M Boeckh

..Current evidence on the use of antiviral agents in the prevention of reactivation disease and management of exposure to VZV is discussed...

..Etiologies include myelotoxic agents, viral infections, and possibly transplant-related factors such as the intensity of the conditioning regimen and the source of stem cells...

..Due to the widespread use of quantitative CMV detection techniques to direct and monitor antiviral treatment, there is a great need for an assessment of the reproducibility of test results and better standardization of the assays...

..HHV-6 has been strongly associated with encephalitis and delayed platelet engraftment. Prospective studies are needed to further examine epidemiology, disease associations, and management strategies for these viruses...

..Prevention strategies may require targeting both the direct and indirect effects of CMV infection by immunologic or antiviral drug strategies...

..This article reviews the spectrum of pathogens, epidemiology, risk factors and clinical manifestations of infection, as well as recent advances in diagnostic and clinical management...

..Antiviral therapy initiated during the URI phase reduced the risk of LRD and hypoxemia...

..Prevention strategies should be targeted at patients in whom CMV reactivated during the first 3 months and those with poor CMV-specific immunity or low CD4 counts...

....

..Respiratory syncytial virus infection of the upper airways may progress to fatal pneumonia in hematopoietic cell transplant recipients. The safety and efficacy of aerosolized ribavirin in preventing disease progression is unknown...

..This article reviews current aspects of CMV diagnosis, prevention, and treatment in HCT recipients and defines areas of unmet medical need...

..Periods of prophylaxis longer than 12 months may be beneficial for those hematopoietic cell transplant recipients on continued immune suppression...

..Thus, high-dose acyclovir does not appear to improve survival when ganciclovir is given either at engraftment or for CMV pp65 antigenemia...

..Thus, primer optimization and improved DNA extraction techniques resulted in a plasma-based PCR assay that is significantly more sensitive than pp65 antigenemia and blood cultures for detection of CMV in blood specimens...

..The development of new drugs and immunologic strategies (adoptive transfer of CMV-specific T-cells and donor/recipient vaccination strategies) are important goals for the elimination of the negative impact of CMV in the HCT setting...

..Owing to continued clinical significance of CMV in the HSCT setting, new and more effective anti-CMV drugs with improved pharmacokinetic properties are urgently needed...

..Thus, palivizumab appears to be safe and well tolerated in HSCT recipients...

..Thus, there is no evidence that MSL-109 is beneficial in CMV-seropositive HSCT recipients...

..More trials are needed to evaluate whether the effects seen in observational studies are truly related...

..Therefore, CMV prevention strategies in NM-HCT recipients should be similar to those used in M-HCT recipients...

..Cytomegalovirus (CMV) disease occurs frequently after cessation of antiviral prophylaxis in CMV-seronegative kidney transplant recipients from seropositive donors (D+R-), and the risk factors are incompletely defined...

....

..We retrospectively assessed the occurrence of ganciclovir-resistant cytomegalovirus disease among transplant recipients who had received oral ganciclovir prophylaxis and highly potent immunosuppression...

..008). In conclusion, blood stem cell recipients have higher lymphocyte-subset counts and this appears to result in fewer infections. (Blood. 2001;97:3380-3389)..

..5x107] vs. <50 [range, <50-350] CMV DNA copies/mL plasma, respectively; P<.001). Quantitative PCR for CMV DNA in plasma appears to be useful for the identification of HSCT recipients at risk for CMV disease before engraftment...

..Therefore, nonmyeloablative HSCT patients should receive CMV surveillance beyond day 100 and pre-emptive ganciclovir treatment similar to that of myeloablative HSCT patients...

..BK virus seems to play a role in the development of HC and quantitative detection of BK DNA in plasma appears to be a marker of BK virus disease in HCT recipients...

....

..Two controlled clinical trials of ribavirin therapy for RSV infection in HSCT recipients are in progress...

....

....

..Human metapneumovirus (hMPV), a recently discovered respiratory virus, is associated with clinical disease in young and elderly persons...

..More effective strategies are needed to prevent invasive mold infections, which currently account for a notable proportion of nonrelapse mortality after nonmyeloablative allogeneic HCT...

..The aim of this study was to determine the probability of survival and prognostic factors associated with outcomes over a long period of time...

..004). Subclinical infection with PIV may help explain why infection-control programs that emphasize symptoms are effective against RSV and influenza but often not against PIV...

..2% [95% CI, 0%-0.8%]; P=.006), and in 0 patients in cohort 3 (cohort 2 vs. cohort 3, P=.3). Long-term use of suppressive prophylactic ACV appears to prevent the emergence of drug-resistant HSV disease in HCT...

..Currently available antiviral therapy appears to be inadequate in reducing viral shedding or mortality once pneumonia is established. (Blood. 2001;98:573-578)..

..Clinicians should appreciate the potential for the development of antiviral resistance to influenza antivirals in immunocompromised patients...

..Over the past decade, advances have been made in the care of patients undergoing transplantation. We conducted a study to determine whether these advances have improved the outcomes of transplantation...

..To effectively prevent VZV disease in long-term hematopoietic cell transplantation survivors, additional approaches such as vaccination will probably be required...

..Thus, community respiratory virus-associated airflow decline seems to be specific to viral species and infection localization...

..Subclinical CMV reactivation while on ganciclovir appears to be a potent stimulator of T-cell function. These findings have implications for vaccination and adoptive-immunotherapy strategies in this population...

....

..Ganciclovir, given for CMV prevention, may have a protective effect. Controlled treatment and prevention studies are warranted...

....

..The value of adenovirus plasma DNA detection as an indicator for adenovirus disease is unknown in the context of T cell-replete hematopoietic cell transplantation, of which adenovirus disease is an uncommon but serious complication...

..Although human herpesvirus 6 (HHV-6) is known to reactivate during hematopoietic stem cell transplantation (HSCT), the clinical significance of this finding is controversial...

..However, no data exist regarding the use of oseltamivir as prophylaxis among patients undergoing hematopoietic stem cell transplantation (HSCT)...

..However, in D(+)/R(-) subjects, mortality appears to be associated with bacterial and fungal infection, indicating a possible immunomodulatory effect of primary CMV infection that was undetected despite intensive monitoring...

..Because the risk for infections approaches that seen in allogeneic transplant recipients, infection surveillance, diagnostic work-up, and prevention strategies similar to those used in allogeneic recipients are warranted...

..To evaluate the relative sensitivity of respiratory virus detection in specimens from HCT recipients, we compared the results of conventional and quantitative molecular methods...

....

..All ganR isolates contained a UL97 mutation. GanR CMV infection occurs in nearly 10% of lung transplant recipients, despite preemptive antiviral therapy, and is more common among D+/R- patients...

..The results of in vitro studies and animal models suggest that combination therapy with azoles and echinocandins may have additive activity against Aspergillus species...

..94 [1.0-3.8], P = .05), but not for overall mortality or NRM. We propose that intensified strategies to prevent infections should be implemented in MDS patients with preexisting neutropenia who undergo HSCT...

..In an era of "universal leukoreduction," the abandonment of CMV-seronegative inventories appears premature, particularly among populations at high risk of CMV disease that do not receive active surveillance...

..We conclude that initial treatment with low-dose glucocorticoids for patients with grades I-II GVHD did not compromise disease control or mortality and was associated with decreased toxicity...

....

....

..Few data exist on respiratory virus quantitation in lower respiratory samples and detection in serum from hematopoietic cell transplant (HCT) recipients with respiratory virus-associated pneumonia...

..The incidence and clinical and virologic aspects of ganciclovir-resistant cytomegalovirus (CMV) disease have not been well-characterized in heart transplant recipients...

..Thus, reconstitution of T-cell immunity in immunodeficient patients by cell therapy or by vaccination may need to target multiple viral antigens to completely restore immunologic control of CMV...

....

....

..Other factors significantly associated with delayed immune recovery were advanced donor age, low numbers of CD34 and T cells in the graft, and development of graft-versus-host disease...

..We studied immune reconstitution in 51 recipients of HLA-identical hematopoietic cellular transplant (HCT) after nonmyeloablative conditioning compared to a reference group of 67 recipients after myeloablative conditioning...

....

..69). There was no difference in overall or fungal-free survival. Itraconazole appears to prevent IMI in the subset of patients who tolerate the drug; however, toxicities and poor tolerability limit its success as prophylactic therapy...

..The concept of nosocomial transmission should be expanded to include the OPD for immunosuppressed patients...

..Serological testing of donors can identify patients who are at highest risk for HSV-related morbidity, for whom prolonged prophylaxis or donor vaccination (once available) could be considered...

..These data suggest that azole antifungals, through differential inhibition of hepatic cytochrome P-450 isoenzymes, affect CY metabolism and conditioning-related toxicities...

..In contrast, neither recipient immunization on days -1 and 50 nor donor immunization on day -20 appears to be efficacious for polysaccharide antigens and poorly immunogenic protein neo-antigens...

..We also summarize infection control and vaccination strategies for patients, family members, and caregivers...

....

..We examined the role of TLR polymorphisms in conferring a risk of invasive aspergillosis among recipients of allogeneic hematopoietic-cell transplants...

..We describe an outbreak of varicella with likely breakthrough disease in a population of pediatric cancer patients in October 2004...

..7x10(3) vs. 0 copies/mL; P=.0006). BK viremia also was strongly associated with postengraftment hemorrhagic cystitis in a time-dependent analysis (P=.004)...

..Risk factors for acquisition, progression to pneumonia, and the effect of antiviral therapy are unknown...

..Treatment was well tolerated and associated with improvement in oxygenation and symptoms, along with rapid clearance of PIV. DAS181 should be systematically evaluated for treatment of PIV infection in transplant recipients...

..5, P=0.007). Our data suggest that extension of PCP prophylaxis may be beneficial in high-risk autograft recipients. Further study of long-term anti-infective prophylaxis based on patient risk factors after SCT appear warranted...

..aeruginosa infections are associated with high recurrence rates and mortality in this immunocompromised population. Aggressive attempts to reduce immunosuppression and to treat copathogens may help during the initial infection...

..ADV infection was a major cause of death in 17 patients. CONCLUSIONS: ADV nephritis is a specific renal complication in HSCT patients that can be diagnosed by renal biopsy in patients with hematuria and adenoviruria...

..Alternatively, high stringency hybridization conditions may be utilized, detecting BKV only. BK associated tubular necrosis is clearly demonstrated in two cases of BK nephritis...

..83; 95% CI, 1.38-16.75, P = .013). These data suggest that transcriptional regulation of the LBP gene contributes to the risk for developing GN bacteremia and death after HCT...

..These studies will improve our understanding of the interaction between respiratory viruses and late pulmonary complications after HCT, which will ultimately enable us to formulate more rational treatment strategies. ..