytopenia. Two patients died due to graft-vs-host disease. Low-dose VGC prophylaxis led to comparable CMV infection rates at 6-months in CMV intermediate-risk liver and SLK recipients. However, as SPK recipients displayed higher rates of CMV infection, low-dose VGC should be avoided in this population.

CMV: 100 days after Kidney Transplantation

Cytomegalovirus (CMV) infection is frequent after kidney transplantation, typically occurring within the first 100 days post-transplant. This prospective, multicenter study aimed to estimate the frequency of CMV disease beyond 100 days post-transplant and demonstrate the usefulness of virological diagnosis during this period. Of 48 kidney transplant recipients with suspected CMV disease, 17% had positive CMV viremia, and 6% had confirmed CMV disease. The 3 cases of CMV disease presented with high viral loads, viral syndrome associated with tissue-invasive disease. For the 45 patients without confirmed disease, virological diagnosis allowed the identification of other etiologies, mainly infectious or iatrogenic. Although infrequent beyond 100 days, CMV disease can occur and be severe, justifying virological screening in the presence of suggestive signs. Differential diagnosis with other causes remains paramount.

Unrelated umbilical cord blood transplantation with low-dose anti-thymocyte globulin for children with severe aplastic anemia: A case series.

This study aimed to investigate the prognosis of unrelated umbilical cord blood transplantation (UCBT) using low-dose anti-thymocyte globulin (ATG) in children diagnosed with severe aplastic anemia (SAA). This retrospective case series study was conducted involving pediatric SAA patients treated at the Capital Institute of Pediatrics from January 2020 to February 2023. All patients underwent a reduced-intensity conditioning (RIC) regimen alongside low-dose ATG. The study comprised nine patients (five males) with a median age of 5 years (range: 1.7 to 7 years). The median follow-up duration was 799 days (range: 367 to 1481 days), during which all patients survived. The median time interval from diagnosis to transplantation was 3 months (range: 1 to 9 months). The median dosage of ATG administered was 5mg/kg (range: 2.5 to 7.5mg/kg). The median durations for granulocyte and platelet engraftment were 15 days (range: 12 to 23 days) and 26 days (range: 12 to 41 days), respectively. Three patients experienced grade 2-4 acute graft-versus-host disease (aGVHD). Epstein-Barr virus (EBV) reactivation was observed in three patients, while cytomegalovirus (CMV) reactivation occurred in seven patients, with no cases of CMV disease or post-transplant lymphoproliferative disorder (PTLD). One patient experienced recurrence 15 months after transplantation due to influenza A infection. These findings indicate that SAA patients may attain a favorable prognosis following UCBT with a RIC regimen combined with low-dose ATG.

Letermovir safety and efficacy for cytomegalovirus prophylaxis in adult Japanese kidney transplant recipients: a multicenter, open-label, noncomparative Phase 3 study

BackgroundLetermovir is approved for cytomegalovirus (CMV) prophylaxis in adult allogeneic hematopoietic cell transplantation recipients worldwide and is also approved in the United States for CMV prophylaxis in adult high-risk (D+/R−) kidney transplant recipients (KTRs). The safety and efficacy of letermovir for CMV prophylaxis in adult Japanese KTRs are reported here.MethodsIn this Phase 3, single-arm, open-label study, adult Japanese KTRs with CMV serostatuses D+/R−, D+/R+, and D−/R+ received letermovir 480 mg daily orally within 7 days post-transplant through Week 28. Participants were followed through Week 52. The primary objective was to evaluate letermovir safety and tolerability. Efficacy was a secondary objective, measured by CMV disease, CMV disease or infection requiring intervention, and quantifiable CMV DNAemia. All CMV disease cases were confirmed by an independent adjudication committee.ResultsAmong 22 participants (12 were D+/R−) who received letermovir prophylaxis, 20 (90.9%) experienced ≥ 1 AE through Week 28. Most AEs were mild to moderate in severity; no deaths were reported. During the prophylaxis period through Week 28, one transient case of quantifiable CMV DNAemia was detected, but no CMV disease or infection requiring intervention was reported. Through Week 52, four D+/R− participants met the endpoint of CMV disease or infection requiring intervention, of whom two had committee-confirmed CMV syndrome; all recovered with CMV therapy. A total of 5 participants had quantifiable CMV DNAemia through Week 52.ConclusionLetermovir was generally well tolerated, and the data support its use for the prevention of CMV disease/infection in adult Japanese KTRs.Trial registrationClinicalTrials.gov NCT04129398.

Abstract CT242: Phase 2b study of alloHSCT patients receiving RGI-2001, an NKT cell activator, demonstrates safety and protection from acute GVHD, correlating with increased NKT cell number in patient blood

Abstract Background: Allogeneic hematopoietic stem cell transplant (alloHSCT) has potentially curative outcomes for patients with certain hematologic malignancies but also has toxicity due to graft-versus-host-disease (GVHD), where donor-derived T cells attack the immune suppressed recipient, leading to significant mortality and morbidity. Natural killer T (NKT) and T-regulatory (Treg) cell levels in the donor product or in the recipient associate with protection from acute GVHD (aGVHD) and thus may represent therapeutic targets. RGI-2001 is a liposomal formulation of an NKT cell agonist, expanding both NKT and Tregs in animal models, resulting in prevention of aGVHD without compromising general immune function. Phase 1/2a studies of RGI-2001 demonstrated safety and potential efficacy in reducing aGVHD in alloHSCT using single doses. In this Phase 2b study, RGI-2001 was given weekly x 6 doses (100 ug/kg) in combination with standard GVHD prophylaxis. Results: RGI-2001 was given to 48 subjects undergoing matched (8/8) alloHSCT. Control data from the CIBMTR (n=207) was obtained and used as comparison. Patients receiving RGI-2001 did not have any serious infusion reactions, related serious adverse events, cases of cytomegalovirus disease, post-transplant lymphoproliferative disease, or graft failure. Compared to the CIBMTR group, the RGI-2001 group demonstrated lower grade II-IV aGVHD (day 180) and higher aGHVD-free survival (GFS) and overall survival. Relapse and cGVHD rates were similar between the groups. In addition, the number of NKT cells in the blood of the RGI-2001 group correlated with specific outcomes within this group. Grade II-IV at day 100 or d180 or GFS d180 occurred in >8 patients, and the mean NKT numbers at day 28 for these patients is lower than patients without occurrence. The number and percentages of Tregs, CD4+ T cells, CD8+ T cells, and NK cells did not correlate with any clinical endpoints. Conclusions: RGI-2001 given weekly x 6 doses is safe and well tolerated. Compared to matched cohort, the RGI-2001 cohort had decreased aGVHD and increased overall survival, suggesting that RGI-2001 could be added to alloHSCT regimens to reduce aGVHD while not affecting overall immune responses against infection and tumor relapse. Future studies will focus on optimizing dosage based on blood levels of NKT cells, elucidating the mechanisms of actions of RGI-2001, and identifying potential biomarkers of response. Citation Format: Jack D. Bui, Calvin Lee, Christine Caron, Dana Lee, Zachariah DeFilipp, Yi-Bin Chen. Phase 2b study of alloHSCT patients receiving RGI-2001, an NKT cell activator, demonstrates safety and protection from acute GVHD, correlating with increased NKT cell number in patient blood [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT242.

Cytomegalovirus Reactivations in Allogeneic Hematopoietic Stem Cell Transplantation from HLA-Matched and Haploidentical Donors with Post-Transplantation Cyclophosphamide

Cytomegalovirus (CMV) reactivations cause significant morbidity in allogeneic hematopoietic stem cell transplantation (HSCT) recipients. Graft-versus-host disease (GVHD) prophylaxis with post-transplantation cyclophosphamide (PTCy) is associated with an increased risk of CMV infections. Data are limited comparing HSCT with PTCy performed from matched sibling donors (MSDs), matched unrelated donors (MUDs), and haploidentical (Haplo) donors. In the present study, we aimed to characterize CMV reactivation and recurrence in patients with hematologic malignancies undergoing HSCT from MSD, MUD, and Haplo donors using PTCy as GVHD prophylaxis in the pre-letermovir era. We also analyzed risk factors of CMV reactivation, including GVHD as a time-dependent variable, on the incidence and mortality associated with CMV infections. We analyzed CMV reactivation in patients undergoing HSCT from 160 MSDs, 124 MUDs, and 82 Haplo donors from a single institution. Uniform GVHD prophylaxis with PTCy, sirolimus, and mycophenolate mofetil was given irrespective of donor type. Overall, 46% of patients had at least 1 CMV reactivation. The 1-year cumulative incidence of CMV infection was 39% for MSD, 44% for MUD, and 62% for Haplo donors (P < .001), with 96% of reactivations occurring before day +100. Multivariate analysis identified factors associated with the first CMV reactivation, including Haplo donor, positive recipient CMV serology, older patient age, and grade II-IV acute GVHD. The 1-year cumulative incidence of second reactivation from HSCT was 13%. Recipient CMV seropositivity, older patient age, and grade II-IV acute GVHD, but not type of donor, were identified as adverse factors for second CMV reactivation in multivariate analysis. The 1-year cumulative incidence of a third reactivation post HSCT was 4.4%. Ten cases of CMV disease were recorded, with no attributable deaths. Nevertheless, the risk for nonrelapse mortality was greater for patients who experienced CMV reactivation in multivariate time-dependent Cox model analysis. CMV reactivation is frequent in HSCT with PTCy in patients not receiving letermovir prophylaxis. Identified risk factors include the use of a Haplo donor, recipient CMV seropositivity, and grade II-IV acute GVHD. The prevalence of recurrent CMV reactivations is a noteworthy issue, especially after acute GVHD, warranting trials of secondary prophylaxis strategies.

Cytomegalovirus Reactivation in Postrenal Transplant Patients Immediately in Association with Coronavirus Disease 2019 (COVID-19) Infection: A Case Report of 2 Patients and a Brief Review of the Literature

Introduction: The coronavirus disease 2019 (COVID-19) infection has been associated with multiple opportunistic infections, including secondary cytomegalovirus (CMV) reactivation. Several cases of CMV syndrome and invasive CMV infection have been reported following severe COVID-19 infection worldwide during the COVID-19 pandemic in both immunocompetent and immunosuppressed patients. A case-control study conducted in India showed that during the first and second waves, CMV was the most common co-infection among fatal cases of severe COVID-19 lung infection in Indian renal transplant recipients. Case Presentation: We present 2 cases of CMV disease in postrenal transplant patients who developed clinical manifestations of CMV co-infection after mild COVID-19 infection during the fourth wave of COVID-19 infection in India. In both cases, CMV infection was treated by discontinuing mycophenolate mofetil and administering ganciclovir injections. However, the treatment resulted in 2 contrasting clinical outcomes: Cure and death. Conclusions: We reviewed the recent literature on the increased incidence of CMV reactivation after both COVID-19 infection and vaccination in immunocompetent and immunocompromised populations. Subsequently, we discussed some clinical questions relevant to the population of postrenal transplant recipients after the detection of mild COVID-19 infection.

P8.152: Clinical Characteristics and Factors Related to Recurrent Cytomegalovirus Infection Post-kidney Transplant in Adult Patients at Cho Ray Hospital

Introduction: Cytomegalovirus (CMV) is one of the main causes of opportunistic infections after kidney transplantation. Manifestations of CMV disease in post renal transplantation patients are quite discreet, non-specific and difficult to diagnose early. Asymptomatic recurrent CMV infection has been reported remarkably to increase mortality rate and rejection incidence, and effect on graft survival. The recently follow-up and treatment procedures’ changes make it urgent to re-evaluate the incidence and the factors related to the risk of CMV recurrence as well as the clinical characteristics of CMV infection in postkidney transplantation patients. This helps to control the recurrence of CMV infection as well as to diagnose CMV disease early and treat it promptly and appropriately to reduce the mortality rate of patients after transplantation. Method: Objective 1: Retrospective cohort study of adult renal transplant recipients between January 1, 2015 and December 31, 2018. Objective 2: A cross - sectional descriptive study on 22 cases of CMV disease in post kidney transplant patients to present a review of the main clinical aspects of cytomegalovirus infection in renal transplants with a focus on clinical approach and its future perspectives. Results: Objective 1: A total of 365 patients who received a renal transplant at Cho Ray hospital in the study time period were reviewed for the presence of CMV infection occurring less than 540 days after transplant. The recurrent CMV infection was observed in 254 cases (69,6%), but only 3 patients (0,8%) developed CMV disease. Independent risk factors of CMV infection were HLA >80 (HR = 2,309, 95% CI 1,021 – 4,071, p = 0,044), daily oral Prednisone doses used <0,5 mg/kg/day (HR = 0,178, 95% CI 0,084 – 0,374, p <0,001), Tacrolimus whole blood trough concentration ≤10 µg/L (HR = 0,445, 95% CI 0,243 – 0,816, p = 0,009), Cyclosporine wole blood trough concentration >150 µg/L (HR = 4,25, 95% CI 1,97 – 9,2, p < 0,001). Objective 2: Male majority (2/3), with average age of 47,5 ± 4,5. Rate of symptomic recurrence CMV infection in the first 6 months, 6 - 12 months, 1 - 5 years, 5 - 10 years after transplant were 45,4%, 9,1%, 27,3% and 18,2% respectively. Common clinical manifestations are fever 59,1%, respiratory, renal and gastrointestinal manifestations 31,8%, 27,3% and 13,6%, respectively. Two cases of CMV retinitis with typical fundus lesions were treated with intraocular Ganciclovir, however, vision was not fully recovered. Lymphopenia <1.000 cells/mm3 was observed in most cases of CMV disease after kidney transplantation. Quantitative PCR of CMV DNA in plasma ranged from 375 – 6.533.850 copies/mL. 6 of 22 cases of PCR CMV DNA in plasma >4.000 copies/mL, of which 5 severe cases developed rapidlly progressive respiratory failure and 2 deaths. Conclusion: Recurrent CMV infection has a high rate in adult patients after kidney transplantation, so it is necessary to take initiactive for screening, monitoring and treating early to reduce mortality and protect the transplanted kidney. The appropriate dose of immunosuppressants plays an important role in the prevention of recurrent CMV infection and the successful treatment of disease due to it. Key words: Cytomegalovirus, Kidney transplantation, Post-transplant infection. * Deparment of Tropical diseases– Cho Ray Hospital ** Nephrology Surgery – Cho Ray Hospital Coresponding author: Tho A. N. Vo, Deparment of Tropical diseases– Cho Ray Hospital. Email: [email protected]. Mobile: 0983888841.

The Role of Soluble Molecules CD25, CD38, and CD95 in the Development of Immunosuppression in Cytomegalovirus Infection

Introduction: Cytomegalovirus (CMV) infection is a common beta-herpesvirus infection widely spread in the human population. The proportion of infected population increases with age and approaches 100 % in elderly people. The infection is usually latent but is capable of reactivation when immunosuppression develops. The mechanisms of reactivation are not fully understood. The objective of our study was to evaluate the role of soluble molecules CD25, CD38, CD95 in the development of immunosuppression in CMV infection. Materials and methods: We used 18 serum samples from cases of CMV disease in the stage of reactivation, all confirmed by clinical and laboratory data. The patients received treatment in Nizhny Novgorod Infectious Disease Hospital No. 2. The serum content of the total and oligomeric soluble molecules CD25, CD38, and CD95 was identified by ELISA using monoclonal and polyclonal antibodies against human peripheral blood mononuclear cell proteins. The results were recorded spectrophotometrically and evaluated by converting optical density units to conventional units (U/mL). Results: We established an increase in the serum content of total and oligomeric fractions of soluble molecules CD25, CD38, and CD95 in the cases of CMV disease. While the serum content of the total and oligomeric fractions of molecules CD25 and CD38 increased equally, the oligomeric fraction of molecules СD95 demonstrated a more pronounced increase compared to the total fraction of these molecules. Our findings suggest the immune response suppression mechanism associated with initiation of apoptosis of effector T lymphocytes involving oligomeric form of molecules CD95. Conclusion: Changes in the content, structural and functional state of soluble differentiating molecules CD25, CD38, and CD95 indicate their involvement in immunosuppression mechanisms in patients with CMV infection.

Incidence, features, and outcomes of cytomegalovirus DNAemia in unmanipulated haploidentical allogeneic hematopoietic stem cell transplantation with post-transplantation cyclophosphamide.

Conflicting data have been published as to the risk of cytomegalovirus (CMV) DNAemia and CMV disease in patients undergoing haploidentical hematopoietic stem cell transplantation (haplo-HSCT) with post-transplantation cyclophosphamide. We conducted a multicenter retrospective study including 118 patients subjected to unmanipulated haplo-HSCT to further clarify this issue. An historic cohort comprising 165 patients undergoing other transplant modalities (HLA-matched related, matched unrelated or mismatched) was built for comparison purposes. Plasma CMV DNA monitoring was performed using two highly sensitive real-time PCR assays. Overall, the cumulative incidence of CMV DNAemia, recurrent CMV DNAemia, and CMV DNAemia requiring preemptive antiviral therapy in patients undergoing haplo-HSCT was 63.9%, 34.9%, and 50.1%, respectively. These figures were rather comparable for other transplant modalities (P=.22, P=.13 and P=.72, respectively). A trend toward longer duration of episodes and shorter CMV DNA doubling times was observed in haplo-HSCT patients in comparison with other transplant modalities. Furthermore, median CMV DNA peak load was significantly higher in haplo-HSCTs (P=.008), yet overall mortality by day 180 and 365 was the same across comparison groups. There were five cases of CMV disease, and all occurred in haplo-HSCT patients. This latter observation is worrying and merits further investigation. The incidence of initial and recurrent episodes of CMV DNAemia either requiring or not antiviral therapy in unmanipulated haplo-HSCT was comparable to other transplant modalities in our cohort.

Probable Donor-Derived Cytomegalovirus Disease After Keratolimbal Allograft Transplantation

To report a case of probable donor-derived cytomegalovirus (CMV) infection after keratolimbal allograft (KLAL) transplantation. Observational case report. A 41-year-old man with a history of aniridic keratopathy and limbal stem cell deficiency underwent KLAL in his right eye. Preoperatively, he was negative for CMV IgG and IgM. Postoperatively, he was maintained on tacrolimus and mycophenolate mofetil for systemic immunosuppression; he was also on prophylactic valganciclovir (for CMV) and trimethoprim/sulfamethoxazole (for pneumocystis pneumonia) for 1 month. Approximately 5 weeks postoperatively, he developed a nonproductive cough, rhinorrhea, and dyspnea. His condition did not improve with oral azithromycin or levofloxacin. He developed worsening symptoms over the next 2 weeks despite therapy. The serum CMV polymerase chain reaction was positive, and he was readministered valganciclovir with subsequent resolution of symptoms. We present the first case of CMV disease in a seronegative patient who received a presumed CMV-seropositive donor KLAL. Similar to solid organ transplantation, prophylactic and therapeutic management of CMV infection is necessary in the setting of systemic immunosuppression.

Risk factors for cytomegalovirus disease in seropositive renal transplant recipients; a single-center case-controlled study

Background: Risk factors for cytomegalovirus (CMV) disease in renal transplant recipients have been evaluated in industrialized countries with relatively low CMV seroprevalence. Objectives: We aimed to determine which factors are related to this illness in a high CMV seroprevalence country. Patients and Methods: A case-control study was performed with data from a 5-year follow-up of 260 kidney transplant recipients at our center. Odds ratios were calculated using the Mantel-Haenszel method. Results: A total of 25 cases of CMV disease occurred during the study period. Recipient age greater than 55 years old (odds ratio: 4.95, 95% CI: 1.44–17.0) and use of thymoglobulin (odds ratio: 4.84; 95% CI: 1.10–21.39) were the only independent predictors for CMV disease. There was not any relationship between the previous serologic status of both donor and receptor and the occurrence of CMV disease. We did not observe any association between the immunosuppressive regimens and CMV disease, except for thymoglobulin. Conclusions: Only recipient age and thymoglobulin administration were related to CMV disease. Further studies are needed to determine if prophylactic treatment confers clinical benefit in this subset of patients.

Acute Pancreatitis in Patients Living with HIV

Background: Acute pancreatitis in HIV positive patients remains a management challenge even with a Highly Active Antiretroviral Therapy (HAART) era. Objective: Report the prevalence, clinical and radiological features of acute pancreatitis associated with HIV. Patients and methods: Retrospective study conducted from January 1999 to June 2015 in HIV positive patients admitted with acute pancreatitis in the Infectious Disease Unit, Ibn Rochd, Casablanca. The Balthazar Grade score was used to assess radiological severity of the disease. Results: During this period, 39 patients had an acute pancreatitis or an incidence of 0.6/1000 inhabitant/year. The mean age was 33.72 years (range: 18 to 48 years), mostly represented by females (68% to 32% male).The known risk factors included an alcohol abuse in 15 patients (52%), a history of pancreatitis in two patients (5%), cholecystitis in four patients (14%), and intravenous drug abuse in two patients (5%). Nineteen patients (65%) were on HAART regimen and only nine patients (31%) were receiving cotrimoxazole as prophylaxis. Twenty-two patients (76%) were in stage C of CDC. Twenty-one (72%) patients had a mean CD4 count below 200/mm³ and a HIV viral load above 1000 copies/ml in seventy nineteen (65%) patients. Pancreatitis was symptomatic in all cases. The median amylasemia level was 120 IU/L, serum lipase 672.7 IU/L and 1,23 mg/dl triglycerides. All patients had an abnormal pancreas CT scan of which twelve (41%) patients were in stage A of AP. The main causes found were drug toxicity of which 6 cases were due to stavudine, meglumine antimony in 3 cases, didanosine in 1 case, anti-tuberculous treatment in 1 case and opportunistic infections of which 4 cases were tuberculosis, 4 cases of cytomegalovirus disease and cryptosporidiosis in 2 cases respectively. The main complications were: shock in 9 cases, 2 cases of diabetes and pancreatic pseudocysts in 2 cases. The evolution was fatal in 45% of cases. The median duration for hospital course was 10 days (range 6-50 days). Conclusion: Acute pancreatitis is a serious condition in HIV-positive patients. Drug toxicity and opportunistic infections represented the most frequent causes.

Cytomegalovirus prevention strategies in seropositive kidney transplant recipients: an insight into current clinical practice.

There is notable heterogeneity in the implementation of cytomegalovirus (CMV) prevention practices among CMV-seropositive (R+) kidney transplant (KT) recipients. In this prospective observational study, we included 387 CMV R+ KT recipients from 25 Spanish centers. Prevention strategies (antiviral prophylaxis or preemptive therapy) were applied according to institutional protocols at each site. The impact on the 12-month incidence of CMV disease was assessed by Cox regression. Asymptomatic CMV infection, acute rejection, graft function, non-CMV infection, graft loss, and all-cause mortality were also analyzed (secondary outcomes). Models were adjusted for a propensity score (PS) analysis for receiving antiviral prophylaxis. Overall, 190 patients (49.1%) received preemptive therapy, 185 (47.8%) antiviral prophylaxis, and 12 (3.1%) no specific intervention. Twelve-month cumulative incidences of CMV disease and asymptomatic infection were 3.6% and 39.3%, respectively. Patients on prophylaxis had lower incidence of CMV disease [PS-adjusted HR (aHR): 0.10; 95% confidence interval (CI): 0.01-0.79] and asymptomatic infection (aHR: 0.46; 95% CI: 0.29-0.72) than those managed preemptively, with no significant differences according to the duration of prophylaxis. All cases of CMV disease in the prophylaxis group occurred after prophylaxis discontinuation. There were no differences in any of the secondary outcomes. In conclusion, antiviral prophylaxis was associated with a lower occurrence of CMV disease in CMV R+ KT recipients, although such benefit should be balanced with the risk of late-onset disease.

The Role of Secondary Cytomegalovirus Prophylaxis for Kidney and Liver Transplant Recipients

The role of secondary cytomegalovirus (CMV) prophylaxis, defined as the continuation of valganciclovir to prevent relapse after the successful treatment of CMV disease, is not well understood. Cases of CMV disease in patients who underwent kidney or liver transplantation from January 2001 to January 2010 were reviewed to determine if the use of secondary prophylaxis was associated with fewer relapses or other favorable outcomes. Secondary prophylaxis was used at the discretion of each treating clinician, without an institutional protocol. Twenty-two cases of CMV disease in kidney transplant recipients and 20 cases in liver transplant recipients were included. Relapsed CMV disease was significantly more common among kidney transplant recipients (5/22 vs. 0/20, P = 0.049). Of 22 kidney transplant recipients, 16 received secondary prophylaxis. After a mean of 3.7 years, relapsed CMV disease occurred in three of 16 patients who received secondary prophylaxis and in two of six who did not. Among liver transplant recipients, only two of 20 patients received secondary prophylaxis. After a mean of 3.2 years, no relapsed CMV disease occurred. The use of secondary prophylaxis was not significantly associated with fewer episodes of CMV relapse, graft loss, or death. Time to clearance of CMV viremia during treatment was significantly longer in those who relapsed (mean, 30 days vs. 20 days; P = 0.037). These findings suggest that secondary CMV prophylaxis may not provide additional benefit after the successful treatment of CMV disease, particularly among liver transplant recipients.

Pre-emptive Therapy for the Cytomegalovirus Infection After Liver Transplantation in Endemic Areas and Its Optimal Diagnostic Method

BackgroundThe incidence of positive cytomegalovirus (CMV) IgG tests among Asian populations is high. Both universal prophylaxis and pre-emptive therapy (PT) have been recommended for the moderate-risk group (D+/R+), whose incidence of CMV infection has been reported variously, and for whom the optimal diagnostic method has not been firmly established. Herein, we sought to analyze our experience with CMV infections using PT and to discuss the optimal diagnostic method. MethodsWe retrospectively, analyzed 32 consecutive liver transplant recipients between December 2009 and April 2012 for clinicopathologic data including mortality and rejection rates, comparing 2 diagnostic tools for CMV: pp65 antigen assay and real-time reverse-transcriptase polymerase chain reaction (RT-PCR). ResultsTwenty-one patients (65.6%) were positive for the CMV antigen assay, and 13 (40.6%) had positive RT-PCR results. There were no cases of CMV disease during the follow-up and no difference in rejection (P = .529) or mortality (P = .471) rates with regard to PCR positivity. The mean diagnosis time was 26.5 days postoperative. Among the patients who exhibited negative RT-PCR results, 7 (41.18%) were positive on the pp65 antigen assay. ConclusionCMV infection rates were higher when compared to same-risk population from Western countries. As a diagnostic tool for CMV infection, screening with the pp65 antigen assay and confirmation with real-time RT-PCR seemed to provide an optimal diagnostic tool.

Cytomegalovirus esophagitis presents as chest pain in a renal transplant recipient

Cytomegalovirus esophagitis presents as chest pain in a renal transplant recipient

Cytomegalovirus disease and infection in lung transplant recipients in the setting of planned indefinite valganciclovir prophylaxis

The optimal method of both predicting and preventing cytomegalovirus (CMV) disease in lung transplant recipients remains unclear. In particular, the most appropriate duration of CMV prophylaxis post transplant is unresolved. We report herein our experience with a planned indefinite regimen of valganciclovir prophylaxis and monitoring of quantitative CMV load in bronchoalveolar lavage (BAL) fluid. We performed a single-center observational study with both prospective and retrospective components. The included patients (n = 128) received a planned regimen of indefinite valganciclovir prophylaxis post transplant, regardless of donor (D)/recipient (R) CMV serostatus. Real-time polymerase chain reaction assay for detection of CMV in BAL was prospectively performed over a 1-year period. Clinical data were reviewed retrospectively; median follow-up was 24.8 months (range 1-93 months). Sixty-five patients (50.6%) discontinued valganciclovir prophylaxis, either temporarily or permanently, with a primary cause of mild leukopenia. Six cases of CMV disease were identified (4.7%), with no significant difference between those who were on continuous prophylaxis or not (4.6% vs. 4.9%; P = non-significant [ns]). However, those who discontinued prophylaxis showed an increased incidence of laboratory-detected CMV infection (40.7% vs. 12.7%; P = 0.001). High-risk D+/R- patients did not demonstrate a significantly increased incidence of CMV disease (8.1% vs. 3.3% other serotypes; P = ns). Three patients (2.3%) developed valganciclovir-resistant CMV disease. Molecular detection of CMV in BAL fluid was significantly more sensitive than shell vial culture. However, BAL CMV viral load was not predictive of subsequent disease development. Extended valganciclovir prophylaxis for all lung transplant recipients led to a low incidence of CMV disease and resistance. In such low-incidence populations, routine quantitation of CMV in BAL did not confer significant clinical benefit over non-quantitative methods in prediction of CMV disease onset.

Impact of Cytomegalovirus Disease in D+/R– Kidney Transplant Patients Receiving 6 Months Low-Dose Valganciclovir Prophylaxis

Late-onset cytomegalovirus (CMV) disease remains common in CMV serology naïve kidney transplant patients of CMV serology positive organs (D+/R-) despite the use of antiviral prophylaxis. We studied clinical efficacy of 6-month low-dose valganciclovir (VGCV) prophylaxis, risk factors for late-onset CMV disease and its impact on kidney transplant outcomes. Between October 2005 and December 2009, 166 consecutive D+/R- kidney alone and simultaneous pancreas and kidney transplant patients received VGCV 450 mg daily for 6 months after transplantation. After a median follow-up of 3.2 years, 30 cases of CMV disease occurred within the first 2 years after transplantation with a cumulative incidence of 11.5 and 18.1% at 1 and 2 years, respectively. The use of an induction agent with rabbit antithymocyte globulin and older donor age were factors associated with the risk of late-onset CMV disease (AHR 2.91, 95% CI 1.18-7.20, p = 0.021 and AHR 1.03, 95% CI 1.01-1.06, p = 0.016, respectively). Late-onset CMV disease was associated with increased risk for death-uncensored graft loss (AHR 2.95, 95% CI 1.15-7.61, p = 0.025). In conclusion, late-onset CMV disease continues to negatively impact kidney transplant outcome despite 6-month low-dose VGCV prophylaxis. Investigations focusing on novel preventive approaches should be emphasized.

Cytomegalovirus Viremia, Pneumonitis, and Tocilizumab Therapy

Cytomegalovirus Viremia, Pneumonitis, and Tocilizumab Therapy