Cytomegalovirus infection as an underestimated trigger for checkpoint inhibitor-related pneumonitis in lung cancer: a retrospective study.

OBJECTIVES: Checkpoint inhibitor-related pneumonitis (CIP) is a rare but potentially fatal complication of immune checkpoint inhibitors (ICIs). At present, the mechanism of CIP is not completely clear. Cytomegalovirus (CMV) infection is widespread in the population. Chemotherapy and radiotherapy can lead to the reactivation of CMV. We aimed to investigate the association between CMV infection and CIP. MATERIALS AND METHODS: We retrospectively identified all lung cancer patients treated with ICIs at our institute from January 2016 to May 2020. The association between the development of CIP and CMV infection status was analyzed. RESULTS: Among 251 cases analyzed, 29 (11.6%) patients with CIP were identified, of whom 12 (4.78%) cases had grade 3-4 CIP. All 12 patients with grade 3-4 pneumonitis were CMV-IgG-positive, indicating a previous CMV infection. Except for one CMV-DNA-positive patient, the other patients were CMV-DNA-negative. All but one patient was CMV pp65 antigen-positive, indicating an early reactivation of the virus. The histological features of CMV pneumonia were not found in all available lung tissues, including lung transplantation pathology in one patient and lung biopsies in three patients. Except for one patient who received delayed antiviral therapy, the symptoms improved after glucocorticoid combined with antiviral therapy. CONCLUSIONS: The use of ICIs can restore the immune function and cause an immune response to CMV antigen while the infection is still latent. Our study suggests that CIP may be an immune reconstitution syndrome associated with CMV infection. CMV infection may represent a potentially important trigger for CIP. Patients with severe CIP should be vigilant against CMV infection. The early use of glucocorticoid combined with antiviral therapy is pivotal to good prognosis.

Pp65 antigenemia and cytomegalovirus diagnosis in patients with lupus nephritis: report of a series.

INTRODUCTION: In contrast to organ transplantation, few studies correlate the monitoring of pp65 antigenemia with a diagnosis of cytomegalovirus (CMV) in patients with systemic lupus erythematosus (SLE). OBJECTIVE: To highlight the importance of CMV outside transplantation, we monitored pp65 antigenemia in a series of SLE patients. METHODS: From March 2015 to March 2016, SLE patients presenting kidney involvement, fever, and an unclear infection at hospital admission were monitored through pp65 antigenemia. The pp65 antigenemia assay, revealed by immunofluorescence, was correlated with clinical and laboratory findings. RESULTS: We included 19 patients with a suspected unclear infection. A positivity for pp65 antigenemia was found in seven patients (36.8%). The mean age was 33.5 ± 11.2 years, 16 (84%) were females, and 16 (84%) were black. Lymphopenia, anemia, and higher scores of SLEDAI were significantly more common in pp65-positive patients. Five patients received antiviral therapy with ganciclovir. Although receiving specific CMV treatment, one patient died because of suspected CMV disease. CONCLUSIONS: Pp65 antigenemia might be relevant in SLE patients, and studies with a greater number of patients are needed in order to establish sensitivity and specificity of pp65 antigenemia in different clinical contexts of SLE patients.

Pp65 antigenemia and cytomegalovirus diagnosis in patients with lupus nephritis: report of a series / Antigenemia pp65 e diagnóstico de citomegalovírus em pacientes com nefrite lúpica: série de casos

ABSTRACT Introduction: In contrast to organ transplantation, few studies correlate the monitoring of pp65 antigenemia with a diagnosis of cytomegalovirus (CMV) in patients with systemic lupus erythematosus (SLE). Objective: To highlight the importance of CMV outside transplantation, we monitored pp65 antigenemia in a series of SLE patients. Methods: From March 2015 to March 2016, SLE patients presenting kidney involvement, fever, and an unclear infection at hospital admission were monitored through pp65 antigenemia. The pp65 antigenemia assay, revealed by immunofluorescence, was correlated with clinical and laboratory findings. Results: We included 19 patients with a suspected unclear infection. A positivity for pp65 antigenemia was found in seven patients (36.8%). The mean age was 33.5 ± 11.2 years, 16 (84%) were females, and 16 (84%) were black. Lymphopenia, anemia, and higher scores of SLEDAI were significantly more common in pp65-positive patients. Five patients received antiviral therapy with ganciclovir. Although receiving specific CMV treatment, one patient died because of suspected CMV disease. Conclusions: Pp65 antigenemia might be relevant in SLE patients, and studies with a greater number of patients are needed in order to establish sensitivity and specificity of pp65 antigenemia in different clinical contexts of SLE patients.

RESUMO Introdução: Diferentemente do transplante de órgãos, poucos estudos correlacionam o monitoramento da antigenemia pp65 com o diagnóstico de citomegalovírus (CMV) em pacientes com lúpus eritematoso sistêmico (LES). Objetivo: De modo a destacar a importância do CMV para além do transplante, monitorizamos a antigenemia pp65 em uma série de pacientes com LES. Métodos: De março de 2015 a março de 2016, pacientes com LES que apresentaram acometimento renal, febre e infecção indeterminada na internação foram monitorados através da antigenemia pp65. O ensaio de antigenemia, revelada por imunofluorescência, foi correlacionado com achado clínicos e laboratoriais. Resultados: Foram incluídos 19 pacientes com suspeita de infecção indeterminada. Positividade para antigenemia pp65 foi encontrada em sete pacientes (36,8%). A idade média foi de 33,5 ± 11,2 anos; 16 (84%) eram do sexo feminino e 16 (84%) eram negros. Linfopenia, anemia e escore de SLEDAI mais elevado foram significativamente mais comuns em pacientes pp65 positivos. Cinco pacientes receberam terapia antiviral com ganciclovir. Apesar de receber tratamento específico para CMV, um paciente com suspeita de doença por CMV veio a óbito. Conclusões: Antigenemia pp65 pode ser relevante em pacientes com LES, e estudos com maior número de pacientes são necessários para estabelecer a sensibilidade e a especificidade da antigenemia pp65 em diferentes contextos clínicos envolvendo pacientes com LES.

Clinical correlates of pp65 antigenemia monitoring in the first months of post kidney transplant in patients undergoing universal prophylaxis or preemptive therapy

Abstract Introduction: Human cytomegalovirus is a major cause of morbidity in kidney transplant patients. Objectives: We aimed to study viral replication and serological response in the first months post kidney transplant in patients undergoing universal prophylaxis or preemptive therapy and correlate the findings with the clinical course of Human cytomegalovirus infection. Patients and methods: Independent from the clinical strategy adopted for managing Human cytomegalovirus infection, prophylaxis versus preemptive therapy, the pp65 antigenemia assay and serological response were assessed on the day of transplantation, and then weekly during the first three months of post-transplant. Results: From the 32 transplant recipients, 16 were positive for pp65 antigenemia, with a similar incidence rate in each group. There were no positive results in the first three weeks of monitoring; the positivity rate peaked at week eight. There was a trend for a higher and earlier frequency of positivity in the universal prophylaxis group in which the course of the Human cytomegalovirus infection was also more severe. Despite the differences in clinical picture and in the initial immunosuppressant schedule, the serological response was similar in both groups. Conclusion: Routine monitoring during the first three post-transplant months has a positive impact on the early detection of Human cytomegalovirus viral replication allowing for timely treatment in order to reduce morbidity of the disease. The strategy of universal therapy employing intravenous ganciclovir was associated to a worse clinical course of the Human cytomegalovirus infection suggesting that the use of >10 cells/2 × 105 leukocytes as a cut-off in this setting may be inappropriate.

Clinical correlates of pp65 antigenemia monitoring in the first months of post kidney transplant in patients undergoing universal prophylaxis or preemptive therapy.

INTRODUCTION: Human cytomegalovirus is a major cause of morbidity in kidney transplant patients. OBJECTIVES: We aimed to study viral replication and serological response in the first months post kidney transplant in patients undergoing universal prophylaxis or preemptive therapy and correlate the findings with the clinical course of Human cytomegalovirus infection. PATIENTS AND METHODS: Independent from the clinical strategy adopted for managing Human cytomegalovirus infection, prophylaxis versus preemptive therapy, the pp65 antigenemia assay and serological response were assessed on the day of transplantation, and then weekly during the first three months of post-transplant. RESULTS: From the 32 transplant recipients, 16 were positive for pp65 antigenemia, with a similar incidence rate in each group. There were no positive results in the first three weeks of monitoring; the positivity rate peaked at week eight. There was a trend for a higher and earlier frequency of positivity in the universal prophylaxis group in which the course of the Human cytomegalovirus infection was also more severe. Despite the differences in clinical picture and in the initial immunosuppressant schedule, the serological response was similar in both groups. CONCLUSION: Routine monitoring during the first three post-transplant months has a positive impact on the early detection of Human cytomegalovirus viral replication allowing for timely treatment in order to reduce morbidity of the disease. The strategy of universal therapy employing intravenous ganciclovir was associated to a worse clinical course of the Human cytomegalovirus infection suggesting that the use of >10 cells/2×105 leukocytes as a cut-off in this setting may be inappropriate.

Comparison of a rapid cytomegalovirus pp65 antigenemia assay revealed by immunofluorescence to an in-house assay revealed by immunoperoxidase for diagnosis in solid organ transplant recipient patients.

Cytomegalovirus (CMV) antigenemia is still one of the two major assays available for diagnosis and monitoring of CMV infections. A commercial rapid test recently available in Brazil for quantification of human cytomegalovirus pp65 antigenemia revealed by immunofluorescence technique was compared with the original in-house method revealed by immunoperoxidase in patients receiving solid organ transplants. Of 80 blood samples tested for CMV antigenemia, 34 (42.5%) were positive: commercial assay detected 33 (97%) and in-house assay detected 20 (58.8%) samples. The numbers of positive cells in the two assays were different, with a median of 4.5 and 12 positive cells obtained by in-house and commercial kit, respectively. Discrepancies between assays occurred in 15 specimens from patients with low-grade antigenemia (median 6 positive cells). The assay-time was reduced in approximately 50% compared to in-house methodology. In conclusion, besides comparable results obtained for both assays, the commercial antigenemia assay provides more rapid and sensitive results.

Comparison of a rapid cytomegalovirus pp65 antigenemia assay revealed by immunofluorescence to an in-house assay revealed by immunoperoxidase for diagnosis in solid organ transplant recipient patients

Cytomegalovirus (CMV) antigenemia is still one of the two major assays available for diagnosis and monitoring of CMV infections. A commercial rapid test recently available in Brazil for quantification of human cytomegalovirus pp65 antigenemia revealed by immunofluorescence technique was compared with the original in-house method revealed by immunoperoxidase in patients receiving solid organ transplants. Of 80 blood samples tested for CMV antigenemia, 34 (42.5 percent) were positive: commercial assay detected 33 (97 percent) and in-house assay detected 20 (58.8 percent) samples. The numbers of positive cells in the two assays were different, with a median of 4.5 and 12 positive cells obtained by in-house and commercial kit, respectively. Discrepancies between assays occurred in 15 specimens from patients with low-grade antigenemia (median 6 positive cells). The assay-time was reduced in approximately 50 percent compared to in-house methodology. In conclusion, besides comparable results obtained for both assays, the commercial antigenemia assay provides more rapid and sensitive results.

Saliva as a source of HCMV DNA in allogeneic stem cell transplantation patients.

OBJECTIVE: The purpose of this study was to investigate the use of saliva for the identification of human cytomegalovirus (HCMV) in allogeneic hematopoietic stem cell transplant patients by real time PCR compared with blood. MATERIALS AND METHODS: Saliva and blood samples were sampled weekly in 30 allogeneic hematopoietic stem cell transplant patients until 100 days after transplant. Total genomic DNA, extracted from saliva and whole-blood samples, was used for HCMV real time PCR. Nonparametric tests were performed, and P value

Clinical correlations of human cytomegalovirus strains and viral load in kidney transplant recipients.

Little is known about clinical differences associated with cytomegalovirus (CMV) infection by distinct strains in renal transplant patients. Different clinical pictures may be associated with specific viral genotypes, viral load, as well as host factors. The objective of this study was to identify CMV strains to determine viral load (antigenemia), and their correlation with clinical data in renal transplant recipients. Seventy-one patients were enrolled, comprising 91 samples. After selection, polymorphonuclear cells were used to amplify and sequence the gB region of CMV DNA. The sequences were analyzed to ascertain the frequency of different genotypes. Additionally, the results of this study showed that the gB coding gene presents a great variability, revealing a variety of patterns: classical gB1 (1.4%), gB1V (46.4%), classical gB2 (35.2%), gB2V (2.8%), gB3 (1.4%), classical gB4 (4.9%) and gB4V (4.9%). The mean viral load in kidney transplant patient was 75.1 positive cells (1-1000). A higher viral load was observed in patients with genotype 4 infection. Statistically significant differences were detected between gB1 and gB4 (p=0.010), and between gB2 and gB4 (p=0.021). The average numbers of positive cells in relation to clinical presentation were: 34.5 in asymptomatic, 49.5 in CMV associated syndrome and 120.7 in patients with invasive disease (p=0.048). As a group, gB1 was the most frequent strain and revealed a potential risk for developing invasive disease. Viral load also seemed to be important as a marker associated with clinical presentation of the disease.

Long-term renal graft function and survival in patients with high-risk for cytomegalovirus infection receiving preemptive therapy.

BACKGROUND: Preemptive therapy reduces the risk of cytomegalovirus disease in high-risk kidney transplant patients. The advantage of this strategy is that only a fraction of patients receive antiviral drugs for a limited time, which decreases costs and toxicity but requires frequent monitoring and may not prevent complications of asymptomatic cytomegalovirus replication. MATERIAL AND METHODS: Long-term graft-function and patient survival of high-risk kidney transplant patients who received preemptive therapy guided by pp65 antigenemia was compared to those whose assay remained negative throughout the first post-transplant year. RESULTS: Between August 1997 and March 2005, 24 of 272 patients were CMV D+/R-. Thirteen of the 24 (54.2%) developed a positive CMV assay during follow-up; the time between transplant and first positive antigenemia was 66.7 +/- 58.3 days (range 29-251 days). Four patients developed symptoms associated with CMV, one of whom succumbed from complications of CMV neumonitis. Overall, no significant differences were observed in SCr, eGFR, delta SCr, and delta eGFR during a 60-month followup between patients who developed CMV infection or disease and those who remained pp65 antigenemia-negative throughout the first 12 post-transplant months. Additionally, no deaths or graft loss occurred during the long-term follow up of this cohort. CONCLUSIONS: Our results suggest that in this high risk group of kidney transplant recipients, treating CMV replication using a preemptive strategy during the first posttransplant year is associated with a low rate of CMV complications and probably interferes with the alleged long-term negative indirect effects of CMV on kidney function and survival.

Detection of free circulating Epstein-Barr virus DNA in plasma of patients with Hodgkin's disease.

CONTEXT AND OBJECTIVE: Free circulating Epstein-Barr virus (EBV) DNA is often present in the plasma of Hodgkins disease patients. The aim here was to evaluate the prevalence of this finding, its correlation with the immunohistochemical expression of LMP-1 (latent membrane protein 1) and the influence of other clinical factors. DESIGN AND SETTING: Prospective study in two public tertiary institutions: Hematology Service, Universidade Federal do Rio de Janeiro, and Oncology Service, Instituto Nacional do Câncer, Rio de Janeiro. METHODS: A cohort of 30 patients with newly diagnosed Hodgkins disease was studied. The control group consisted of 13 healthy adult volunteers. EBV DNA was determined by conventional polymerase chain reaction (PCR). RESULTS: The median age was 28 years, and 16 patients were women. Advanced disease was present in 19 patients, and six were HIV-positive. EBV DNA was present in the plasma of 13 patients and one control (43% versus 8%, p = 0.03). EBV DNA prevalence was higher in HIV-positive patients (100% versus 29%, p = 0.0007) and those with advanced disease (63% versus 9%, p = 0.006). Among HIV-negative patients alone, EBV DNA prevalence remained higher in those with advanced disease. EBV DNA was found in 10/11 patients with LMP-1 expression in the lymph nodes, and in 3/19 without LMP-1 expression (kappa coefficient = 0.72). CONCLUSION: EBV DNA was present in 91% of patients with EBV-associated Hodgkins disease, and in all patients with HIV-associated Hodgkins disease. EBV DNA prevalence was higher in patients with advanced disease, irrespective of HIV status.

Detection of free circulating Epstein-Barr virus DNA in plasma of patients with HodgkinÆs disease / Detecção do DNA livre circulante do vírus Epstein-Barr no plasma de pacientes com doença de Hodgkin

CONTEXT AND OBJECTIVE: Free circulating Epstein-Barr virus (EBV) DNA is often present in the plasma of HodgkinÆs disease patients. The aim here was to evaluate the prevalence of this finding, its correlation with the immunohistochemical expression of LMP-1 (latent membrane protein 1) and the influence of other clinical factors. DESIGN AND SETTING: Prospective study in two public tertiary institutions: Hematology Service, Universidade Federal do Rio de Janeiro, and Oncology Service, Instituto Nacional do Câncer, Rio de Janeiro. METHODS: A cohort of 30 patients with newly diagnosed HodgkinÆs disease was studied. The control group consisted of 13 healthy adult volunteers. EBV DNA was determined by conventional polymerase chain reaction (PCR). RESULTS: The median age was 28 years, and 16 patients were women. Advanced disease was present in 19 patients, and six were HIV-positive. EBV DNA was present in the plasma of 13 patients and one control (43 percent versus 8 percent, p = 0.03). EBV DNA prevalence was higher in HIV-positive patients (100 percent versus 29 percent, p = 0.0007) and those with advanced disease (63 percent versus 9 percent, p = 0.006). Among HIV-negative patients alone, EBV DNA prevalence remained higher in those with advanced disease. EBV DNA was found in 10/11 patients with LMP-1 expression in the lymph nodes, and in 3/19 without LMP-1 expression (kappa coefficient = 0.72). CONCLUSION: EBV DNA was present in 91 percent of patients with EBV-associated HodgkinÆs disease, and in all patients with HIV-associated HodgkinÆs disease. EBV DNA prevalence was higher in patients with advanced disease, irrespective of HIV status.

CONTEXTO E OBJETIVO: O DNA do vírus Epstein-Barr (EBV) está freqüentemente presente no sangue periférico de pacientes com doença de Hodgkin. O objetivo deste estudo foi avaliar a prevalência deste achado, e correlacioná-lo com a expressão imunoistoquímica da LMP-1 (latent membrane protein 1) e a presença de outros fatores clínicos. TIPO DE ESTUDO E LOCAL: Estudo prospectivo realizado no Serviço de Hematologia da Universidade Federal do Rio de Janeiro e no Serviço de Oncologia do Instituto Nacional do Câncer, Rio de Janeiro, Brasil. MÉTODOS: Trinta pacientes com doença de Hodgkin recém-diagnosticada foram estudados, assim como um grupo controle composto por 13 indivíduos saudáveis. O DNA do EBV no plasma foi determinado pela reação em cadeia da polimerase (PCR) convencional. RESULTADOS: A idade mediana foi 28 anos e 16 pacientes eram do sexo feminino. A doença disseminada esteve presente em 19 pacientes e seis eram HIV+. O DNA do EBV foi detectado no plasma de 13 pacientes e um controle (43 por cento versus 8 por cento, p = 0,03). A prevalência do DNA do EBV foi maior nos pacientes HIV+ (100 por cento versus 29 por cento, p = 0,0007) e naqueles com doença disseminada (63 por cento versus 9 por cento, p = 0,006). Quando somente os pacientes HIV-negativos foram analisados, a prevalência do DNA do EBV permaneceu maior nos pacientes com doença disseminada. A prevalência do DNA do EBV variou de acordo com o subtipo histológico: foi de 32 por cento nos pacientes com esclerose nodular e de 100 por cento nos pacientes com celularidade mista e depleção linfocítica (p = 0,02). O DNA do EBV foi encontrado em 10/11 pacientes com a expressão da LMP-1 em linfonodos, e em 3/19 pacientes sem a expressão da LMP-1 (coeficiente de kappa = 0,72). CONCLUSÕES: O DNA circulante do EBV foi detectado no plasma de 91 por cento dos pacientes com doença de Hodgkin associada ao EBV, e em todos os pacientes com doença de Hodgkin associada ao HIV. A prevalência do DNA circulante do EBV foi detectado no plasma de 91% dos pacientes com doença de Hodgkin associada ao EBV, e em todos os pacientes com doença de Hodgkin associada ao HIV. A prevalência do DNA circulante do EBV foi maior nos pacientes com doença avançada, independentemente do status para o HIV.

[Presence of circulating cytomegalic cells in HIV negative immunosuppressed individuals following cytomegalovirus infection]. / Utilidad de la detección de células citomegálicas circulantes en pacientes inmunosuprimidos VIH negativos en el control de la infeccin por citomegalovirus.

OBJECTIVE: Immunofluorenscence methods to detect pp65 antigenemia were implemented for identifying the circulating virus-infected cells in individuals known to have cytomegalovirus infection and disease symptoms. MATERIAL AND METHODS: Between December-2002 and July-2003, 110 peripheral blood samples were obtained from 46 immunosuppressed patients. pp65 antigenemia and the presence of circulating cells were determined by indirect immunofluorescence using a commercial kit to detect CMV pp65 antigen in peripheral blood leukocytes. Antigenemia was positive when one or more cells was observed with multilobulated, homogenous fluorescent stain in the nucleus. The presence of infected circulating cells (peripheral blood mononuclear cells) was determined when an extended pattern of fluorescent stain was observed throughout the cytoplasm in cells of 35 to 50 microm. RESULTS: Eight antigenemias from 7 patients (15%) were positive. Of these, 4 (57%) were also positive for circulating infected cells and consisted of 3 kidney transplant recipients and 1 liver transplant recipient. The number of positive cells in antigenemia was greater in kidney-transplant recipients than in the rest of immunosupressed patients (457 vs. 1.96, p < 0.005). No association was seen between the presence of infected circulating cells, morbidity, mortality or the development of GVHD (p < 0.001). CONCLUSION: No correlation was observed between the presence of infected cells, antigenemia and mortality. To substantiate the lack of correlation amongst these factors, prospective studies with larger sample sizes are necessary. These studies will aid in better defining the clinical application in immunosupressed patients.

Surveillance of cytomegalovirus infection in haematopoietic stem cell transplantation patients.

OBJECTIVES: The aim of this study was to describe our experience in the control of active CMV infection following HSCT using two strategies of CMV infection treatment: ganciclovir universal prophylaxis at low doses and pre-emptive therapy with ganciclovir. METHODS: The surveillance was based on the monitoring of antigenaemia (AGM) and on a nested polymerase chain reaction (N-PCR) for the detection of CMV in both strategies. Forty-five recipients with malignant diseases and with a risk for CMV disease received universal prophylaxis (Group A). The non-treated group consisted of 24 patients, most of them with non-malignant diseases who did not receive universal prophylaxis (Group B). RESULTS: In Group A, the incidence of positive AGM was 51%, with a positive PCR of 68.9%. In Group B, the AGM positivity was 66.7% and that of N-PCR was 66.7%. CMV disease occurred in 6/55 patients (10.9%), with 2/36 (5.5%) from Group A and 4/19 (21%) from Group B. Two of these six patients (33.3%) died of CMV disease. CONCLUSIONS: Our result suggests that AGM and N-PCR can be used as markers for assessing the monitoring and the introduction pre-emptive therapy. This approach could prove to be more cost-effective than ganciclovir universal prophylaxis for treating CMV infection.

Sequential cytomegalovirus antigenemia monitoring in kidney transplant patients treated with antilymphocyte antibodies.

BACKGROUND: Antilymphocyte antibodies (ALA) use is related to disseminated cytomegalovirus (CMV) disease after kidney transplantation. Strict surveillance of CMV infection, preemptive antiviral treatment or concomitant ganciclovir and ALA use are proposed as an attempt to prevent related clinical complications. Our objective was to describe the pattern of CMV infection, based on sequential antigenemia detection, after ALA treatment. PATIENTS AND METHODS: Thirty renal transplant patients were prospectively screened for CMV infection after ALA treatment. CMV antigenemia (pp65 antigen detection) was monitored twice a week in the first month and weekly until 60 days after the beginning of ALA therapy. Any positive value of antigenemia was considered CMV infection. RESULTS: Twenty-eight (93.3%) patients were CMV positive (IgG) before transplantation. The mean duration of ALA treatment was 12.1+/-2.4 days. Positive antigenemia was detected in 24 (80%) patients, a mean of 52.5+/-15 days after transplant and 44.7+/-14 days after the beginning of ALA treatment. The median antigenemia count was 7 positive cells/300,000 neutrophils (range: 1-227). Antigenemia preceded clinical symptoms by 5.8 days (0-28 days). Eighteen (75%) of 24 positive patients received ganciclovir treatment: 8 patients (26.7%) for viral syndrome, 2 patients (33.3%) for invasive disease, and 8 patients (26.7%) as part of preemptive therapy, asymptomatic with high antigenemia values. Six pp65-positive patients with low counts were followed up until a negative result and remained asymptomatic without any specific treatment. CONCLUSION: CMV infection was frequent after ALA treatment in this group and generally occurred late after completion of treatment. Antigenemia was a reliable tool to guide preemptive treatment in these patients, and such strategy is an alternative option compared to the prophylactic use of ganciclovir with ALA treatment.

Comparison between RFLP-PCR and antigenemia for pp65 antigen for diagnosis of cytomegalovirus disease after kidney transplantation.

Cytomegalovirus (CMV) infection is the single most frequent infectious complication in renal transplant recipients. The purpose of this study was to analyze the diagnostic efficacy of PCR-RFLP compared to antigenemia for CMV disease (CMVD) in kidney transplant recipients. From November 2001 to February 2002, 19 renal adult transplant recipients were followed with weekly measurements of CMV pp65 antigen to monitor the activity of CMV from the week 4 to 12 posttransplantation. Only 4 (21.1%) patients did not develop viremia during the first 12 posttransplantation weeks. Active infection was observed in 15 patients (78.9%): asymptomatic viremia in 6 (31.6%) and CMVD in 9 (47%). All patients who developed CMVD showed positivity in both methods during the observation period. The number of positive cells ranged from 11 to 292 cells in patients with CMVD and one to eight cells among those with asymptomatic viremia. Both methods revealed 100% sensitivity for CMVD diagnosis. The specificity was 60% for antigenemia and 70% for PCR, with positive predictive values of 60% and 75%, respectively.

[Effectiveness of preemptive therapy with ganciclovir in recipients of renal transplants at high risk (R-/D+) for the development of cytomegalovirus disease]. / Efectividad de la terapia anticipada con ganciclovir en receptores de trasplante renal de alto riesgo (R-/D+) para desarrollo de enfermedad por citomegalovirus.

Current management of renal transplant recipients who are CMV seronegative (R-) and receive an organ from a seropositive donor (D+) is controversial. These patients are at high risk for CMV disease and are usually treated with ganciclovir prophylaxis at variable dose and duration. An alternative to this approach is to administer ganciclovir only to those patients who are identified by virological markers to be at the highest risk to develop the disease (preemptive therapy). This prospective trial was conducted to asses the value of preemptive therapy to prevent CMV disease in R-/D+ kidney transplant recipients on triple drug immunosuppression without antilymphocyte induction. Sixteen adults receiving their first kidney transplant were enrolled and followed with pp65 antigenemia assay performed biweekly for the first 16 postransplant weeks, and then monthly to complete 12 months. Ganciclovir (5 mg/kg/day i.v., for 15 days) was administered as preemptive therapy upon detection of one or more antigen-positive cells per 150 x 10(3) peripheral blood leucocytes examined. For those receiving preemptive therapy, pp65 antigenemia was also repeated after completion of the regimen. CMV antigenemia was detected in 7/16 patients. At mean follow-up of 9 months (4-12 m) none of the 16 patients developed CMV disease. CMV serology (IgM) became positive in all patients after the first antigenemia result. The last follow-up mean serum creatinine (SCr) level was similar in both groups (1.35 mg/dL). In CMV R-/D+, the use of preemptive therapy guided by pp65 antigenemia is effective in preventing CMV disease. By using this strategy, 9 of 16 patients were spared ganciclovir prophylaxis with no effect on rejection or CMV disease. The clinical benefit and cost/effectiveness of this strategy should be evaluated against universal prophylaxis in these high-risk patients.

Efectividad de la terapia anticipada con ganciclovir en receptores de trasplante renal de alto riesgo (R-/D+) para desarrollo de enfermedad por citomegalovirus / Effectiveness of preemptive therapy with ganciclovir in recipients of renal transplants at high risk (R-/D+) for the development of cytomegalovirus disease

Current management of renal transplant recipients who are CMV seronegative (R-) and receive an organ from a seropositive donor (D+) is controversial. These patients are at high risk for CMV disease and are usually treated with ganciclovir prophylaxis at variable dose and duration. An alternative to this approach is to administer ganciclovir only to those patients who are identified by virological markers to be at the highest risk to develop the disease (preemptive therapy). This prospective trial was conducted to asses the value of preemptive therapy to prevent CMV disease in R-/D+ kidney transplant recipients on triple drug immunosuppression without antilymphocyte induction. Sixteen adults receiving their first kidney transplant were enrolled and followed with pp65 antigenemia assay performed biweekly for the first 16 postransplant weeks, and then monthly to complete 12 months. Ganciclovir (5 mg/kg/day i.v., for 15 days) was administered as preemptive therapy upon detection of one or more antigen-positive cells per 150 x 10(3) peripheral blood leucocytes examined. For those receiving preemptive therapy, pp65 antigenemia was also repeated after completion of the regimen. CMV antigenemia was detected in 7/16 patients. At mean follow-up of 9 months (4-12 m) none of the 16 patients developed CMV disease. CMV serology (IgM) became positive in all patients after the first antigenemia result. The last follow-up mean serum creatinine (SCr) level was similar in both groups (1.35 mg/dL). In CMV R-/D+, the use of preemptive therapy guided by pp65 antigenemia is effective in preventing CMV disease. By using this strategy, 9 of 16 patients were spared ganciclovir prophylaxis with no effect on rejection or CMV disease. The clinical benefit and cost/effectiveness of this strategy should be evaluated against universal prophylaxis in these high-risk patients.