Cytomegalovirus Viremia In Patients Research Articles

Incidence of post-transplant cytomegalovirus viremia in patients receiving lungs after ex vivo lung perfusion

ObjectivesCytomegalovirus infection after lung transplant is associated with increased morbidity and mortality. Inflammation, infection, and longer ischemic times are important risk factors for cytomegalovirus infection. Ex vivo lung perfusion has helped to successfully increase the use of high-risk donors over the last decade. However, the impact of ex vivo lung perfusion on post-transplant cytomegalovirus infection is unknown. MethodsWe performed a retrospective analysis of all adult lung transplant recipients from 2010 to 2020. The primary end point was comparison of cytomegalovirus viremia between patients who received ex vivo lung perfusion donor lungs and patients who received non–ex vivo lung perfusion donor lungs. Cytomegalovirus viremia was defined as cytomegalovirus viral load greater than 1000 IU/mL within 2 years post-transplant. Secondary end points were the time from lung transplant to cytomegalovirus viremia, peak cytomegalovirus viral load, and survival. Outcomes were also compared between the different donor recipient cytomegalovirus serostatus matching groups. ResultsIncluded were 902 recipients of non–ex vivo lung perfusion lungs and 403 recipients of ex vivo lung perfusion lungs. There was no significant difference in the distribution of the cytomegalovirus serostatus matching groups. A total of 34.6% of patients in the non–ex vivo lung perfusion group developed cytomegalovirus viremia, as did 30.8% in the ex vivo lung perfusion group (P = .17). There was no difference in time to viremia, peak viral loads, or survival when comparing both groups. Likewise, all outcomes were comparable in the non–ex vivo lung perfusion and ex vivo lung perfusion groups within each serostatus matching group. ConclusionsThe practice of using more injured donor organs via ex vivo lung perfusion has not affected cytomegalovirus viremia rates and severity in lung transplant recipients in our center.

Cytomegalovirus Infection Management in Multivisceral and Intestinal Transplant: A Dual Institution Study

Intestinal transplant and multivisceral transplant were originally in pediatric populations and are relatively new procedures in adults. Despite increasing success rates in the immediate post-transplant period, infectious complications and acute and chronic rejection remain significant causes of morbidity and mortality. Previous research has shown cytomegalovirus (CMV) is the main cause of infection in this population. Due to the limited patient population, incidence of CMV viremia ranges widely and there is lack of universal protocol for treatment. This dual institution retrospective chart review between Henry Ford Hospital and Duke University analyzed adult intestinal and multivisceral transplant recipients between 2009 and 2019. Of the 32 patients identified and included in the study, 15 had CMV infection (46.9%). Of those with CMV infection, 5 (33.3%) had donor positive (D+)/recipient positive (R+) status; 5 had D-/R+; 4 had D+/R-; and one had D-/R-. There was no significant difference between mortality in those who had reported infection and not (80% vs 76.5%). The data from this study show significant rates of CMV viremia in patients undergoing intestinal transplant/multivisceral transplant with almost half of our study population having documented infection within 1 year of transplant, stressing the importance for universal protocol into CMV viremia treatment.

Incidence of Post-Transplant Cytomegalovirus Viremia in Patients Receiving Lungs After Ex Vivo Lung Perfusion

<h3>Purpose</h3> CMV infection following lung transplant (LTx) is associated with increased morbidity and mortality. Inflammation, infection and longer ischemic times are important risk factors for CMV infection. Ex vivo lung perfusion (EVLP) has helped to successfully increase utilization of high-risk donors over the last decade. However, the impact of EVLP on post-transplant CMV infection is unknown. <h3>Methods</h3> Single-center, retrospective analysis of all LTx recipients from 2010 to 2020. The primary endpoint was comparison of CMV viremia in recipients that received EVLP vs. non-EVLP donor lungs. CMV viremia was defined as CMV PCR > 1000 IU/mL within two years post-transplant. Secondary endpoints were time from LTx to CMV viremia, peak CMV PCR and survival. Outcomes were also compared between the different donor (D)-recipient (R) CMV serostatus matching groups. <h3>Results</h3> Included were 862 recipients of non-EVLP lungs and 389 recipients of EVLP lungs. There was no significant difference in the distribution of the CMV serostatus matching groups. 35.8% of patients in the non-EVLP group developed CMV viremia vs. 31.9% in the EVLP group (p=0.18). Median time to CMV viremia was 234 days [IQR, 179-318] in non-EVLP and 249 days [IQR, 186-313] in EVLP group (p=0.5). The mean±SD peak viremia was 4.1±0.8 log₁₀ IU/mL in the non-EVLP group and 4.2±0.8 log₁₀ IU/mL in the EVLP group (p=0.4). There was also no difference in survival of the viremic patients between the groups (log-rank p=0.8). All outcomes were similar when comparing non-EVLP and EVLP patients within each serostatus matching group (Fig.1). <h3>Conclusion</h3> Lung transplant activities have significantly increased with the use of high-risk donor lungs evaluated on EVLP. The practice of utilizing more injured donor organs via EVLP has not affected CMV viremia rates and severity in lung transplant recipients. EVLP could further provide the opportunity to pre-treat donor lungs prior to implantation, perhaps decreasing incidence of post-transplant CMV infection.

Outcomes After Living Donor Liver Transplantation in Pediatric Patients with Inherited Metabolic Diseases.

BackgroundThere is no consensus about the long-term prognosis of pediatric patients with a variety of rare liver diseases but with inherited metabolic diseases (IMDs). We retrospectively reviewed the developmental outcomes of patients with IMDs undergoing living donor liver transplantation (LDLT).Material/MethodsBetween May 2001 and December 2020, of 314 pediatric patients who underwent LDLT, 44 (14%) had IMDs. The median age at LDLT was 3.0 years old (range 0–15.0 years). Associations between the post-transplant complications and graft survival rate in patients with IMDs and biliary atresia (BA) were calculated. We evaluated the safety of LDLT from heterozygous carrier donors, the prognosis of patients with IMDs who have metabolic defects expressed in other organs, and developmental outcomes of patients with IMDs.ResultsThe 10-year graft survival rates in patients with IMDs and BA were 87% and 94%, respectively (P=0.041), and the causes of graft failure included pneumocystis pneumonia, acute lung failure, hemophagocytic syndrome, hepatic vein thrombosis, portal vein thrombosis, and sepsis. The rate of post-transplant cytomegalovirus viremia in patients with IMDs was higher than that of patients with BA (P=0.039). Of 39 patients with IMDs, 15 patients (38%) had severe motor and intellectual disabilities in 4 patients, intellectual developmental disorders including epilepsy in 2, and attention-deficit hyperactivity disorder in 2. Of 28 patients with IMDs, 13 (46%) needed special education.ConclusionsThe long-term outcomes of LDLT in patients with IMDs are good. However, further long-term social and educational follow-up regarding intellectual developmental disorders is needed.

Ganciclovir Therapy for CMV Viremia in a Patient on VV ECMO With COVID-19 After Treatment With Tocilizumab

Ganciclovir Therapy for CMV Viremia in a Patient on VV ECMO With COVID-19 After Treatment With Tocilizumab

Cytomegalovirus Reactivation in Children with Hemoglobinopathies Who Undergo Hematopoietic Cell Transplantation with Distal Alemtuzumab

Introduction Cytomegalovirus (CMV) viremia after allogeneic hematopoietic cell transplant (HCT) is associated with substantial morbidity. In vivo T cell depletion with alemtuzumab is a known risk factor for CMV reactivation. After observing very early CMV viremia in patients who received distal alemutuzumab in preparation for HCT for hemoglobinopathies, we implemented a quality improvement project to decrease the burden of CMV in this population. Objective To describe patterns of CMV reactivation before and after changing our CMV prophylaxis and surveillance strategies. Methods We reviewed medical records of children undergoing HCT for sickle cell disease (SCD) or beta thalassemia at Children`s Hospital of Philadelphia between 2007-2018, who received distal alemtuzumab containing conditioning regimens. Patients received alemtuzumab (48 mg, starting ∼22 days before transplant) with fludarabine and melphalan. Beginning in February 2014, CMV seropositive (CMV+) patients received prophylaxis with valganciclovir from completion of alemtuzumab through day -1 and foscarnet starting on day 0, as well as weekly CMV surveillance beginning with alemtuzumab administration. Rates of CMV reactivation, as well as balancing metrics [time to engraftment and rate of acute kidney injury (AKI) within 100 days post-HCT] were evaluated before and after implementation of this preventive approach. Results Twenty-nine children were included in the analysis. The median age was 11.1 (range: 3.1 to 17.3) years at HCT; 22 (75.9%) patients had SCD and 8 (24.1%) had beta thalassemia. All patients received bone marrow grafts, 22 (75.9%) from HLA-identical siblings and 7 (24.1%) from unrelated donors. Prior to HCT, 13 patients were CMV+. Of those, 11 (84.6%) developed CMV reactivation (7/7 pre-intervention and 4/6 post-intervention). Time from alemtuzumab start to CMV reactivation, regardless of prophylactic strategy, is shown in Figure 1. CMV reactivation occurred at a median of 4 (range: -11 to +13) days after planned HCT. During the post-intervention period, CMV reactivation was identified in 2 patients prior to the start of the proximal cytotoxic phase of conditioning and HCT was delayed until viremia cleared. One CMV seronegative patient developed CMV viremia 47 days post-HCT. Median time to engraftment was similar before and after the intervention (12.5 versus 13 days), as was the proportion of patients with AKI (3/7 versus 1/6). Conclusion In this cohort, rates of CMV viremia were high and CMV reactivation often occurred very early in the transplant course. In two cases, CMV reactivation was identified prior to transplant day, necessitating a delay in HCT. Consideration should be given to implementing a program of screening or prophylaxis beginning as early as the start of alemtuzumab administration in CMV+ patients. Further research is needed to determine the optimal prophylactic strategy.

MOLECULAR DETECTION OF CYTOMEGALOVIRUS IN A SAMPLE OF IRAQI PATIENTS WITH ACUTE LEUKEMIA AND STEM CELL TRANSPLANTATION

Background: Acute leukemia and hematopoietic stem cell transplantation are risk factors for opportunistic infection and reactivation of many latent infection like cytomegalovirus. Objective: Detection and quantification of cytomegalovirus viremia in patients with acute leukemia after induction chemotherapy and post allogeneic stem cell transplantation patients. Methods: A prospective study enrolled 61 patients with acute leukemia. Forty-eight of them evaluated while induction chemotherapy (group I), while the other 13 within 1-year post bone marrow transplantation (BMT) (group II). In addition, 30 apparently healthy individuals were recruited as (control group), blood samples were collected from all groups. Viral DNA was extracted from 1 ml plasma samples, and then, cytomegalovirus DNA was detected and quantitatively assessed by Taqman quantitative real-time PCR. Results: Twelve (25%) out of 48 patients in group I, 2 (15.4%) out of the 13 patients in group II, and 2 (6.7%) out of 30 in the control group had positive cytomegalovirus viremia. The mean cytomegalovirus viremia was 5.192x102, 2.71x102 and 1.60x102 copies/ml for group I, group II and controls respectively, p=0.056. Conclusion: There is a relatively high prevalence of cytomegalovirus viremia in Iraqi patients with acute leukemia after chemotherapy and post BMT. Real-time PCR assay is helpful for early diagnosis of cytomegalovirus viremia in leukemic patients and used to monitor post BMT patients at risk for cytomegalovirus disease. Keywords: HCMV, acute leukemia, stem cell transplantation, real-time PCR Citation: Al-Toban HA, Al-Marsomy HD, Al-Obaidi AB, Al Tameemi WF, Mohammed MA, Al-Saeed RM, Al-Shemary IK. Molecular detection of cytomegalovirus in a sample of iraqi patients with acute leukemia and stem cell transplantation. Iraqi JMS. 2018; 16(3): 344-352. doi: 10.22578/IJMS.16.3.14

Comparison of Roche and Abbott Cytomegalovirus Quantitative PCR Assays in Allogeneic Hematopoetic Cell Transplant Recipients

BackgroundHuman Cytomegalovirus (CMV) infection is prevalent in patients undergoing transplantion (Tx) and carries significant morbidity and mortality. Quantification of CMV viremia has improved with the use of standardized international units and new commercial real time PCR assays. This study compares the current Roche cobas AmpliPrep/cobas TaqMan CMV test (TM assay) and Abbott Molecular RealTime CMV Investigational Use Only assay (ART assay) for quantification of CMV viremia in patients receiving allogeneic hematopoietic stem cell transplants (aHSCT).MethodsProspective CMV positive patients, planned for aHSCT, were consented prior to Tx and followed weekly up 12 weeks post-transplant (PT) and once ~3 months PT. Matched paired plasma samples were processed and analyzed per manufacturer instructions, Henry Ford clinical laboratory processed the samples using the TM assay and the McKinnon Research Laboratory processed the paired samples using the ART assay. Parametric and non-parametric analyses were conducted as appropriate.ResultsFourteen patients enrolled, 1 patient withdrew after entering, 1 patient died after 9 weeks PT (primary disease). Patients received peripheral blood stem cells and 84.6% received myeloablative chemotherapy. In paired samples, quantifiable CMV by TM and ART assays was detected in 6 (5 treated) vs. 8 of 13 patients respectively. ART assay detected CMV in all patients with positive paired samples, 1 detected in an unpaired sample and in 2 patients missed by TM assay (P = 0.021). Assays also differed in samples with no detection, detectable and quantifiable CMV viremia, with more frequent detection in the ART assay (P = 0.009). Time to quantifiable viremia PT by TM and ART assays was a median of 5 vs. 3 weeks (P = 0.026). Bland-Altman plot shows higher viremia levels quantified using the ART assay (P = 0.023). After week 4 PT, ART assay results inversely correlated with platelets counts (P = 0.013). CMV viremia tended to persist 1.9 weeks longer using ART vs.. TM assay (P = 0.07).ConclusionCMV viremia was quantified earlier, at higher levels and persisted in patients with aHSCT using the ART assay compared with the TM assay. Further study is warranted to determine clinical impact of ART assay on the management of CMV viremia.Disclosures J. Mckinnon, Abbott Molecular: Speaker’s Bureau, Grant recipient and Speaker honorarium D. Lucic, Abbott Molecular: Employee, Salary

Cytomegalovirus viremia in patients who were infected with Human Immunodeficiency Virus

Cytomegalovirus viremia in patients who were infected with Human Immunodeficiency Virus

Donor T‐cell chimerism and early post‐transplant cytomegalovirus viremia in patients treated with myeloablative allogeneic hematopoietic stem cell transplant

Cytomegalovirus (CMV) is a common infection after myeloablative allogeneic hematopoietic stem cell transplant (M-alloHSCT). Achievement of complete donor T-cell chimerism (CDC-T) post transplant is a measure of immune reconstitution. We investigated the association between CDC-T post M-alloHSCT and the incidence of CMV viremia. We retrospectively reviewed all CMV and chimerism results of 47 patients for the first 6 months post M-alloHSCT. CDC-T was analyzed as a time-varying covariate for association with post M-alloHSCT CMV viremia. CMV viremia occurred in 15 (32%) and CDC-T was achieved in 38 (81%) recipients within the first 6 months post M-alloHSCT. On univariable analysis, increased CMV viremia was seen among patients with CDC-T (hazard ratio 2.81 [P = 0.07, 95% confidence interval = 0.93-8.52]). A 30-day landmark analysis showed that the incidence of CMV viremia at 6 months (regardless of recipient CMV serostatus) was 50% among those who had achieved CDC-T by day 30, and 23% among those who had not (P = 0.06). We conclude that shorter time to CDC-T may be associated with higher risk of CMV viremia. If confirmed in a larger cohort, this might be a marker for risk stratification in the management of CMV in this population.

Is Cytomegalovirus Testing of Blood Products Still Needed for Hematopoietic Stem Cell Transplant Recipients in the Era of Universal Leukoreduction?

Hematopoietic stem cell transplantation (HSCT) recipients are a high-risk, immunocompromised group of patients who receive frequent transfusions after transplantation. Transfusion of cytomegalovirus (CMV)-negative blood products has long been the standard of care to prevent transfusion-transmitted CMV in this patient population. Leukoreduction of blood products before transfusion has been shown to significantly reduce the risk of transfusion-transmitted CMV. In the era of universal leukoreduction in Canada, the need for CMV testing of blood products remains unclear. We sought to identify whether there is a difference in transfusion-transmitted CMV viremia in patients receiving only leukoreduced versus CMV-negative and leukoreduced blood products in HSCT recipients. Patients who were CMV negative and received an allogeneic HSCT from a CMV-negative donor between October 1, 1999 and June 30, 2012 were included in the analysis. Transfusion data were collected from The Ottawa Hospital Blood Bank and Canadian Blood Services. CMV viremia was defined as PCR positivity. One hundred sixty-six patients were identified who met the inclusion criteria. Of these, 89 patients received an HSCT before January 2007, during the time when patients received leukoreduced and CMV-negative blood products. Seventy-seven patients received an HSCT after this time, receiving only leukoreduced blood products. The 2 groups did not differ in terms of age, gender, diagnosis, graft type, graft source, conditioning regimen, or ABO compatibility (P > .05). CMV viremia was detected in 3 patients who received CMV-negative leukoreduced blood products (3.37%) and in 1 patient who received only leukoreduced blood products (1.30%, P = .6244). Of the patients who developed CMV viremia, 2 developed suspected CMV disease. Both of these patients were transfused with CMV-negative blood products. Secondary outcomes, including total length of stay in hospital, admission to the intensive care unit, acute and chronic graft versus host disease, and 100-day nonrelapse mortality, did not differ between the groups. In the era of universal leukoreduction of blood products, this study demonstrates that testing for CMV-negative blood products is not needed for HSCT recipients.

Low cytomegalovirus-specific T-cell counts at reactivation are associated with progression to high-level viremia or disease in seropositive recipients of hematopoietic cell grafts from seropositive but not seronegative donors

Identifying patients who spontaneously resolve cytomegalovirus (CMV) reactivation could spare these patients from the toxicity of antiviral drugs such as ganciclovir. The role of CMV-specific T cells in clearing CMV viremia in patients who do not receive ganciclovir has not been evaluated. We assessed this in patients with CMV viremia between 50 and 50 000 genome copies/mL, because our threshold for initiating ganciclovir is 50 000 copies/mL. We enumerated CMV-specific T cells in 39 CMV seropositive hematopoietic cell transplantation (HCT) recipients within 4 days of the first positive CMV polymerase chain reaction (PCR). CMV-specific T cells were defined as cells that upon stimulation with CMV lysate or pp65 overlapping peptides produced interferon (IFN)-γ, tumor necrosis factor (TNF)-α or interleukin (IL)-2, alone or in combination. Among Donor (D+), Recipient (R+) patients, unifunctional CMV-specific CD4 T-cells were higher in patients who spontaneously resolved CMV viremia (did not receive ganciclovir) versus those who progressed (received ganciclovir) (median 0.20 versus 0.02/μL lysate-stimulated cells, P < 0.05, and 0.26 versus 0.05/μL pp65 peptide-stimulated cells, P<0.05). Among D- R+ patients, there was no difference between patients with spontaneous resolution or progression; all subsets of CMV-specific T cells measured were barely detectable, in both patients with spontaneous resolution and those with progression. Among D+ R+ patients (but not D- R+ patients), high CMV-specific CD4 T-cell counts identify patients who can spontaneously resolve CMV reactivation. In D- R+ patients, immune mechanisms other than T cells may control the progression from reactivation to high-level viremia/disease.

Donor T-Cell Chimerism and Early Post-Transplant Cytomegalovirus Viremia in Patients Treated with Myeloablative Allogeneic Hematopoietic Stem Cell Transplant

Background Cytomegalovirus (CMV) is a common infection after myeloablative allogeneic hematopoietic stem cell transplant (M-alloHSCT). Achievement of complete donor T-cell chimerism (CDC-T) post transplant is a measure of immune reconstitution. We investigated the association between CDC-T post M-alloHSCT and the incidence of CMV viremia. Methods We retrospectively reviewed all CMV and chimerism results of 47 patients for the first 6 months post M-alloHSCT. CDC-T was analyzed as a time-varying covariate for association with post M-alloHSCT CMV viremia. Results CMV viremia occurred in 15 (32%) and CDC-T was achieved in 38 (81%) recipients within the first 6 months post M-alloHSCT. On univariable analysis, increased CMV viremia was seen among patients with CDC-T (hazard ratio 2.81 [P = 0.07, 95% confidence interval = 0.93–8.52]). A 30-day landmark analysis showed that the incidence of CMV viremia at 6 months (regardless of recipient CMV serostatus) was 50% among those who had achieved CDC-T by day 30, and 23% among those who had not (P = 0.06). Conclusion We conclude that shorter time to CDC-T may be associated with higher risk of CMV viremia. If confirmed in a larger cohort, this might be a marker for risk stratification in the management of CMV in this population.

Risk factors and outcomes of cytomegalovirus viremia in cancer patients: A study from a medical center in northern Taiwan

Cytomegalovirus (CMV) is a pathogen and can cause life-threatening infection in the patients with malignancies. This study was conducted to investigate the risk factors and outcomes of CMV viremia in patients with malignancies. Data were collected with retrospective analysis from adults suffering from CMV viremia with underlying malignancies. A total of 107 patients were enrolled in a tertiary medical center in northern Taiwan from March 2008 to December 2009. Among the 107 patients who suffered with CMV viremia with an overall mortality rate of 56.1% (60/107), 75 patients (70.1%) had solid organ malignancies and 32 (29.9%) had hematological malignancies. Mechanical ventilation (p=0.048), leukocytosis (p=0.004), and lack of appropriate early treatment (p=0.011) were independent predisposing factors associated with higher mortality rate. CMV viremia predicts high mortality rate in cancer patients, especially in those with mechanical ventilation, leukocytosis, and lack of appropriate early treatment. Appropriate early antiviral therapy is recommended to improve outcomes.

Multi-Site PCR-Based CMV Viral Load Assessment-Assays Demonstrate Linearity and Precision, but Lack Numeric Standardization: A Report of the Association for Molecular Pathology

Viralload (VL) assessment of cytomegalovirus (CMV) by real-time PCR is an important tool for diagnosing and monitoring CMV viremia in patients with compromised immune systems. We report results from a sample exchange organized by members of the Association for Molecular Pathology that compared PCR results from 23 laboratories; 22 such laboratories used a laboratory-developed real-time PCR assay and one laboratory used a competitive PCR assay. The samples sent to each laboratory were comprised of a dilution panel of CMV virion-derived reference materials that ranged from 0 to 500,000 copies/ml. Accuracy, linearity, and intralaboratory precision were established for the different laboratory-developed assays. Overall, PCR results were linear for each laboratory (R(2) > 0.97 in all but two). While 13 laboratories showed no significant quantitative assay bias, 10 laboratories reported VLs that were significantly different compared with expected values (bias range, -0.82 to 1.4 logs). The intralaboratory precision [mean coefficient of variance of 2% to 5% (log-scale)] suggested that changes in VLs of less than 3- to fivefold may not be significantly different. There was no significant association between laboratory-specific technical variables (PCR platform, calibrator, extraction method) and assay linearity or accuracy. These data suggested that, within each laboratory, relative VL values were linear, but additional method standardization and a CMV DNA reference standard are needed to allow laboratories to achieve comparable numeric results.

Valganciclovir for treatment of cytomegalovirus viremia in patients following allogeneic hematopoietic stem cell transplantation

To investigate the efficacy and safety of valganciclovir in treatment of cytomegalovirus viremia in patients following allogeneic hematopoietic stem cell transplantation (allo-HSCT). Nineteen patients following allo-HSCT were diagnosed as with cytomegalovirus viremia with the CMV-DNA load of higher than 6.0 x 10(2) copies/ml confirmed by polymerase chain reaction (PCR) took orally valganciclovir at the dose of 900 mg bid for 14 days followed by 900 mg Qd for another 14 days. Since 4 weeks after the valganciclovir treatment PCR was conducted in the 6th, 8th, 12th, 16th, and 24th weeks later to detect the CMV-DNA level. CMV viremia was confirmed 40 days after HSCT on average with a median CMV-DNA load of 3.346 x 10(3) copies/ml. The total effective rate of valganciclovir was 94.7% (18/19). The CMV-DNA turned to negative in 7 d in 11 cases with a negative transfer rate of 54.7%, and in 14 d in 16 cases with a negative transfer rate of 84.2%. The median CMV DNA load reduction was 0.75 copies/ml and 0.084 log10 copies/ml/day. Severe adverse effects were not observed and CMV-related disease did not occur. Valganciclovir is an attractive and safe alternative for preemptive CMV viremia treatment in allo-HSCT recipients.

Once daily ganciclovir as initial pre-emptive therapy delayed until threshold CMV load ⩾10000 copies/ml: a safe and effective strategy for allogeneic stem cell transplant patients

Quantitative polymerase chain reaction (QPCR) for cytomegalovirus (CMV) is emerging as the preferred screening method for detection of CMV viremia in patients following allogeneic bone marrow and peripheral blood stem cell transplant. However, there are currently no universally accepted QPCR treatment thresholds at which to start pre-emptive therapy. We report here results of a pre-emptive therapy strategy using ganciclovir (GCV) 5 mg/kg initiated once daily (ODG) delayed till a threshold CMV load of > or =10 000 copies/ml whole blood in clinically stable patients. Sixty-nine at risk patients underwent allogeneic stem cell transplant. 48/69 (70%) patients had an initial episode of CMV viremia. 5/48 (10%) cleared viremia without requiring treatment. 28/43 (65%) patients requiring treatment initiated treatment with ODG. 17/28 (61%) patients successfully cleared CMV viremia on ODG, 10/28 (36%) patients required dose escalation to twice daily GCV for increasing viral loads. There were two cases of CMV disease (colitis) and no deaths due to CMV disease in patients initiating treatment with ODG. We conclude delaying pre-emptive therapy with ODG until whole blood QPCR> or =10 000 copies/ml is a safe and effective strategy for CMV viremia after allogeneic stem cell transplant in clinically stable patients.

Correlates of Change in Cytomegalovirus Viremia in Patients with Advanced Human Immunodeficiency Virus Infection Who Require Transfusion

The Viral Activation Transfusion Study compared leukocyte-reduced to unfiltered red blood cell transfusions in human immunodeficiency virus (HIV)- and cytomegalovirus (CMV)-coinfected patients. Relationships between serially measured plasma CMV load and clinical and laboratory outcomes over a median of 12 months were examined in 511 subjects. At baseline, subjects had a median of 15 CD4(+) cells/mm(3), 25% had CMV disease, and 21.5% were viremic. No relationship was found between changes in CMV viremia and changes in HIV RNA. Increased CMV viremia was associated with a concomitant fall in Karnofsky score. Highly active antiretroviral therapy (HAART) led to a decrease in CMV viremia after a 90-day delay. After adjustment for HIV load and CD4(+) cell count, CMV viremia remained associated with an increased risk of CMV disease (relative hazard, 5.78). In late-stage HIV-infected patients, CMV viremia was associated with lower functional status and increased risk of CMV disease. HAART suppressed CMV viremia only after a delay of several months.

Determination of the number of blood samples needed for optimal detection of cytomegalovirus viremia in immunocompromised patients using a shell-vial assay.

To establish the number of blood samples necessary for the diagnosis of viremic episodes caused by cytomegalovirus (CMV), a prospective analysis was conducted of 238 patients (38 renal transplant recipients and 200 HIV-infected patients) who developed CMV viremia. The usefulness of samples and the volume of blood required to demonstrate the presence of viremia by CMV was also studied. The first blood sample was diagnostic for CMV viremia in 53.3% of the viremic patients; the second sample documented an additional 22.2% of cases of viremia (75.5% of infected patients); and the third sample demonstrated viremia in the remaining 24.5%. Thus, a diagnosis of CMV viremia was established in every patient (100% of episodes of viremia). In this study, the use of three 3 ml blood samples collected at 24 h intervals was sufficient to detect all episodes of CMV viremia in patients clinically suspected to have disseminated disease.