Positive Cytomegalovirus Antigenemia Research Articles

Human Cytomegalovirus Is Associated with Lower HCC Recurrence in Liver Transplant Patients.

Human cytomegalovirus (CMV) infection has been reported to compromise liver transplantation (LT) outcomes. Recent studies have shown that CMV has a beneficial oncolytic ability. The aim of this study was to investigate the impact of CMV on tumor recurrence in patients with hepatocellular carcinoma (HCC) who underwent liver transplantation (LT). This retrospective study enrolled 280 HCC patients with LT at our institute between January 2005 and January 2016. Their relevant demographic characteristics, pre- and post-LT conditions, and explant histology were collected. A CMV pp65 antigenemia assay was performed weekly following LT to identify CMV infection. A total of 121 patients (43.2%) were CMV antigenemia-positive and 159 patients (56.8%) were negative. A significantly superior five-year recurrence-free survival was observed among CMV antigenemia-positive patients compared with the CMV-negative group (89.2% vs. 79.9%, p = 0.049). There was no significant difference in overall survival between the positive and negative CMV antigenemia groups (70.2% vs. 75.3%, p = 0.255). The major cause of death was HCC recurrence in CMV antigenemia-negative patients (51.3%), whereas more CMV antigenemia-positive patients died due to other bacterial or fungal infections (58.3%). In the multivariate analysis, the independent risk factors for tumor recurrence included positive CMV antigenemia (p = 0.042; odds ratio (OR) = 0.44; 95% confidence interval (CI) = 0.20–0.97), microscopic vascular invasion (p = 0.001; OR = 3.86; 95% confidence interval (CI) = 1.78–8.36), and tumor status beyond the Milan criteria (p = 0.001; OR = 3.69; 95% CI = 1.77–7.71). In conclusion, in addition to the well-known Milan criteria, human CMV is associated with a lower HCC recurrence rate after LT. However, this tumor suppressive property does not lead to prolonged overall survival, especially in severely immunocompromised patients who are vulnerable to other infections.

Valganciclovir prophylaxis for cytomegalovirus infection in pediatric kidney transplant recipients: a single-center experience.

There are two approaches for treating cytomegalovirus (CMV) infection occurring after kidney transplantation (KTx). One is preemptive therapy in which treatment is started after confirming positive CMV antigenemia using periodic antigenemia assay. The other approach is prophylactic therapy in which oral valganciclovir (VGCV) is started within 10days after KTx and continued for 200days. The Transplantation Society guidelines recommend prophylactic therapy for high-risk (donor's CMV-IgG antibody positive and recipient's negative) pediatric recipients. However, the adequate dose and side effects of VGCV are not clear in children, and there is no sufficient information about prophylaxis for Japanese pediatric recipients. A single-center retrospective analysis was conducted on case series of high-risk pediatric patients who underwent KTx and received oral VGCV prophylaxis at the Department of Pediatric Nephrology, Tokyo Women's Medical University, between August 2018 and March 2019. Data were collected using medical records. The dose of administration was 450mg in all the study patients (n = 5). Reduction or discontinuation was required in four of five patients due to adverse events, which included neutropenia in one patient, anemia in two patients, and neutropenia and digestive symptoms in one patient. Late-onset CMV disease occurred in all patients. No seroconversion was observed during prophylaxis. Our preliminary study suggests that the dosage endorsed by The Transplantation Society may be an overdose for Japanese pediatric recipients. Further studies are required to examine the safety and efficacy of VGCV prophylaxis in Japanese pediatric recipients.

SAT-342 CYTOMEGALOVIRUS INFECTION IN KIDNEY TRANSPLANTS RECIPIENTS: EXPERIENCE OF A SINGLE CENTER

Cytomegalovirus (CMV) is the most common infection after organ transplantation; it can be a major cause of morbidity, mortality. Optimal prevention, diagnosis, and treatment of active CMV infection enhance transplant outcomes. But, the management of CMV varies considerably among transplant centers. We described the incidence, clinical profile, outcome, and risk factors for the development of CMV infection among renal transplant recipients. We studied kidney transplants recipients admitted for CMV infection from January 1998 to September 2018. CMV infection was present if the patient had positive CMV antigenemia or positive PCR CMV. CMV disease was diagnosed if clinical signs and symptoms are associated with CMV infection. About 48 cases of CMV infection was confirmed in our study. The majority of patients were CMV seropositive recipients from seropositive donors (88,8%). Only 29, 16% of our patients had symptomatic CMV infection and 70, 8% had CMV disease. 52, 1% of our recipients developed CMV infection 2 months post-transplantation. Fever was the most common presenting symptoms (97, 2%) and the most common biological disorder were leukopenia (83,3%). Among the 6 who developed tissue-invasive CMV (13,3%), 3 had CMV pneumonitis, 1 has two recurrent episodes of CMV uveitis for, 1 had colitis, and 1 had macrophage activation syndrome induced by CMV during pregnancy. Risk factors that were statistically significant in the development of CMV disease were as follows: recent rejection treatment (p= 0,021) and HLA mismatch (p=0, 05). For the indirect effect of CMV infection, the most frequent was bacterial and fungal coinfections (33, 35%), then we found, graft dysfunction (25%), acute graft rejection (14, 5%), new-onset post-transplant diabetes (6, 25%), post lymphoproliferative disease (1 case, 2, 2%), and mortality incidence was 20%. The cardiovascular events were significantly associated with CMV infection (p=0.02). We also demonstrate a significant association between CMV infection and long term graft function expressed either as graft dysfunction or graft loss: The DFG was lower in CMV infection group in 6 months, 1 year, 2 years and 10 years. The graft loss was significantly superior in patients with CMV infection/disease than patients without CMV (p= 0,05). CMV infection and CMV disease remain an infectious cause of significant clinical problems, morbidity, and mortality. Despite the absence of prophylaxis, the complications associated with CMV infection are usually not higher than in other countries. However, the use of universal prophylaxis and preemptive therapy remains necessary to reduce the hospitalization rate and consequence of CMV infection.

RISK FACTORS FOR POST-LIVER TRANSPLANT BILIARY COMPLICATIONS IN THE ABSENCE OF ARTERIAL COMPLICATIONS

ABSTRACT Background - Biliary complications (BC) represent the most frequent complication after liver transplantation, up to 34% of cases. Aim: To identify modifiable risk factors to biliary complications after liver transplantation, essential to decrease morbidity. Method: Clinical data, anatomical characteristics of recipient and donors, and transplant operation features of 306 transplants with full arterial patency were collected to identify risk factors associated with BC. Results: BC occurred in 22.9% after 126 days (median) post-transplantation. In univariate analyses group 1 (without BC, n=236) and group 2 patients (with BC, n=70) did not differ on their general characteristics. BC were related to recipient age under 40y (p=0.029), CMV infection (p=0.021), biliary disease as transplant indication (p=0.018), lower pre-transplant INR (p=0.009), and bile duct diameter <3 mm (p=0.033). CMV infections occurred sooner in patients with postoperative biliary complications vs. control (p=0.07). In a multivariate analysis, only CMV infection, lower INR, and shorter bile duct diameter correlated with BC. Positive CMV antigenemia correlated with biliary complications, even when titers lied below the treatment threshold. Conclusions: Biliary complications after liver transplantation correlated with low recipient INR before operation, bile duct diameter <3 mm, and positive antigenemia for CMV or disease manifestation. As the only modifiable risk factor, routine preemptive CMV inhibition is suggested to diminish biliary morbidity after liver transplant.

Incidence of Cytomegalovirus Antigenemia in patients with autoimmune rheumatic diseases: a 3-year retrospective study

ObjectiveTo determine the incidence of positive CMV antigenemia (CMV-Ag) in patients with autoimmune rheumatic diseases (AIRD) and to describe the outcomes of these patients.MethodsFrom January 2011 to December 2014, a total of 443 patients with AIRD were enrolled in this retrospective analysis. Demographic, clinical and laboratory data, current clinical manifestations, organs affected by CMV infection, therapeutic management and outcomes were evaluated. The CMV-Ag was considered positive when one cell was detected at least.ResultsCMV-Ag was requested in 70 (15.8%) patients with suspicious CMV infection and was positive in 24 (34.3%). The incidence rate of positive CMV-Ag was 4.97% (95% CI 3.1–7.4%). Systemic lupus erythematosus (SLE) (59%), followed by ANCA-related vasculitis (18.2%) and rheumatoid arthritis (9%) were the diseases more associated with positive CMV-Ag. At the time of CMV infection, SLE patients had moderate to severe disease activity, with high frequency of positive anti-dsDNA antibody (69.2%) and complement consumption (61.5%), as well as high doses of corticosteroids and use of immunosuppressants. The main CMV sites involved were lung (45.5%), bone marrow (40.9%) and gut (27.3%). Mortality rate was 45.5%, especially in those with higher doses of daily oral corticosteroids (107 ± 55.4 mg vs. 71.7 ± 46.3 mg; p = 0.07) and lower number of lymphocytes (309 ± 368.2/mm3 vs. 821 ± 692.9/mm3; p = 0.06).ConclusionsOur data showed high incidence of CMV-Ag in AIRD patients, particularly those with SLE and greater disease severity. In addition, it was observed high mortality in these patients, highlighting the CMV infection should be included in differential diagnosis.

1-Year Coronary IVUS in Heart Transplant Recipient Fails to Predict 10-Year Cardiovascular Mortality

Purpose Cardiac Allograft Vasculopathy (CAV) is one of the most frequent long-term causes of death after heart transplant (HTx). Immunological and non-immunological factors are implicated in its development. IVUS is the gold standard for CAV diagnosis. Our study evaluates the correlation between the intimal index (IntIndx=[(intimal area/vessel area)*100]) evaluated with IVUS at 1-year after HTx (as a marker of CAV), the presumed pathogenetic factors for early CAV and 10-year cardiovascular (CV) mortality. Methods From January 2008 and June 2009, 28 patients (Pts) underwent IVUS at one-year follow-up after HTx (Female 32,1%, mean age 49,3±10,6 ). According to literature, we used a 40% Intindx cut-off to identify CAV. Study sample was divided into two groups: group A (GA: IntIndx Results Overall 10-year mortality was 21.4% (6 PTs), while 10-year CV mortality was 7.1% (2 Pts, 1 Pts died for heart failure due to advanced CAV, while 1 Pts underwent re-transplant due to end-stage CAV). LAD IntIndx ≥40% was significantly associated with serum HDL at 1-month post-HTx (GA 61.6±12.7 vs GB 49.2±11.3 mg/dl; p 0.012), 1-year post-HTx serum Triglycerides (GA 134.4±29.3 vs GB 179.9±65.9 mg/dl; p 0.041), the percentage of Pts with serum ciclosporine (CyA) in therapeutic range 2 hours after ingestion (GA 91.9%±8% vs GB 78.8±18%; p 0.034), donor age (GA 38.3±12.7 vs 47.4±8.8 year; p 0.003), and donated heart ischemic time (GA 178.6±41.6 vs GB 150.7±29.1 min; p 0.046). Serum HDL at 1-, 6- and 12-months post-HTx, donor age, early positive CMV antigenemia (pp65>50 cells), were also statistically significant risk-facotrs for CAV at 1-year. Conclusion The low even-rate did not allow to compare 10-year CV mortality with IVUS findings, however, despite the small number of patients, our study shows a correlation between IVUS intimal thickness and various risk factors potentially implicated in CAV development and pathogenesi (donor age, CMV infections, non-adequate immune-suppression, and lipid profile after HTx). Further analysis on 1-year IVUS findings and non fatal CAV event are mandatory to better understand IVUS role in heart transplant recipient.

Characteristics of cytomegalovirus enterocolitis in patients with or without inflammatory bowel diseases

Objectives: Cytomegalovirus (CMV) disease is more common in immunocompromised patients but may occur in people with normal immune function. In addition, CMV enterocolitis can aggravate inflammatory bowel diseases (IBD), but there was little knowledge of differences in clinical and endoscopic features of CMV enterocolitis between patients with IBD and without IBD. The aim of this study was to determine the difference in clinical implication in CMV enterocolitis between the IBD patients and non-IBD patients.Methods: This was a retrospective study of 82 patients with CMV enterocolitis based on the pathologic findings at two tertiary referral hospitals from 2003 to 2013. Clinical and endoscopic characteristics and clinical course were analyzed according to the presence of IBD.Results: Of the 82 patients, 25 (30.5%) had IBD and 57 (69.5%) did not have IBD. Hematochezia was more common in IBD patients (84.0% vs. 35.1%; p = .001), but fever and positive CMV antigenemia were more common in non-IBD patients (50.9% vs. 12.0%; p = .001; 54.4% vs. 28.0; p = .027). Endoscopic findings showed more ulcer with inflammation in IBD patients (68.0% vs. 35.2%; p = .005). Sixty-four patients were treated with antiviral agents and 12 patients who did not receive antiviral agents recovered spontaneously. All naturally healed patients were in normal immune status.Conclusions: Hematochezia is more common in IBD patients and fever/CMV antigenemia is more common in patients without IBD. In patients without IBD, the natural resolution of CMV enterocolitis is expected at least in normal immune function.

Half-dose ganciclovir preemptive treatment of cytomegalovirus infection after pediatric allogeneic hematopoietic stem cell transplantation.

Ganciclovir (GCV) has been widely used as preemptive therapy after hematopoietic stem cell transplantation (HSCT), although bone marrow suppression is a known accompaniment, with secondary infection or bleeding as potential complications. Our aim was to evaluate clinical outcomes in pediatric patients with low cytomegalovirus (CMV) antigenemia levels using half the dosage of GCV generally given preemptively. Patients received half doses of intravenous GCV (5 mg/kg once daily, 6 days/week) at CMV antigenemia levels <10/200,000 cells. At higher levels of CMV antigenemia, conventional doses of GCV (5 mg/kg every 12 h) were administered. A total of 130 patients were evaluated, detecting CMV antigenemia in 87 (66.9%). Of these patients, 74 (85.1%) were treated preemptively with half-dose GCV, which proved effective as sole therapy in 51 (68.9%). CMV retinitis developed in 4 patients, 2 of whom initially were given half-dose GCV. All infections resolved successfully, with no CMV-related deaths. CMV seropositivity in recipients was the only significant risk factor for positive CMV antigenemia (hazard ratio [HR] = 10.05, P = 0.046). Compared with half-dose GCV administration, conventional GCV dosing resulted in a higher rate of severe neutropenia, defined as absolute neutrophil count <0.5 × 10(9) /L (HR = 4.30, P = 0.015). Half-dose GCV therapy at CMV antigenemia levels <10/200,000 cells is an effective and safe means of preemptively treating pediatric CMV infection after HSCT.

Cytomegalovirus Reactivation in Adult Recipients of Autologous Stem Cell Transplantation: a Single Center Experience.

IntroductionCytomegalovirus (CMV) reactivation and infection are well-recognized complications after allogeneic stem cell transplantation (SCT). Only a few studies have addressed CMV reactivation after autologous SCT (ASCT).MethodsWe retrospectively reviewed medical records of 210 adult patients who underwent ASCT for lymphoma or multiple myeloma (MM) at a single center from January 1st, 2007 until December 31st, 2012. All patients were monitored weekly with CMV antigenemia test till day 42 after transplantation, and for 2 months after last positive test in those who had any positive CMV antigenemia test before day 42.ResultsThirty-seven (17.6%) patients had CMV reactivation; 23 patients had lymphoma while 14 had MM as the underlying disease. There was no difference in the rate of CMV reactivation between lymphoma and MM patients (20% versus 14.7%, P = 0.32). The majority of the patients were treated with ganciclovir/valganciclovir, all patients had their reactivation resolved with therapy, and none developed symptomatic CMV infection. None of the patients who died within 100 days of transplantation had CMV reactivation. Log-rank test showed that CMV reactivation had no effect on the overall survival of patients (P values, 0.29).ConclusionIn our cohort, CMV reactivation rate after ASCT was 17.6%. There was no difference in reactivation rates between lymphoma and MM patients. With the use of preemptive therapy, symptomatic CMV infection was not documented in any patient in our cohort. CMV reactivation had no impact on patients’ survival post ASCT.

Usefulness of the cytomegalovirus antigenemia assay in patients with ulcerative colitis.

Background/AimsPatients with ulcerative colitis (UC) are at high risk for cytomegalovirus (CMV) reactivation. The usefulness of the CMV antigenemia assay in active UC patients has rarely been studied. We assessed whether the assay detects CMV colitis and predicts clinical outcomes in patients with UC.MethodsWe retrospectively reviewed the medical records of patients hospitalized for moderate-to-severe UC from 2003 to 2012. Positive CMV antigenemia was defined as ≥1 pp65-positive cell per 2×105 polymorphonuclear neutrophils. CMV colitis was defined as the presence of inclusion bodies and/or positive immunohistochemistry in the colonic mucosa. The primary outcome was steroid refractoriness, defined as the absence of clinical improvement after intravenous high-dose steroid administration.ResultsA total of 43 patients were enrolled. CMV antigenemia was detected in 12 (27.9%) patients. Positive CMV antigenemia was significantly associated with CMV colitis (P =0.001). The sensitivity and specificity of positive CMV antigenemia for diagnosing CMV colitis were 66.7% and 87.1%, respectively. Steroid refractoriness was found in 11 of 12 (91.7%) and 12 of 31 (38.7%) patients with positive and negative CMV antigenemia, respectively (P =0.002). The independent predictors for steroid refractoriness were positive CMV antigenemia (adjusted odds ratio [OR], 7.73; 95% confidence interval [CI], 1.22-49.19; P =0.030) and a shorter duration from the diagnosis of UC (adjusted OR, 0.99; 95% CI, 0.98-0.99; P =0.025).ConclusionsThe CMV antigenemia assay shows low sensitivity but high specificity for detecting CMV colitis and may predict steroid-refractory UC. Early rescue therapy might be considered in UC patients positive for CMV antigenemia.

Comparison between valganciclovir and aciclovir/valaciclovir for CMV prophylaxis in pediatric renal transplantation.

Prophylaxis has dramatically decreased the occurrence of cytomegalovirus (CMV) infection after renal transplantation. Optimal regimens of treatment remain controversial, especially in pediatric recipients. The aim of this study was to evaluate the effectiveness of valganciclovir (VGC) versus aciclovir/valaciclovir (ACV) in a pediatric renal transplant population. Data from 101 renal transplantations were retrospectively analyzed. Except those with R-/Dstatus, all patients received prophylaxis either with ACV, n = 39 or VGC, n = 38. Incidences of positive CMV antigenemia and disease, as well as the delay in relation to the prophylaxis, were collected during at least 12 months after the end of treatment. Positive CMV antigenemia was reported in 34 patients (ACV: 16, VGC: 16, no prophylaxis: 2). CMV disease occurred in 15 patients (ACV: 5; VGC: 8) (ns). For the majority of patients under VGC, positive CMV antigenemia occurred within the year following the withdrawal of prophylaxis (VGC: 14; ACV: 5, P <0.05), whereas it occurred during prophylaxis in 11 patients under ACV versus two under VGC (P <0.05). The over-all incidence of positive CMV antigenemia was similar between ACV and VGC prophylaxis. However, VGC was more efficient to prevent early CMV infection while patients treated with ACV had less CMV infection or disease after the end of the prophylaxis.

When is an Assay of Cytomegalovirus Antigenemia Useful in Detecting Cytomegalovirus Colitis?

Cytomegalovirus (CMV) in patients with moderate-to-severe UC can worsen colitis and be associated with corticosteroid refractoriness.1,2,3,4 Early diagnosis and proper intervention is therefore very important. However, the clinical diagnosis of CMV colitis is very difficult. The diagnosis of CMV colitis in UC patients can be confirmed by histology, which comprises either PCR or immunohistochemistry (IHC).5 However, tissue PCR for CMV is controversial because of the possibility for false positives.6 Although IHC staining may be the best method to confirm CMV colitis,7,8,9 it takes several days for this test to yield results, and could be associated with hemorrhage or perforation.10,11,12 Many clinicians have tried to identify the best method of diagnosing CMV colitis. With this in mind, I read the study of Chun et al.13 with great interest. They assessed the clinical utility of the CMV antigenemia assay for the diagnosis of CMV colitis and predicting the outcomes of patients with UC. According to their results, CMV colitis was more common in patients with positive CMV antigenemia (eight patients, 66.7%), and this association was statistically significant (P=0.001). The results were consistent with other similar studies, which showed low sensitivity and high specificity.12,14 They suggested 2 pp65-positive cells per 2×105 polymorphonuclear leukocytes as a cut-off value, and this is very meaningful. However, among patients with positive antigenemia assay results, three did not have CMV colitis and four with negative results had CMV colitis. In addition, ganciclovir was considered only in tissue-confirmed cases with steroid refractoriness. I am therefore curious as to whether these results have any clinical significance in the diagnosis of CMV colitis. Can the antigenemia assay substitute histologic evaluation? I believe that Chun et al. did not clearly demonstrate the significance of the CMV antigenemia assay without histology in the diagnosis of CMV colitis. Even in cases where the antigenemia assay was negative, they considered antiviral therapy if tissues showed CMV colitis. Therefore, I think we eventually need endoscopy and tissue confirmation in steroid refractory UC patients to decide upon antiviral therapy. One study suggested that the CMV antigenemia assay has a diagnostic role only in conjunction with endoscopic findings.14 I agree with this opinion; however, considering the high rate of false positive results of PCR for CMV, it could be helpful for diagnosis only when tissue PCR is positive and IHC staining is negative. The role of CMV in the exacerbation of UC is still under debate.6 Several studies have reported that CMV reactivation could be improved without antiviral treatment,15,16 and others have suggested that in patients who are resistant to corticosteroids, antiviral therapy should be considered if they are positive for CMV in tissue studies.17 Chun et al. also demonstrated a significant association of CMV antigenemia with steroid refractoriness, and suggested early rescue therapy.13 CMV antigenemia could be a good predictor of clinical outcomes such as steroid refractoriness. However, it is limited in the diagnosis of CMV colitis. Despite these limitations, I think it could be very helpful in some cases. Therefore, we need to define the proper indication of the CMV antigenemia assay in the diagnosis of CMV colitis.

Incidence and risk factors for cytomegalovirus (CMV) reactivation following autologous hematopoietic stem cell transplantation in children.

There are limited data on the incidence of CMV reactivation following autologous HSCT (AHSCT) in children. We retrospectively reviewed the incidence and risk factors for CMV reactivation in 72 children who received AHSCT. Twenty-two patients (31%) had positive CMV antigenemia at a median of 23 days (12-31) following transplant. Four patients (6%) required preemptive therapy and all episodes resolved. None of the patients developed CMV disease. Only being CMV seropositivity prior to transplant was significantly associated with CMV reactivation (P < 0.001). The incidence of CMV reactivation following pediatric AHSCT is low, and surveillance beyond 30 days is not needed.

Clinical utility of cytomegalovirus antigenemia assay and blood cytomegalovirus DNA PCR for cytomegaloviral colitis patients with moderate to severe ulcerative colitis

Background and aimsClinical usefulness of cytomegalovirus (CMV) antigenemia assay and blood CMV polymerase chain reaction (PCR) in patients with ulcerative colitis (UC) needs to be evaluated. MethodsMedical records of moderate to severe UC patients between January 2001 and December 2012 were reviewed retrospectively. Diagnostic performances of CMV antigenemia assay and blood PCR to predict CMV colitis, and clinical outcome according to the results were analyzed. CMV colitis was diagnosed by H&E staining and/or CMV immunohistochemistry. ResultsOf the 229 study subjects, 83 patients (36.2%) had CMV colitis. The sensitivity and specificity of CMV antigenemia assay were 47.0% and 81.7%, and those of blood CMV DNA PCR were 44.3% and 87.9%, respectively. If either CMV antigenemia or PCR was positive in the presence of significant ulcers, the sensitivity and specificity of having CMV colitis were 67.3% and 75.7%, respectively, with the area under the receiver operating characteristic curve value of 0.717. Among patients with significant ulcers, positive CMV antigenemia (33/50 [66.0%] vs. 31/102 [30.4%]; p<0.001) and positive blood CMV PCR (25/37 [67.6%] vs. 24/86 [27.9%]; p<0.001) showed significantly higher probability of CMV colitis than blood test-negative patients. UC-CMV colitis patients with positive CMV antigenemia showed significantly higher rate of colectomy than those with negative antigenemia (13/39 [33.3%] vs. 5/44 [11.4%]; p=0.015). ConclusionsAlthough CMV antigenemia and blood CMV PCR showed low sensitivity for diagnosing CMV colitis, the specificity values were high. Among UC-CMV colitis patients, CMV antigenemia showed significant association with subsequent colectomy.

Inmune Reconstitution After Autologous Stem Cell Trasplantation: Is There Any Difference Between HIV+ and HIV- Patients?

AbstractAbstract 4665 Introduction:Little is known about immune reconstitution (IR) of HIV+ adult patients treated with HAART and high-dose chemotherapy followed by autologous stem cell transplantation (ASCT). Aims:To compare the IR in HIV+ and HIV- patients treated with ASCT, and to correlate it with clinical outcome. Material and Methods:From January 2007 to January 2011 all HIV+ patients with lymphoma or multiple myeloma treated with ASCT where prospectively included. HIV- patients with lymphoma or multiple myeloma treated with ASCT were included as control. IR lymphocytes (Ly) subsets in peripheral blood were quantified by flow cytometry (FACScan, Becton-Dickinson Immunocytometry Systems, San Jose, CA). Naïve ly, memory ly, memory-activated ly, effector ly, NK cytotoxic ly, B naïve ly and B memory ly were quantified at the time of transplantation as well as at 3, 6, 12 and 18 months after ASCT. Additionally, immunoglobulin value, neutrophil and platelet engraftment (>0.5×109/L and >20×109/L respectively) and infectious complications were recorded in both groups. The study was approved by the local Ethics Committee. Results:We included 14 patients, 6 HIV+ and 8 HIV-. All this patients were in complete remission at the time of the ASCT. All patients received BEAM conditioning regimen, except for Melphalan 200 in the case of MM. The median infused CD34 was 4,08×10e6 in HIV+ patients and 5.2 x10e6 in control patients. All HIV+ patients had undetectable viral load at the time of the ASCT. Values of ly populations are shown in Table 1. Median neutrophils days of engraftment: 11.5 days (11–13.75) in HIV- and 14 in HIV+ (12.75–17), platelets: 15 (13–28) and 30 (17–78) (p:≤0.05) respectively. Both groups reached IR at third month, while HIV+ group showed lower values especially for the T CD4 ly subgroup (not statistically significant). HIV+ patients had statistically significant lower values of CD4 memory ly and activated CD4 ly at 6th month, and lower values of NK ly at 3th month. On the other hand, we found lower values of B naïve Ly in HIV- patients at 6th month. There was no difference in the median value of immunoglobulin at 3, 6 and 12 months between both groups. Infections were more frequents in HIV+ patients: positive Aspergillus antigenemia (3/6 vs. 1/8), positive CMV antigenemia (3/6 vs. 1/6), fungal infection (2/6 vs. 0/8) and bacterial infections (5/ 6 vs. 2/8), nevertheless severe episodes didn’t shown differences, as well as disease free survival and mortality. Conclusions:In this series, IR was reached at the third month in both HIV + and HIV- patients, with non-significant lower values for HIV+ patients. Despite infections were more frequent in HIV+ patients, this was not associated with a higher mortality.TimeM0M3M6M12VIH−VIH+VIH−VIH+VIH−VIH+VIH−VIH+Naive/memory4+45rah+62l+19,090,67,45,319,65,147,649,04+45RO+147,7121,4306,1109,8191,5139,8272,8283,04+45RO+DR+24,28,034,215,212,114,617,943,38+45rah+62l+28,170,027,489,139,867,997,2117,18+45RO+137,7179,4373,7527,1256,374,1233,1500,0Activate ly4+DR+38+16,005,6513,107,353,977,3515,6521,594+DR-38+38,5630,47113,3329,13138,1430,2978,1376,404+DR+28,509,6920,0712,4911,9020,4132,1159,124+38+61,5268,6950,3743,6256,6653,98116,8797,608+DR+38+21,6830,0130,3196,254,7954,3412,0064,718+DR+31,7932,9949,9298,5615,90102,9424,70109,388+38+108,0680,25197,15225,7192,85166,0264,45395,62Effector8+28+57+23,5976,14116,378,68136,57181,1399,98246,208+28-57+52,04101,59247,56294,78116,43189,86100,27227,678+57+95,16160,53373,08299,04211,22408,65220,26365,708+45ra+62l-17,1580,60237,1778,10183,95123,5760,30157,078+28-103,9409,49360,08590,59244,20271,57170,83358,78T lyCD3+533,56543,26999,49694,31599,42955,371040,591327,12CD3+CD4+197,66241,66395,05220,15303,53150,27337,09329,00CD3+CD8+308,82294,04422,38411,50326,46792,85440,99733,56NK ly56+3-65,66101,30140,2765,2872,08104,61188,98217,7056l+3-51,2491,24125,0659,0958,3868,93179,06192,4056h+3-4,677,3521,2510,487,4220,2210,7036,16B ly19+27-IgD+,29,1612,3513,161,61108,8431,6026,9619+27+IgD+,41,324,341,51,083,8290,177,4419+27+IgD-,00,00,11,05,04,5710,28,00Median values of lymphocytes population studied. Yellow box remarked correspondsTo the statistically significant results (p:≤0,05) Disclosures:No relevant conflicts of interest to declare.

Clinical significance of quantitative cytomegalovirus detection in bronchoalveolar lavage fluid in lung transplant recipients

Cytomegalovirus (CMV) is an important pathogen after lung transplant (LTx) and may be associated with bronchiolitis obliterans syndrome (BOS). We assessed the outcome of LTx patients with CMV DNA-positive bronchoalveolar lavage (BAL) during surveillance. A single-center retrospective study was performed. Outpatients transplanted between September 2007 and February 2010, who had undergone at least 3 BALs, were included. CMV DNA load in BAL was measured by polymerase chain reaction (PCR). Monitoring of peripheral blood antigenemia was performed simultaneously. In total, 103 LTx patients underwent 1118 BALs. During median follow-up of 639 days (interquartile range, 495-780), 53 (51%) patients exhibited at least 1 positive CMV PCR in BAL. The incidence of positive CMV PCR varied post transplantation, with 6%, 30%, and 25% of BALs testing positive at <6 months, 6-24 months, and >24 months, respectively. Neither CMV BAL positivity, positive CMV antigenemia, nor dual positivity were significantly associated with BOS-free survival during follow-up. Patients with CMV-positive BAL more frequently developed CMV antigenemia in the first year (44% vs. 5%, respectively, log-rank P < 0.001). Detection of CMV-positive BAL after the sixth month appears common, but did not correlate with BOS-free survival after LTx in this study. An increased risk of developing blood antigenemia was observed in patients with positive CMV PCR in BAL, warranting close follow-up.

Analysis of cytomegaloviral antigenemia test and re-test after antiviral chemotherapy in patients with autoimmune and non-autoimmune diseases

To retrospectively analyze the cytomegalovirus (CMV) antigenemia test and re-test after antiviral chemotherapy in patients with autoimmune and non-autoimmune diseases. CMV Brite kit and indirect immunofluorescence were used to detect CMVpp65 antigenemia in 6471 peripheral blood leukocyte specimens from 5325 clinic and hospitalized patients with clinically suspicious CMV infections from May 2008 to February 2012. And the positive results were defined as episodes of systemic CMV activity. In 6471 EDTA-treated peripheral blood specimens, 948 (14.6%) were found with positive CMV antigenemia. The average positive rate from 13 kinds of autoimmune diseases was 34.9% (670/1922) in which systemic lupus erythematosus patients had the highest (52.4%, 551/1052). Meanwhile, the average positive rate from 12 kinds of non-autoimmune diseases was only 6.1% (144/2367) in which it was 17.3% (27/156) in patients with respiratory/acute renal failure, acquired immunodeficiency syndrome (AIDS) and kidney transplant recipients. And 189 patients with positive antigenemia were re-tested after antiviral chemotherapy and only 64 (33.9%) were converted negatively. Patients with autoimmune diseases have replaced traditionally immunocompromised patients, e.g. AIDS and kidney transplant recipient, to become the highest risk group of systemic CMV activity. Negative conversion rate of CMV antigenemia is low after antiviral chemotherapy.

Cytomegalovirus Disease in Kidney Transplant Recipients: Incidence, Clinical Profile, and Risk Factors

BackgroundCytomegalovirus (CMV) is one of the most frequently encountered opportunistic viral pathogens in renal transplantation. Approximately 60% of transplant recipients will have CMV infection and >20% will develop symptomatic disease. With the advancement of immunosuppression, variation in the occurrence and pattern of infections is possible. We described the incidence, clinical profile, outcome, and risk factors for development of CMV disease among renal transplant recipients. Patients and MethodsWe studied patients who underwent transplantation from January 2005–December 2009 admitted for CMV disease. CMV infection was present if the patient had at least 1 of the following: positive early antigen detection in blood or tissues, positive CMV antigenemia, or a 4-fold increase in pretransplantation CMV antibody titer. CMV disease was diagnosed if CMV infection was accompanied by clinical signs and symptoms. Descriptive statistics included measures of central tendency for continuous numerical variables and percentage-frequency distribution for categorical variables z test, Wilcoxon-Mann-Whitney test, and Fisher exact test were used to determine risk factors for CMV disease. ResultsAbout 1502 renal transplantations were done during the study period with mean follow-up of 33.8 months. CMV disease was confirmed in 85 (5.8%) recipients who developed 88 CMV disease episodes. Of the 85 patients who had CMV disease, 55% developed ≤3 months posttransplantation. Fever was the most common presenting symptom, 53% had coinfection, and case fatality rate was 11%. Risk factors that were statistically significant in the development of CMV disease were as follows: recipient/donor relationship (P = .0115), CMV donor+/recipient– (P = .004), and recent rejection treatment (P = .0084). ConclusionIncidence of CMV disease was 5.8% with fever as the most common presenting symptom and 55% developed CMV disease ≤3 months posttransplantation. Coinfection occurred in 53% and case fatality rate in 11%. Risk factors for developing CMV disease included CMV donor+/recipient– and recent acute rejection treatment.

Successful Conversion to Everolimus After Cytomegalovirus Infection in a Heart Transplant Recipient

Cytomegalovirus (CMV) infection remains a major problem in recipients with heart transplantation (HTx), because it may play a significant role in the development of cardiac allograft vasculopathy, which is one of the major causes of death after HTx. Valganciclovir (VGC) is effective for the treatment of CMV infection, but is often associated with neutropenia, especially when used with mycophenolate mophetil (MMF). We experienced an HTx recipient with positive CMV antigenemia who suffered progressive neutropenia after administration of VGC. We switched MMF to everolimus (EVL) and assay for CMV antigenemia was constantly negative even after discontinuation of VGC. In all other 14 HTx recipients who received EVL for any reason, we found that assay for CMV antigenemia remained negative throughout the period of EVL administration. Considering the prophylactic effect on CMV, EVL can not only be an alternative to rescue from comorbidity, but might also be indicated earlier especially in CMV-seronegative HTx recipients.

Risk factors for invasive mold infections following allogeneic hematopoietic stem cell transplantation: A single center study of 190 recipients

Invasive mold infection (IMI) is a major cause of infection-related mortality following allogeneic hematopoietic stem cell transplantation (allo-HSCT). We retrospectively analyzed 190 allo-HSCT recipients at Changhai Hospital between the y 2000 and 2007. The survival rate was evaluated with Kaplan-Meier curves. Logistic and Cox regression models were used for multivariate analyses. The 1(st) y cumulative incidence rate of IMI was 12.8%, and invasive aspergillosis was the most commonly observed IMI (85%). Multivariate logistic regression analyses showed that significant predictors of IMI were corticosteroid therapy (odds ratio (OR) 1.656, 95% confidence interval (CI) 1.047-2.621, p = 0.031), positive cytomegalovirus antigenemia (OR 5.301, 95% CI 1.902-14.772, p = 0.001), and secondary neutropenia (OR 5.250, 95% CI 1.741-15.834, p = 0.003). The mortality rate of IMI at 12 weeks after diagnosis was 60%. In Cox regression models, IMI-related mortality was related to the dose of corticosteroid (2 mg/kg/day or more) administered at the time of IMI diagnosis (hazards ratio (HR) 20.841, 95% CI 2.151-201.944, p = 0.009) and neutropenia (HR 7.043, 95% CI 1.186-41.827, p = 0.032). These data confirm previous findings that the incidence and mortality of IMI are mostly associated with immunodeficiency caused by immunosuppressive therapy or virus infection.