valganciclovir and Neutropenia

Leukopenia and neutropenia (L/N) may affect treatment decisions, potentially resulting in poor clinical and economic outcomes among kidney transplant recipients (KTRs). The burden of L/N is poorly quantified systematically. This systematic literature review aimed to summarize the incidence of, risk factors for, and clinical and economic outcomes associated with L/N post-KT.. We systematically searched MEDLINE, Embase, and the Cochrane Library (from database inception-June 14, 2021) and conferences (past 3 years) to identify observational studies examining epidemiology, risk factors, or outcomes associated with L/N among adult KTRs.. Of 2081 records, 82 studies met inclusion criteria. Seventy-three studies reported the epidemiology of L/N post-KT. Pooled incidence of neutropenia, defined as absolute neutrophil counts (ANC) <1000/μl, ranged from 13% to 48% within 1-year post-transplant; ANC <500/μl ranged from 15% to 20%. Leukopenia, defined as white blood cell counts <3500/μl, was 19% to 83%. Eleven studies reported independent risk factors associated with L/N post-KT. D+/R- cytomegalovirus status, mycophenolic acid (MPA), and tacrolimus use were the most consistent risk factors across studies. Fourteen studies reported L/N-associated clinical outcomes. We noted a trend toward a positive association between neutropenia and acute rejection/opportunistic infections. Mixed findings were noted on the association between L/N and graft failure or mortality. Dosage modifications of valganciclovir, MPA, cotrimoxazole, and anti-thymoglobulin and the need for granulocyte colony-stimulating factor (G-CSF) use were common with L/N.. Findings suggest post-transplant L/N were common and associated with frequent modifications of immunosuppressive agents, requiring G-CSF use, and rejection or opportunistic infections. Findings highlight the need for interventions to reduce risk of L/N post-KT.

Topics: Adult; Anemia; Graft Rejection; Granulocyte Colony-Stimulating Factor; Humans; Immunosuppressive Agents; Kidney Transplantation; Leukopenia; Mycophenolic Acid; Neutropenia; Opportunistic Infections; Transplant Recipients; Valganciclovir

Cytomegalovirus (CMV) infection is the most common cause of congenital infection in the developed world, occurring in approximately 1% of all liveborns. Symptomatic disease occurs in 10% of all congenitally infected infants, resulting in a spectrum of clinical manifestations that include microcephaly, chorioretinitis, hepatosplenomegaly and sensorineural hearing loss, among others. Even those children who are asymptomatic at birth have a risk of hearing loss, with approximately 8% experiencing this sequela. Overall, congenital CMV infection accounts for one-third of all cases of sensorineural hearing loss. The economic burden of disease exceeds $2 billion annually in the USA. Therefore, this infection has been the target for antiviral therapy. Studies performed by the National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group (CASG) have evaluated ganciclovir for the treatment of symptomatic congenital CMV infection with central nervous system involvement. In a randomized, controlled clinical trial of ganciclovir treatment (6 mg/kg iv every 12 h for 6 weeks) brainstem-evoked responses were utilized as the primary endpoint and demonstrated stabilization of hearing both at 6 months and >1 year. Treatment was associated with neutropenia in over 60% of treated patients. Since ganciclovir must be given intravenously, studies with its prodrug, valganciclovir, have been performed to assess pharmacokinetics and pharmacodynamics. Currently, a clinical trial of 6 weeks versus 6 months of valganciclovir is being performed by the CASG. Notably, only intravenous ganciclovir and orally administered valganciclovir have been used to treat congenital CMV infection. Hopefully, other drugs such as maribavir will be available for evaluation in this population.

Topics: Antiviral Agents; Clinical Trials as Topic; Cytomegalovirus Infections; Ganciclovir; Hearing Loss, Central; Humans; Infant; Neutropenia; United States; Valganciclovir

Although cytomegalovirus (CMV) infection is an important factor in the pathogenesis of kidney allograft rejection, previous studies have not determined the optimal CMV prevention strategy to avoid indirect effects of the virus. In this randomized trial involving 140 kidney transplant recipients, incidence of acute rejection at 12 months was not lower with valganciclovir prophylaxis (for at least 3 months) compared with preemptive therapy initiated after detection of CMV DNA in whole blood. However, prophylaxis was associated with a lower risk of subclinical rejection at 3 months. Although both regimens were effective in preventing CMV disease, the incidence of CMV DNAemia (including episodes with higher viral loads) was significantly higher with preemptive therapy. Further research with long-term follow-up is warranted to better compare the two approaches.. The optimal regimen for preventing cytomegalovirus (CMV) infection in kidney transplant recipients, primarily in reducing indirect CMV effects, has not been defined.. This open-label, single-center, randomized clinical trial of valganciclovir prophylaxis versus preemptive therapy included kidney transplant recipients recruited between June 2013 and May 2018. After excluding CMV-seronegative recipients with transplants from seronegative donors, we randomized 140 participants 1:1 to receive valganciclovir prophylaxis (900 mg, daily for 3 or 6 months for CMV-seronegative recipients who received a kidney from a CMV-seropositive donor) or preemptive therapy (valganciclovir, 900 mg, twice daily) that was initiated after detection of CMV DNA in whole blood (≥1000 IU/ml) and stopped after two consecutive negative tests (preemptive therapy patients received weekly CMV PCR tests for 4 months). The primary outcome was the incidence of biopsy-confirmed acute rejection at 12 months. Key secondary outcomes included subclinical rejection, CMV disease and DNAemia, and neutropenia.. The incidence of acute rejection was lower with valganciclovir prophylaxis than with preemptive therapy (13%, 9/70 versus 23%, 16/70), but the difference was not statistically significant. Subclinical rejection at 3 months was lower in the prophylaxis group (13% versus 29%, P = 0.027). Both regimens prevented CMV disease (in 4% of patients in both groups). Compared with prophylaxis, preemptive therapy resulted in significantly higher rates of CMV DNAemia (44% versus 75%, P < 0.001) and a higher proportion of patients experiencing episodes with higher viral load (≥2000 IU/ml), but significantly lower valganciclovir exposure and neutropenia.. Among kidney transplant recipients, the use of valganciclovir prophylaxis did not result in a significantly lower incidence of acute rejection compared with the use of preemptive therapy.. Optimizing Valganciclovir Efficacy in Renal Transplantation (OVERT Study), ACTRN12613000554763 .

Topics: Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; Humans; Kidney Transplantation; Neutropenia; Transplant Recipients; Valganciclovir

Maribavir is a benzimidazole riboside with activity against cytomegalovirus (CMV). The safety and efficacy of maribavir for preemptive treatment of CMV infection in transplant recipients is not known.. In a phase 2, open-label, maribavir dose-blinded trial, recipients of hematopoietic-cell or solid-organ transplants (≥18 years of age, with CMV reactivation [1000 to 100,000 DNA copies per milliliter]) were randomly assigned to receive maribavir at a dose of 400, 800, or 1200 mg twice daily or the standard dose of valganciclovir for no more than 12 weeks. The primary efficacy end point was the percentage of patients with a response to treatment, defined as confirmed undetectable CMV DNA in plasma, within 3 weeks and 6 weeks after the start of treatment. The primary safety end point was the incidence of adverse events that occurred or worsened during treatment.. Of the 161 patients who underwent randomization, 159 received treatment, and 156 had postbaseline data available - 117 in the maribavir group and 39 in the valganciclovir group. The percentage of patients with postbaseline data available who had a response to treatment within 3 weeks was 62% among those who received maribavir and 56% among those who received valganciclovir. Within 6 weeks, 79% and 67% of patients, respectively, had a response (risk ratio, 1.20; 95% confidence interval, 0.95 to 1.51). The percentages of patients with a response to treatment were similar among the maribavir dose groups. Two patients who had a response to treatment had a recurrence of CMV infection within 6 weeks after starting maribavir at a dose of 800 mg twice daily; T409M resistance mutations in CMV UL97 protein kinase developed in both patients. The incidence of serious adverse events that occurred or worsened during treatment was higher in the maribavir group than in the valganciclovir group (52 of 119 patients [44%] vs. 13 of 40 [32%]). A greater percentage of patients in the maribavir group discontinued the trial medication because of an adverse event (27 of 119 [23%] vs. 5 of 40 [12%]). A higher incidence of gastrointestinal adverse events was reported with maribavir, and a higher incidence of neutropenia was reported with valganciclovir.. Maribavir at a dose of at least 400 mg twice daily had efficacy similar to that of valganciclovir for clearing CMV viremia among recipients of hematopoietic-cell or solid-organ transplants. A higher incidence of gastrointestinal adverse events - notably dysgeusia - and a lower incidence of neutropenia were found in the maribavir group. (Funded by ViroPharma/Shire Development; EudraCT number, 2010-024247-32.).

Topics: Adult; Aged; Allografts; Antiviral Agents; Benzimidazoles; Cytomegalovirus; Cytomegalovirus Infections; Dysgeusia; Female; Gastrointestinal Diseases; Hematopoietic Stem Cell Transplantation; Humans; Intention to Treat Analysis; Male; Middle Aged; Neutropenia; Organ Transplantation; Ribonucleosides; Valganciclovir; Viremia; Virus Activation

Treatment of solid-organ transplant (SOT) patients with ganciclovir (GCV)-valganciclovir (VGCV) according to the manufacturer's recommendations may result in over- or underexposure. Bayesian prediction based on a population pharmacokinetics model may optimize GCV-VGCV dosing, achieving the area under the curve (AUC) therapeutic target. We conducted a two-arm, randomized, open-label, 40% superiority trial in adult SOT patients receiving GCV-VGCV as prophylaxis or treatment of cytomegalovirus infection. Group A was treated according to the manufacturer's recommendations. For group B, the dosing was adjusted based on target exposures using a Bayesian prediction model (NONMEM). Fifty-three patients were recruited (27 in group A and 26 in group B). About 88.6% of patients in group B and 22.2% in group A reached target AUC, achieving the 40% superiority margin (P< 0.001; 95% confidence interval [CI] difference, 47 to 86%). The time to reach target AUC was significantly longer in group A than in group B (55.9 ± 8.2 versus 15.8 ± 2.3 days,P< 0.001). A shorter time to viral clearance was observed in group B than in group A (12.5 versus 17.6 days;P= 0.125). The incidences of relapse (group A, 66.67%, and group B, 9.01%) and late-onset infection (group A, 36.7%, and group B, 7.7%) were higher in group A. Neutropenia and anemia were related to GCV overexposure. GCV-VCGV dose adjustment based on a population pharmacokinetics Bayesian prediction model optimizes GCV-VGCV exposure. (This study has been registered at ClinicalTrials.gov under registration no. NCT01446445.).

Topics: Adult; Aged; Anemia; Antiviral Agents; Area Under Curve; Bayes Theorem; Cytomegalovirus; Cytomegalovirus Infections; Drug Combinations; Drug Dosage Calculations; Female; Ganciclovir; Heart Transplantation; Humans; Kidney Transplantation; Liver Transplantation; Male; Middle Aged; Neutropenia; Recurrence; Valganciclovir; Viral Load

Optimal prevention of late cytomegalovirus (CMV) disease is poorly defined.. To compare valganciclovir prophylaxis with polymerase chain reaction-guided preemptive therapy.. Randomized, double-blind trial. (ClinicalTrials.gov: NCT00016068).. Multicenter trial.. 184 recipients of hematopoietic cell transplantation (HCT) who were at high risk for late CMV disease (95 patients received valganciclovir and 89 received placebo).. 6 months of valganciclovir (900 mg/d) or placebo. Patients with polymerase chain reaction positivity at 1000 copies/mL or greater or a 5-fold increase over baseline were treated with ganciclovir or valganciclovir (5 mg/kg or 900 mg twice daily, respectively).. The composite primary end point was death, CMV disease, or other invasive infections by 270 days after HCT. Secondary end points were CMV disease, CMV DNAemia, death, other infections, resource utilization, ganciclovir resistance, quality of life, immune reconstitution, and safety.. The primary composite outcome occurred in 20% of valganciclovir recipients versus 21% of placebo-preemptive therapy recipients (treatment difference, -0.01 [95% CI, -0.13 to 0.10]; P = 0.86). There was no difference in the primary end point or its components 640 days after HCT. The incidence of a CMV DNAemia level of 1000 copies/mL or greater or a 5-fold increase over baseline was reduced in the valganciclovir group (11% vs. 36%; P < 0.001). Neutropenia was not significantly different at the absolute neutrophil count of less than 0.5 × 109 cells/L (P = 0.57); however, more patients received hematopoietic growth factors in the valganciclovir group (25.3% vs. 12.4%; P = 0.026). No significant differences were seen in other secondary outcomes.. Some high-risk patients were not included.. Valganciclovir prophylaxis was not superior in reducing the composite end point of CMV disease, invasive bacterial or fungal disease, or death when compared with polymerase chain reaction-guided preemptive therapy. Both strategies performed similarly with regard to most clinical outcomes.. Roche Laboratories.

Topics: Adolescent; Adult; Aged; Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; DNA, Viral; Double-Blind Method; Female; Follow-Up Studies; Ganciclovir; Hematopoietic Stem Cell Transplantation; Humans; Immunity, Cellular; Male; Middle Aged; Neutropenia; Polymerase Chain Reaction; Quality of Life; Treatment Outcome; Valganciclovir; Young Adult

The treatment of symptomatic congenital cytomegalovirus (CMV) disease with intravenous ganciclovir for 6 weeks has been shown to improve audiologic outcomes at 6 months, but the benefits wane over time.. We conducted a randomized, placebo-controlled trial of valganciclovir therapy in neonates with symptomatic congenital CMV disease, comparing 6 months of therapy with 6 weeks of therapy. The primary end point was the change in hearing in the better ear ("best-ear" hearing) from baseline to 6 months. Secondary end points included the change in hearing from baseline to follow-up at 12 and 24 months and neurodevelopmental outcomes, with each end point adjusted for central nervous system involvement at baseline.. A total of 96 neonates underwent randomization, of whom 86 had follow-up data at 6 months that could be evaluated. Best-ear hearing at 6 months was similar in the 6-month group and the 6-week group (2 and 3 participants, respectively, had improvement; 36 and 37 had no change; and 5 and 3 had worsening; P=0.41). Total-ear hearing (hearing in one or both ears that could be evaluated) was more likely to be improved or to remain normal at 12 months in the 6-month group than in the 6-week group (73% vs. 57%, P=0.01). The benefit in total-ear hearing was maintained at 24 months (77% vs. 64%, P=0.04). At 24 months, the 6-month group, as compared with the 6-week group, had better neurodevelopmental scores on the Bayley Scales of Infant and Toddler Development, third edition, on the language-composite component (P=0.004) and on the receptive-communication scale (P=0.003). Grade 3 or 4 neutropenia occurred in 19% of the participants during the first 6 weeks. During the next 4.5 months of the study, grade 3 or 4 neutropenia occurred in 21% of the participants in the 6-month group and in 27% of those in the 6-week group (P=0.64).. Treating symptomatic congenital CMV disease with valganciclovir for 6 months, as compared with 6 weeks, did not improve hearing in the short term but appeared to improve hearing and developmental outcomes modestly in the longer term. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT00466817.).

Topics: Antiviral Agents; Audiometry; Child Development; Cytomegalovirus Infections; Double-Blind Method; Drug Administration Schedule; Evoked Potentials, Auditory, Brain Stem; Ganciclovir; Gestational Age; Hearing Loss, Sensorineural; Humans; Infant, Newborn; Neutropenia; Valganciclovir

Cytomegalovirus (CMV) infection is a major infectious complication post-allogeneic hematopoietic stem cell transplantation (HSCT). CMV seropositivity in Eastern Mediterranean and certain Asian countries is reported to be close to 100%; hence, the need for effective pre-emptive treatment strategy that has low toxicity. Valganciclovir (VGC) is a prodrug of ganciclovir with high bioavailability.. HSCT patients with documented CMV infection (as defined by positive CMV antigenemia) were treated as outpatients with VGC at a starting dose of 900 mg twice daily for 1 week. Those who were antigenemia negative after one week received 900 mg once daily for another week and treatment was subsequently discontinued. Those who were positive after one week of therapy continued on the twice-daily treatment schedule for another week and changed to a daily schedule once they converted to antigenemia negativity.. From January 2004 to December 2007, 47 HSCT patients received preemptive treatment with VGC for 61 episodes of CMV infection. The antigenemia range was 1 to 700 infected cells/slide. Complete responses were observed in 92% and 97% after the 1st and 2nd week of treatment, respectively. Three percent of the episodes were considered refractory, requiring alternative therapy. No CMV disease was observed in this cohort.. Neutropenia was the main observed toxicity, requiring granulocyte-colony stimulating factor in 8 episodes. Outpatient treatment of CMV infection with "short-course oral VGC" given as a one-week twice-daily treatment and one week once daily maintenance is a highly effective therapy with minimal toxicity. These results require validation in a larger, randomized study.

Topics: Administration, Oral; Adolescent; Adult; Antigens, Viral; Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; Drug Administration Schedule; Female; Ganciclovir; Hematopoietic Stem Cell Transplantation; Humans; Kidney Diseases; Male; Middle Aged; Neutropenia; Treatment Outcome; Valganciclovir; Young Adult

Cytomegalovirus (CMV) is a common infection in abdominal transplant recipients (ATR). Prevention of CMV in the highest risk population (CMV IgG donor+/recipient-) is critical as CMV is associated with negative outcomes. Guideline recommended prophylactic valganciclovir dosing is 900 mg daily for 6 months in this population. However, reduced dosing strategies are utilized in practice.. This single center, retrospective study in adult ATR compared full valganciclovir prophylactic dosing (900 mg daily for 6 months) to reduced dosing (900 mg daily for 3 months, then 450 mg daily for 3 months). The primary endpoint was incidence of CMV infection with viral load >1000 IU/mL. Secondary endpoints included incidence of CMV infection with viral load 200-1000 IU/mL, neutropenia, and leukopenia.. Incidence of CMV infection with viral load >1000 IU/mL (29% vs. 27%, p = 1) or CMV infection with viral load 200-1000 IU/mL (6% vs. 12%, p = .421) did not differ significantly between 68 ATR in reduced and full dosing groups, as well as incidence of leukopenia (94% vs. 97%, p = 1) and neutropenia (77% vs. 70%, p = .586).. There was no difference in the incidence of CMV infection, neutropenia, or leukopenia of the two dosing regimens, although time to CMV diagnosis was different.

Topics: Adult; Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; Ganciclovir; Humans; Neutropenia; Retrospective Studies; Transplant Recipients; Valganciclovir

Valganciclovir for 200 days is standard care for cytomegalovirus (CMV) prophylaxis in high-risk CMV-seronegative kidney transplant recipients who receive an organ from a CMV-seropositive donor, but its use is limited by myelosuppression.. To compare the efficacy and safety of letermovir with valganciclovir for prevention of CMV disease in CMV-seronegative kidney transplant recipients who receive an organ from a CMV-seropositive donor.. Randomized, double-masked, double-dummy, noninferiority, phase 3 trial in adult CMV-seronegative kidney transplant recipients who received an organ from a CMV-seropositive donor at 94 participating sites between May 2018 and April 2021 (final follow-up in April 2022).. Participants were randomized in a 1:1 ratio (stratified by receipt of lymphocyte-depleting induction immunosuppression) to receive letermovir, 480 mg, orally daily (with acyclovir) or valganciclovir, 900 mg, orally daily (adjusted for kidney function) for up to 200 days after transplant, with matching placebos.. The primary outcome was CMV disease, confirmed by an independent masked adjudication committee, through posttransplant week 52 (prespecified noninferiority margin, 10%). CMV disease through week 28 and time to onset of CMV disease through week 52 were secondary outcomes. Exploratory outcomes included quantifiable CMV DNAemia and resistance. The rate of leukopenia or neutropenia through week 28 was a prespecified safety outcome.. Among 601 participants randomized, 589 received at least 1 dose of the study drug (mean age, 49.6 years; 422 [71.6%] men). Letermovir (n = 289) was noninferior to valganciclovir (n = 297) for prevention of CMV disease through week 52 (10.4% vs 11.8% of participants with committee-confirmed CMV disease; stratum-adjusted difference -1.4% [95% CI, -6.5% to 3.8%]). No participants who received letermovir vs 5 participants (1.7%) who received valganciclovir developed CMV disease through week 28. Time to onset of CMV disease was comparable between the groups (hazard ratio, 0.90 [95% CI, 0.56-1.47]). Quantifiable CMV DNAemia was detected in 2.1% of participants in the letermovir group vs 8.8% in the valganciclovir group by week 28. Of participants evaluated for suspected CMV disease or CMV DNAemia, none (0/52) who received letermovir and 12.1% (8/66) who received valganciclovir had resistance-associated substitutions. The rate of leukopenia or neutropenia through week 28 was lower with letermovir vs valganciclovir (26% vs 64%; difference, -37.9% [95% CI, -45.1% to -30.3%]; P < .001). Fewer participants in the letermovir group than the valganciclovir group discontinued prophylaxis due to adverse events (4.1% vs 13.5%) or drug-related adverse events (2.7% vs 8.8%).. Among adult CMV-seronegative kidney transplant recipients who received an organ from a CMV-seropositive donor, letermovir was noninferior to valganciclovir for prophylaxis of CMV disease over 52 weeks, with lower rates of leukopenia or neutropenia, supporting its use for this indication.. ClinicalTrials.gov Identifier: NCT03443869; EudraCT: 2017-001055-30.

Topics: Adult; Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; Female; Humans; Kidney Transplantation; Male; Middle Aged; Neutropenia; Valganciclovir

Optimal dosing of valganciclovir (VGCV) for cytomegalovirus (CMV) prevention in pediatric solid organ transplantation recipients (SOTR) is controversial. Dosing calculated based on body surface area (BSA) and creatinine clearance is recommended but simplified body weight (BW) dosing is often prescribed. We conducted a retrospective 6-center study to compare safety and efficacy of these strategies in the first-year posttransplant There were 100 (24.2%) pediatric SOTR treated with BSA and 312 (75.7%) with BW dosing. CMV DNAemia was documented in 31.0% vs 23.4% (P = .1) at any time during the first year and breakthrough DNAemia in 16% vs 12.2% (P = .3) of pediatric SOTR receiving BSA vs BW dosing, respectively. However, neutropenia (50% vs 29.3%, P <.001), lymphopenia (51% vs 15.0%, P <.001), and acute kidney injury causing treatment modification (8.0% vs 1.8%, P <.001) were documented more frequently during prophylaxis in pediatric SOTR receiving BSA vs BW dosing. The adjusted odds ratio of VGCV-attributed toxicities comparing BSA and BW dosing was 2.3 (95% confidence interval [CI], 1.4-3.7] for neutropenia, 7.0 (95% CI, 3.9-12.4) for lymphopenia, and 4.6 (95% CI, 2.2-9.3) for premature discontinuation or dose reduction of VGCV, respectively. Results demonstrate that BW dosing is associated with significantly less toxicity without any increase in CMV DNAemia.

Topics: Antiviral Agents; Body Surface Area; Body Weight; Child; Cytomegalovirus; Cytomegalovirus Infections; Ganciclovir; Humans; Lymphopenia; Neutropenia; Organ Transplantation; Retrospective Studies; Valganciclovir

Limited data exist on the incidence and clinical outcomes of neutropenia among kidney transplant recipients. Our study included 572 adults who received a kidney transplant at the University of California, San Francisco Medical Center between 2012 and 2018, and were CMV-mismatched or had a PRA ≥ 80%. Recipients with HIV, Hepatitis B and C, and primary non-function were excluded. Participants were followed for at least 1 year after transplantation. Neutropenia was defined as absolute neutrophil count < 1000 cells/μl. Cox proportional hazards regression models using neutropenia as a time-varying predictor were used to determine the risk of mycophenolic acid and valganciclovir changes, rejection, hospitalizations and use of granulocyte colony stimulating factor. Models were adjusted for demographics and transplant characteristics. Mean follow-up was 3.7 (SD, 1.8) years. The mean age of the cohort was 50.4 (13.1) years, and 57.5% were female. A total of 208 (36.3%) participants had neutropenia. Neutropenia was associated with an increased risk of valganciclovir or MPA dose reductions or discontinuations [adjusted hazard ratio, aHR: 7.78, 95% CI: 4.73-12.81], rejection [aHR 2.00, 95% CI: 1.10-3.64] and hospitalizations [aHR 3.32, 95% CI: 2.12-5.19]. Neutropenia occurs frequently after kidney transplantation and leads to more medication changes and adverse clinical outcomes.

Topics: Adult; Cytomegalovirus Infections; Female; Graft Rejection; Humans; Kidney Transplantation; Middle Aged; Neutropenia; Retrospective Studies; Transplant Recipients; Valganciclovir

The aim of this study was to investigate whether low-dose valganciclovir (VGCV) prophylaxis for cytomegalovirus (CMV) infection increased the risk of developing neutropenia in heart transplant recipients (HTRs). Forty-three HTRs receiving VGCV were divided into two groups: those who received VGCV prophylaxis (n = 22) and those who did not (n = 21). Neutropenia was defined as an absolute neutrophil count ˂1500/µL and was monitored for approximately one year post-transplantation. In the prophylaxis group, 77.3% (17/22) of HTRs experienced neutropenia, which was significantly higher than that in the no prophylaxis group (42.9% [9/21], p = 0.031). No significant differences in the duration of VGCV administration and cumulative dose up to the first neutropenia episode were observed between the groups. Meanwhile, the cumulative dose of mycophenolate mofetil was significantly higher in the prophylaxis group than in the no prophylaxis group (p = 0.018); the daily maintenance dose and regularly measured area under the concentration-time curve (AUC) of mycophenolic acid did not significantly differ between groups. In conclusion, the risk of developing neutropenia was higher in HTRs receiving low-dose VGCV prophylaxis than it was in those not receiving prophylaxis, probably not attributed to dosing period and cumulative dose of VGCV until the onset of neutropenia.

Topics: Antiviral Agents; Ganciclovir; Heart Transplantation; Humans; Neutropenia; Risk Assessment; Valganciclovir

Prophylaxis with valganciclovir (VGCV) is used routinely to prevent cytomegalovirus (CMV) infections in at-risk pediatric solid organ transplant (SOT) recipients. However, the rate and factors associated with toxicities in this population are not well-described. We conducted a retrospective cohort study of children undergoing SOT at our hospital from January 2012-June 2018. We evaluated the frequency of hematologic and renal toxicities from day 15 through 1-year post-SOT in relation to antiviral exposures, focused on VGCV prophylaxis. Marginal rate models were used to determine the risk of kidney injury and neutropenia in relation to VGCV prophylaxis. Among 281 SOTs, VGCV prophylaxis was administered on 20.1% of all follow-up days. The incidence rates of kidney injury, leukopenia, and neutropenia were significantly higher during VGCV prophylaxis compared to when no antiviral agents were given. Using multivariable marginal rate models, receipt of VGCV prophylaxis was associated with development of kidney injury (rate ratio [RR] 1.79, 95% confidence interval [CI]: 1.22-2.65) and neutropenia (RR 4.82, 95% CI: 3.08-7.55). VGCV dosing did not impact the development of kidney injury or neutropenia. Toxicities are common with VGCV prophylaxis in pediatric SOT recipients.

Topics: Antiviral Agents; Child; Cytomegalovirus Infections; Ganciclovir; Humans; Kidney Transplantation; Neutropenia; Retrospective Studies; Transplant Recipients; Valganciclovir

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 10 days after KTx and continued for 200 days. 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 450 mg 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.

Topics: Adolescent; Anemia; Antibodies, Viral; Antiviral Agents; Child; Child, Preschool; Cytomegalovirus; Cytomegalovirus Infections; Digestive System Diseases; Female; Humans; Kidney Transplantation; Male; Neutropenia; Retrospective Studies; Valganciclovir; Young Adult

Immunosuppressive drugs are necessary to avoid or reduce the risk of rejection of transplanted organs. The immunosuppression generated may result in these patients needing  antibiotics and antivirals to be prescribed to them in conjunction with their immunosuppressants to avoid the risk of infection. This has generated an increase in neutropenia in patients treated with mycophenolate mofetil in combination with valganciclovir. The purpose of this study is to estimate the risk of neutropenia attributable to combination treatment of mycophenolate mofetil with valganciclovir in patients with a transplanted liver.. This is a retrospective cohort study. It included patients who received a liver transplant between 2012 and 2017 and who were treated with mycophenolate mofetil or with a combination of mycophenolate mofetil and valganciclovir. Minimum follow-up was 100 days posttransplantation. Children under 16 years of age and patients who died during follow-up were excluded. Binary logistic regression analysis was used to determine the association of neutropenia with sex, age, diabetes, creatinine at baseline and at discharge, and concomitant treatment of mycophenolate mofetil with valganciclovir. Relative risk and 95% CI were calculated using logistic regression coefficients.. 144 patients were analyzed, 87 were treated with mycophenolate mofetil and 57 received mycophenolate mofetil and valganciclovir together. An overall risk of neutropenia of 37% [95% CI (29- 45)] was observed. The risk was significantly higher in patients who received the combination of mycophenolate mofetil and valganciclovir (56%) than in those treated with mycophenolate mofetil alone (24%), p = 0.001. Binarylogistic-regression analysis revealed that concomitant use of mycophenolate mofetil with valganciclovir was associated with an increased risk of neutropenia: Relative risk = 4.97, 95% CI [2.25-11.00].. Our study shows that concomitant use of mycophenolate mofetil and valganciclovir increases the risk of neutropenia in patients with a transplanted liver.. Objetivo: Los fármacos inmunosupresores son necesarios para evitar o reducir el riesgo de rechazo de órganos trasplantados. La inmunosupresión generada puede dar lugar a que estos pacientes necesiten recibir antibióticos y antivíricos con los inmunosupresores para evitar el riesgo de infecciones. Esto ha generado un incremento de neutropenia en pacientes tratados conjuntamente con micofenolato de mofetilo y valganciclovir. El objetivo de este estudio es estimar el riesgo de neutropenia atribuible al tratamiento concomitante de micofenolato de ofetilo y valganciclovir en pacientes trasplantados hepáticos.Método: Estudio de cohorte retrospectiva. Se incluyeron pacientes receptores de hígado entre 2012 y 2017 tratados con micofenolato de mofetilo o con la combinación de micofenolato de mofetilo y valganciclovir, con al menos 100 días de seguimiento postrasplante. Se excluyeron menores de 16 años y pacientes fallecidos durante el seguimiento. El análisis de regresión logística binaria se utilizó para determinar la asociación del riesgo de neutropenia con el sexo, edad, diabetes, creatinina basal y al alta, y tratamiento concomitante de micofenolato de mofetilo y valganciclovir. El riesgo relativo y los IC 95% se calcularon mediante los coeficientes de regresión logística.Resultados: Un total de 144 pacientes fueron analizados, 87 se trataron con micofenolato de mofetilo y 57 recibieron conjuntamente micofenolato de mofetilo y valganciclovir, observándose un riesgo de neutropenia del 37%, IC 95% [29-45]. Este riesgo fue significativamente mayor en pacientes que recibieron la combinación de micofenolato de mofetilo y valganciclovir (56%) respecto a los tratados solo con micofenolato de mofetilo (24%), p = 0,001. El análisis de regresión logística binaria reveló que el uso concomitante de micofenolato de mofetilo y valganciclovir se asociaba a un mayor riesgo de neutropenia: riesgo relativo = 4,97, IC 95% [2,25-11,00].Conclusiones: Nuestro estudio demuestra que el uso concomitante de micofenolato de mofetilo y valganciclovir aumenta el riesgo de neutropenia en pacientes trasplantados hepáticos.

Topics: Child; Humans; Immunosuppressive Agents; Liver Transplantation; Mycophenolic Acid; Neutropenia; Retrospective Studies; Valganciclovir

Valganciclovir (2/d) therapy for 6 months in neonates with symptomatic congenital cytomegalovirus (cCMV) infection improves hearing and neurodevelopmental outcome. The only reported adverse event was neutropenia. Since 2009, our protocol for symptomatic cCMV infection was a 1-year treatment of 2/d for the first 3 months followed by 9 months of 1/d.. A retrospective study. Infants with cCMV treated with valganciclovir for 1 year were recruited. Data of drug-related hematologic adverse events were collected.. One hundred sixty infants were eligible; 46 (28.8%) had experienced at least 1 episode of neutropenia (58 episodes), the majority (39/46, 84.8%) during the first 3 months of treatment and 7 (15.2%) during the last 9 months of treatment. Grades 3 and 4 neutropenia occurred in 9 (5.6%) children, almost exclusively during the first 3 months of treatment. Anemia (hemoglobin <9 g/dL) was recorded in 12 (7.5%) children during the first 3 months of 2/d treatment. Four children presented with hemoglobin levels <7 g/dL and needed a blood transfusion. One child was diagnosed with transient pure red cell aplasia. No long-term adverse events were recorded.. Although prolonged valganciclovir treatment for cCMV is safe, a close monitoring of the white blood cell count and hemoglobin levels is warranted. Much lower rates of grades 3 and 4 neutropenia were observed than previously reported, probably owing to our unique treatment protocol. Nevertheless, drug-induced anemia should be of primary concern. The optimal protocol assessing clinical outcome, concurrently with potential side effects, has not yet been determined.

Topics: Anemia; Antiviral Agents; Cytomegalovirus Infections; Drug-Related Side Effects and Adverse Reactions; Female; Follow-Up Studies; Humans; Infant; Male; Neutropenia; Retrospective Studies; Valganciclovir

Topics: Antiviral Agents; Cytomegalovirus Infections; Ganciclovir; Humans; Neutropenia; Valganciclovir

Topics: Anti-Bacterial Agents; Antiviral Agents; Coinfection; Cytomegalovirus Infections; Female; Ganciclovir; Heart Failure; Heart Transplantation; Humans; Immunocompromised Host; Immunosuppressive Agents; Middle Aged; Neutropenia; Pneumonia, Bacterial; Pneumonia, Viral; Postoperative Complications; Preoperative Care; Pseudomonas aeruginosa; Shock, Septic; Tomography, X-Ray Computed; Valganciclovir

This study evaluated the efficacy of prophylactic ValGCV in preventing CMV and EBV infections in a single-center pediatric kidney transplant population (2008-2014). Therapy duration was determined according to donor/recipient serostatus. EBV monitoring was performed using monthly plasma PCR for 18 months post-transplant and for CMV, monthly for 6 months after prophylaxis cessation. Data were collected on 35 children, median age 10.6 years. There were 15 (42.9%) and 11 (31.4%) recipients seronegative for CMV or EBV, respectively, who received a kidney from a seropositive donor. Prophylaxis was ceased by 6 months in 24 (69%), between seven and 13 months in 10 (29%) children. Fourteen (40%) and eight (23%) children experienced CMV and EBV DNAemia, respectively. Ten of the 14 (71%) episodes of CMV DNAemia occurred in the first 6 months following cessation of prophylaxis. Shorter prophylaxis was associated with increased CMV DNAemia (P = 0.044). There was an inverse correlation between adjusted ValGCV dose and EBV incidence/timing. Neutropenia was more common if ValGCV dosage was ≥10% of the dose predicted (by BSA and creatinine clearance). ValGCV prevents CMV and may modify EBV infection risk. Frequent dosing adjustment for BSA and creatinine clearance is required to optimize safety and efficacy.

Topics: Adolescent; Antiviral Agents; Child; Child, Preschool; Cytomegalovirus; Cytomegalovirus Infections; Epstein-Barr Virus Infections; Female; Ganciclovir; Glomerular Filtration Rate; Graft Rejection; Graft Survival; Herpesvirus 4, Human; Humans; Immunosuppressive Agents; Infant; Kidney Transplantation; Male; Neutropenia; Polymerase Chain Reaction; Retrospective Studies; RNA, Viral; Tissue Donors; Valganciclovir

Pre-emptive therapy with valganciclovir (VGCV) has become the standard therapy for preventing cytomegalovirus (CMV) infection after allogeneic hematopoietic stem cell transplantation (HSCT). The effectiveness of low-dose VGCV (900 mg per day) has been shown to be equal to that of standard-dose VGCV (900 mg twice daily); however, individualized optimal dosing and toxicity of VGCV have not been reported.. We conducted a retrospective study to evaluate the optimal dose of VGCV as pre-emptive therapy for preventing CMV infection by comparing the frequency of adverse events (AEs) and clinical efficacy in a low-dose VGCV group with those in a standard-dose VGCV group. Thirty-eight patients who were administered VGCV because of CMV antigenemia after HSCT were analyzed.. Neutropenia (standard-dose group: 33%, low-dose group: 15%, P = 0.26) and thrombocytopenia (standard-dose group: 39%, low-dose group: 15%, P = 0.14) were frequent AEs of VGCV, and a significantly higher frequency of overall AEs was detected in the standard-dose group than in the low-dose group (P < 0.01). In comparison of dosage based on weight, dosage of VGCV >27 mg/kg was closely related to onset of AEs (P = 0.04).. Low-dose VGCV was not inferior in clinical efficacy, including clearance rate of CMV antigenemia and incidence of consequent CMV disease, to standard-dose VGCV as was previously reported. Initial low-dose VGCV for pre-emptive CMV therapy markedly reduces hematologic toxicity and has clinical efficacy equivalent to that of standard-dose VGCV. It is therefore reasonable for patients, except for noticeably overweight patients, to be given initial low-dose VGCV.

Topics: Antiviral Agents; Cytomegalovirus Infections; Dose-Response Relationship, Drug; Ganciclovir; Humans; Neutropenia; Stem Cell Transplantation; Thrombocytopenia; Valganciclovir

Neutropenia after kidney transplant is an adverse event usually treated with a dosage reduction of mycophenolic acid. We evaluated the efficacy and safety of substituting mycophenolic acid with everolimus in patients with persistent neutropenia after kidney transplant.. This study was a retrospective analysis. A total of 17 patients who were initially treated with mycophenolic acid (1912 ± 196 mg/d), calcineurin inhibitors, and methylprednisolone for kidney transplant were included.. In 15 patients, neutropenia occurred within the first 3 months (during valganciclovir administration), and in 2 patients between the fourth and sixth month after transplant. One hundred eighteen episodes of neutropenia were recorded, originally treated by reducing the dosage of mycophenolic acid (765 ± 390 mg/d) and administering granulocyte colony-stimulating factor. Three patients experienced acute rejection 5 to 10 days after reducing the dosage of mycophenolic acid, and they were successfully treated with pulse steroids. Five patients developed cytomegalovirus infection 108 ± 65 days after the onset of neutropenia. After replacing mycophenolic acid with everolimus, episodes of neutropenia were observed in 6 patients. In 1 patient, discontinuing everolimus was necessary after 1.5 months of treatment. In 5 patients with cytomegalovirus infection, neutropenia subsided after termination of valganciclovir treatment. In the remaining 11 patients, no episodes of neutropenia were observed. No episodes of acute rejection occurred, and renal function remained stable during a followup of 47 ± 30 months (estimated glomerular filtration rate [eGFRMDRD6]: 45 ± 14 mL/min/1.73 m2→47 ± 22 mL/min/1.73 m2].. Replacing mycophenolic acid with everolimus appears to be a safe and effective alternative treatment in neutropenic renal transplant recipients.

Topics: Adult; Cytomegalovirus Infections; Drug Substitution; Drug Therapy, Combination; Everolimus; Female; Ganciclovir; Graft Rejection; Graft Survival; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid; Neutropenia; Retrospective Studies; Risk Factors; Sirolimus; Steroids; Time Factors; Treatment Outcome; Valganciclovir

The most frequent adverse events associated with valganciclovir treatment are hematological disturbances such as neutropenia. However, the consequences of neutropenia are unknown. We investigated the clinical impact of neutropenia during CMV preemptive therapy and its relationship with the length of antiviral therapy.. An observational, prospective cohort of 67 solid organ transplant recipients receiving CMV preemptive therapy was studied.. Severe neutropenia occurred in 21.8% of the patients at a median of three weeks after initiating antiviral therapy. No association was observed between neutropenia and infection risk in these patients. Liver transplant recipients had 6.7 fold increased risk of neutropenia during CMV therapy compared to kidney transplant recipients (p = 0.012). Patients who developed severe neutropenia received antiviral therapy a median of six days longer than patient who did not (p = 0.457).. Despite the frequency of neutropenia during CMV preemptive therapy, the incidence of infections is not increased. Adjusting the length of preemptive therapy during the episodes of viremia may be recommended, especially in patients with concurrent risk factors for neutropenia such as liver recipients. Further trials are warranted to confirm the safety of this approach.

Topics: Antiviral Agents; Bacterial Infections; Cytomegalovirus Infections; Female; Ganciclovir; Humans; Kidney Transplantation; Liver Transplantation; Male; Middle Aged; Neutropenia; Risk Factors; Transplant Recipients; Valganciclovir

Cytomegalovirus (CMV) is a major cause of morbidity and mortality following solid organ transplantation (SOT). Two strategies, prophylactic, and preemptive have emerged for the prevention of CMV infection and disease after SOT. This retrospective chart review of two liver transplant cohorts: prophylactic and preemptive, compares the clinical impact of transitioning from prophylactic to preemptive strategy. The primary outcome is the incidence of CMV viremia at 3-and 6-months post-transplant. Secondary outcomes include: incidence of CMV tissue-invasive disease, acute cellular rejection, leukopenia and neutropenia, opportunistic infection rates, hospital readmission rates, and mortality at 3-and 6-months post-transplant. A total of 109 patients were included in the analysis. The incidence of CMV viremia was 4.9% and 50.0% (P < 0.001) in the prophylactic versus preemptive cohort, respectively, at 3 months post-transplant. The incidence of CMV viremia was 24.6% and 8.3% (P = 0.026) in the prophylactic versus preemptive cohort, respectively, at 6 months post-transplant. There were no statistical significant differences in the secondary outcomes between both cohorts. In conclusion, there is a statistical significant difference in time to onset of CMV viremia; however, the use of either prophylactic or preemptive strategy was not associated with significant negative clinical outcomes of CMV.

Topics: Adult; Aged; Antiviral Agents; Cohort Studies; Cytomegalovirus Infections; Female; Ganciclovir; Humans; Liver Transplantation; Male; Middle Aged; Neutropenia; Opportunistic Infections; Retrospective Studies; Treatment Outcome; Valganciclovir; Viremia

The Transplantation Society published guidelines on cytomegalovirus (CMV) management after solid organ transplantation in 2010, which provide recommendations on prevention, treatment, diagnostics, and resistance. We aimed to survey international clinicians on their posttransplantation CMV management practices with reference to these guidelines to see if they altered the management of clinicians caring for transplant patients.. The members of The Transplantation Society were emailed an electronic survey 12 months after the guideline publication.. A total of 155 clinicians responded, representing 126 centers in 41 countries. Overall, there was a high uptake of usage of the guidelines. High rates of initial CMV prevention were used (93%), with 46% using only universal prophylaxis, 21% only preemptive therapy, and 33% a hybrid combination dependent on recipient risk for CMV. Socioeconomic and geographic influence was evident, with 26% of respondents from developing countries using no CMV prevention, and more preemptive therapy used in Asia. Valganciclovir was the most common antiviral used, with dosing often below recommendations (33% in infection). Molecular monitoring was used by 84% of clinicians. Management of antiviral-associated neutropenia commonly included antiviral dose reduction or withdrawal (51%).. We conclude that there is significant geographic variation in CMV management after solid organ transplantation. Although the majority of clinicians adhere to consensus guidelines, opportunity exists to encourage better guideline uptake.

Topics: Antiviral Agents; Cytomegalovirus Infections; Developing Countries; Europe; Ganciclovir; Geography; Guideline Adherence; Health Knowledge, Attitudes, Practice; Humans; Internationality; Neutropenia; North America; Organ Transplantation; Practice Guidelines as Topic; Social Class; Societies, Medical; Surveys and Questionnaires; Valganciclovir

Congenital cytomegalovirus (CMV) is an important cause of sensorineural hearing loss. Ganciclovir treatment in the neonatal period may prevent hearing deterioration in infants with central nervous system (CNS) involvement. However, there are hardly any data regarding antiviral treatment begun beyond the neonatal period.. To describe the hearing outcome of infants with congenital CMV infection and CNS involvement treated beyond the neonatal period. To assess the tolerability and toxicity of prolonged valganciclovir treatment in these patients.. Retrospective case series of infants with congenital CMV infection and CNS involvement who started antiviral treatment beyond the neonatal period in Spain between 2008 and 2010. Hearing was tested by brainstem-evoked response at the time of diagnosis, 6 and 12 months after the beginning of treatment.. Thirteen cases were included. All received oral valganciclovir, and 4 also intravenous ganciclovir. Median valganciclovir treatment duration was 6 months and it was well tolerated. Six patients developed neutropenia, none requiring granulocyte colony-stimulating factor. Eleven children (85%) had hearing defects at baseline, compared to 50% at 12 months. By ears, 18 ears showed hearing loss at baseline (7 mild, 3 moderate, 8 severe). At 12 months, 9 remained stable, 7 had improved and none had worsened. In 8 normal ears at baseline, no deterioration was found at 12 months.. Valganciclovir treatment is well tolerated. It may improve or preserve the auditory function of congenitally cytomegalovirus-infected patients treated beyond the neonatal period for at least one year after the beginning of antiviral treatment.

Topics: Antiviral Agents; Cytomegalovirus Infections; Drug Administration Schedule; Ganciclovir; Hearing Loss, Sensorineural; Humans; Infant; Neutropenia; Retrospective Studies; Treatment Outcome; Valganciclovir

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.

Topics: Adult; Antigens, Viral; Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; Drug Substitution; Drug Therapy, Combination; Everolimus; Ganciclovir; Heart Transplantation; Heart-Assist Devices; Humans; Immunosuppressive Agents; Male; Mycophenolic Acid; Neutropenia; Opportunistic Infections; Sirolimus; Valganciclovir

Congenital cytomegalovirus infection is the most common cause of nonhereditary sensorineural hearing loss and an important cause of psychomotor retardation. Earlier studies showed that 6-weeks' treatment with ganciclovir, starting in the neonatal period, prevented hearing deterioration at 6 months, but in one-fifth of the infants, the effect was not sustained at age 12 months. The aim of this preliminary retrospective study was to investigate the effectiveness and safety of long-term treatment with ganciclovir/valganciclovir for congenital cytomegalovirus infection. Twenty-three infants with culture-proven symptomatic congenital cytomegalovirus infection were treated with ganciclovir for 6 weeks followed by oral valganciclovir to age 12 months. Audiometry was performed at least three times in the first year, in addition to physical examination including neurological and developmental assessment. At age >or=1 year, hearing was normal in 76% of affected ears compared to baseline (54%). In 25 normal ears at birth no deterioration was found at >or=1 year. These results were significantly better than reported in a historical control group of similar infants treated for 6 weeks only (P= 0.001). Viral load monitoring demonstrated sustained virological response. Four of the children (18%) had mental retardation. The main side effect of treatment was transient neutropenia. In conclusion, prolonged therapy of symptomatic congenital CMV infection with intravenous ganciclovir followed by oral valganciclovir is safe, and it appears to lead to a better auditory outcome than short-term treatment.

Topics: Administration, Oral; Antiviral Agents; Audiometry; Child, Preschool; Cytomegalovirus Infections; Follow-Up Studies; Ganciclovir; Hearing; Hearing Loss, Sensorineural; Humans; Infant; Infant, Newborn; Injections, Intravenous; Neutropenia; Retrospective Studies; Treatment Outcome; Valganciclovir

Posttransplant leukopenia is frequently observed in renal transplant. Granulocyte colony-stimulating factor controls the production of functional neutrophils and their release into peripheral blood. Granulocyte colony-stimulating factor has been widely and frequently used for many conditions and disorders in the field of hematology and oncology.. We present the cases of valacyclovir-related and valganciclovir-related neutropenia in 2 renal transplant recipients.. Both cases had renal transplants from live donors. The first one was an 18-year-old man. Laboratory investigations revealed his leukocyte count as 1.7 x 10(9)/L. The patient was using mycophenolate mofetil, cyclosporine, and valganciclovir. Mycophenolate mofetil was stopped because he had neutropenia, and later, valganciclovir was also stopped because the neutropenia persisted. Because the neutropenia did not recover after we discontinued valganciclovir, the patient was administered granulocyte colony-stimulating factor. The neutrophil count increased to 2.2 x 10(9)/L (leucocyte count to 6.5 x 10(9)/L) after 24 hours. The second case was a 37-year-old man and was using mycophenolic acid, tacrolimus, and valacyclovir. Laboratory investigations revealed his leukocyte count to be 1.3 x 10(9)/L. Mycophenolic acid and valganciclovir were stopped owing to neutropenia. The patient was administered granulocyte colony-stimulating factor, and the neutrophil count increased to 3.8 x 10(9)/L (leucocyte count to 5.8 x 10(9)/L). The kidney functions did not deteriorate in either patient, and the patients' kidney functions were similar to baseline levels 12 months after surgery.. We conclude that granulocyte colony-stimulating factor can be used safely and effectively in renal transplant patients.

Topics: Acyclovir; Adolescent; Adult; Antiviral Agents; Cytomegalovirus Infections; Filgrastim; Ganciclovir; Granulocyte Colony-Stimulating Factor; Humans; Kidney Transplantation; Male; Neutropenia; Recombinant Proteins; Treatment Outcome; Valacyclovir; Valganciclovir; Valine

An increased incidence and magnitude of leukopenia during concomitant treatment with valganciclovir (VGC) and mycophenolate mofetil (MMF) has been reported.. To evalute the incidence and severity of leukopenia and neutropenia among liver recipients treated with VGC and related factors.. Retrospective analysis of clinical and analytical data related to leukopenia (<3000 leukocytes/mm(3)) and neutropenia (<900 neutrophils/mm(3)) in liver transplant patients who were treated with VGC from 2003 to 2007. We examined the influence of concomitant administration of MMF and development of subsequent infections.. Among 209 liver transplants, 40 treatments with VGC were prescribed in 37 patients (17.7%), 12 of which (30%) were associated with MMF. The patients has an average age of 49.7 +/- 12.7, body mass index (BMI) of 27.28 +/- 5.17, and Model for End-stage Liver Disease Score (MELD) 12.45 +/- 7.5. The daily average dose of VGC was 1440 +/- 446.5 mg and MMF, 1454.5 +/- 350.3 mg. We observed a decrease of 30% in initial leukocyte count (5353.7 +/- 2706.6) and 40% in neutrophil count (3600 +/- 2182.1). With no relationship to total dose or BMI-adjusted dose of VGC nor concomitant administration of MMF. The initial leukocyte count was significantly lower (4411 +/- 1930 vs 6206 +/- 3053; P = .03) and underwent a main drop (2344.7 +/- 1974.3 vs 898.1 +/- 2435.6; P = .04) when leukopenia developed. In the induced neutropenia group, previous leukocyte count (3797.1 +/- 1223.9 vs 5683.9 +/- 2829.3; P = .01), MELD (18.7 +/- 8.8 vs 11.1 +/- 6.6; P = .01), and the creatinine pretreatment (1.44 +/- 0.4 vs 1.09 +/- 0.3; P = .01) were significantly different. Subsequent infections induced by the leukopenia were not observed.. In our series, the concomitant use of VGC and MMF was not associated with a greater incidence of leukopenia and/or neutropenia than VGC administration alone. Previous leukocyte count was associated with them. MELD and renal dysfunction are factors related to severe neutropenia. Leukopenia was not associated with a greater incidence of infections.

Topics: Adult; Antiviral Agents; Body Mass Index; Creatinine; Cytomegalovirus Infections; Female; Ganciclovir; Graft Rejection; Humans; Immunosuppressive Agents; Incidence; Leukocyte Count; Leukopenia; Liver Failure; Liver Transplantation; Male; Middle Aged; Mycophenolic Acid; Neutropenia; Retrospective Studies; Risk Factors; Valganciclovir

Cytomegalovirus (CMV) is the most common viral infection after transplantation. Valganciclovir (VGC) is established for prophylaxis and treatment of CMV infections, but leukopenia which appears in 10% to 13% (severe in 4.9%) is the principal side effect. We have recently noted an increased incidence of leukopenia and severe neutropenia among our renal transplant patients and thought to identify the associated factors. We conducted a retrospective analysis of all kidney transplantations performed between January 2005 and December 2006. All patients received mycophenolate mofetil (MMF), tacrolimus, and steroids. VGC was used for targeted prophylaxis and preemptive therapy of CMV infection, with doses adjusted to renal function. Of the 64 patients undergoing renal transplantation 13 (20.3%) developed leukopenia within 3 +/- 2 months after transplantation with severe neutropenia in 5 (7.8%). All patients were on MMF and VGC (VGC 605 +/- 296 mg/d). Leukopenia was significantly associated with simultaneous liver-kidney transplantation and with second kidney transplantations (P < .01). The incidence of leukopenia was higher among patients under VGC since day 1 of transplantation (P = .008) with maximal incidence observed among patients prescribed 900 mg/d as opposed to those on lower doses (P < .01). There was no increase in CMV infection among patients with a low dose of VGC. No patient developed clinical CMV disease. In conclusion, VGC prophylaxis was associated with an increased frequency of leukopenia on MMF-tacrolimus treated patients or regimens. Low-dose VGC for CMV prophylaxis appeared to be as effective as high-dose treatment, and associated less frequently with leukopenia and neutropenia.

Topics: Antiviral Agents; Cytomegalovirus Infections; Ganciclovir; Humans; Immunosuppressive Agents; Kidney Transplantation; Leukopenia; Mycophenolic Acid; Neutropenia; Postoperative Complications; Valganciclovir

Topics: Administration, Oral; Antiviral Agents; Cytomegalovirus Infections; Female; Ganciclovir; Humans; Infant, Newborn; Neutropenia; Valganciclovir; Viral Load

Valganciclovir is a prodrug of ganciclovir which has been developed for the treatment of cytomegalovirus (CMV) retinitis in patients with AIDS. Oral valganciclovir is rapidly absorbed and hydrolysed to ganciclovir. The oral bioavailability of ganciclovir after oral valganciclovir administration is high. Oral valganciclovir 900 mg provides a daily exposure of ganciclovir comparable to that of intravenous ganciclovir 5 mg/kg. A single, randomised, nonblind study indicated that oral valganciclovir (900mg twice daily for 3 weeks then 900 mg once daily) and intravenous ganciclovir (5 mg/kg twice daily for 3 weeks then 5 mg/kg once daily) were equally effective in the treatment of newly diagnosed CMV retinitis in 160 patients with AIDS. Valganciclovir appears to have a similar tolerability profile to intravenous ganciclovir during induction therapy in patients with AIDS and newly diagnosed CMV retinitis. During maintenance therapy with valganciclovir, the most commonly reported adverse events included neutropenia, anaemia, thrombocytopenia, gastrointestinal (including diarrhoea, nausea, vomiting and abdominal pain), fever, headache, insomnia, peripheral neuropathy, paraesthesia and retinal detachment.

Topics: Acquired Immunodeficiency Syndrome; Administration, Oral; Anemia; Antiviral Agents; Biological Availability; Cytomegalovirus Retinitis; Fever; Ganciclovir; Gastrointestinal Diseases; Headache; Humans; Infusions, Intravenous; Neutropenia; Paresthesia; Peripheral Nervous System Diseases; Prodrugs; Randomized Controlled Trials as Topic; Retinal Detachment; Sleep Initiation and Maintenance Disorders; Thrombocytopenia; Valganciclovir