Community-acquired respiratory syncytial virus and parainfluenza virus infections after hematopoietic stem cell transplantation: The Fred Hutchinson Cancer Research Center experience

AbstractCommunity respiratory viruses (CRVs) are an important cause of morbidity and mortality among recipients of hematopoietic stem cell transplants (HSCT). At the Fred Hutchinson Cancer Research Center, respiratory syncytial virus (RSV) and parainfluenza virus (PIV) infections in HSCT recipients have been studied intensively for more than a decade. Over time, mortality from these infections has declined as the approach to diagnosis has become more aggressive and more stringent preventive measures have been instituted. However, mortality among HSCT recipients with RSV or PIV pneumonia remains high. Uncontrolled studies at our center suggest that prompt therapy with aerosolized ribavirin has reduced mortality from RSV pneumonia but does not appear to affect the course of established PIV pneumonia. Two controlled clinical trials of ribavirin therapy for RSV infection in HSCT recipients are in progress.Biol Blood Marrow Transplant 2001;7 Suppl:11S-15S

Rhinovirus Infections in Hematopoietic Stem Cell Transplant Recipients with Pneumonia

Little is known about the impact of human rhinovirus (HRV) and coronavirus infections in hematopoietic stem cell transplant (HSCT) recipients. We tested bronchoalveolar lavage (BAL) samples obtained from HSCT recipients with acute pulmonary infiltrates for HRV (n = 122) and coronavirus (n = 46) by reverse-transcriptase polymerase chain reaction. HRV RNA was detected in 6 (8%) of 77 patients, and coronavirus RNA was detected in 0 of 46 of BAL samples from HSCT recipients. The fatality rate in HRV-infected patients was high (83%), but all patients had significant coinfections, and the overall mortality rate was not different from that of patients who were negative for HRV in BAL samples. These results suggest that HRV may be a cause of lower respiratory tract infections in HSCT recipients and that its detection in BAL samples is associated with frequent copathogens. Whether the poor prognosis is due to HRV or the copathogen is not clea

Development of multiplexed real-time quantitative polymerase chain reaction assay for detecting human adenoviruses.

Adenoviruses (AdVs) have been associated with a wide variety of human disease and are increasingly recognized as viral pathogens that can cause significant morbidity and mortality in immunocompromised patients. Early detection of AdV DNA in plasma and sterile fluids has been shown to be useful for identifying patients at risk for invasive AdV disease. Because of the large number of existing Adv types, few real-time quantitative AdV polymerase chain reaction (PCR) assays published effectively cover all AdV types. We designed a series of AdV PCR primers and probes and empirically multiplexed them into 2 separate real-time PCR assays to quantitatively detect all 49 serotypes of human AdV (types 1-49) available from American Type Culture Collection. We then subsequently multiplexed all the primers and probes into 1 reaction. The sensitivity of these assays was determined to be less than 10 copies per reaction (500 copies/mL plasma). In a retrospective evaluation, we detected all 84 clinical AdV isolates isolated in cell culture from patients undergoing hematopoietic stem cell transplantation between 1981 and 1987. Prospective analysis of 46 consecutive clinical samples submitted for AdV testing showed greater sensitivity and equal specificity of the AdV PCR than viral culture. This real-time PCR assay allows rapid, sensitive, and specific quantification of all currently defined AdVs into either 2 or 1 multiplex assay for clinical samples

Fourth European Conference on Infections in Leukaemia (ECIL-4): Guidelines for Diagnosis and Treatment of Human Respiratory Syncytial Virus, Parainfluenza Virus, Metapneumovirus, Rhinovirus, and Coronavirus

Respiratory viruses have been recognized as a significant cause of morbidity and mortality in patients with leukemia and those undergoing hematopoietic stem cell transplantation. The risk for lower respiratory tract infections and a fatal outcome appears to depend on the intrinsic virulence of the specific community-acquired respiratory virus as well as factors specific to the patient, the underlying disease, and its treatmen

Effect of conditioning regimen intensity on CMV infection in allogeneic hematopoietic cell transplantation.

Nonmyeloablative conditioning is less toxic and results in initial establishment of mixed hematopoietic T cell chimerism for up to half a year with prolonged presence of host T cell immunity. In this study, we examined whether this translates into differences in the risks and/or severity of cytomegalovirus (CMV) infection and disease. We analyzed data from 537 nonmyeloablative (NM-HCT) and contemporaneous 2489 myeloablative hematopoietic cell transplant (M-HCT) recipients. In CMV seropositive recipients, no difference in the overall hazards of CMV infection at any level (adjusted hazard ratio [adj. HR] 0.9, 95% confidence interval [95% CI]: 0.7-1.0, P = .14) was noted; however, NM-HCT was associated with a lower risk of high-grade CMV infection (adj. HR 0.7, 95% CI: 0.5-0.9, P = .02). CMV disease rates were similar between the groups during the first 100 days after HCT, but NM-HCT recipients had an increased risk of late CMV disease (adj. HR 2.0, 95% CI 1.2-3.4). The increased risk of late CMV disease after NM-HCT was pronounced during the earlier years of the study period, but not detectable in more recent years. Contrary to earlier reports, survival following CMV disease was not reduced after NM-HCT when compared to M-HCT recipients. These results suggest that residual host cells after NM-HCT reduce progression to higher CMV viral load in NM-HCT recipients; however, this effect does not appear to protect against serious complications of CMV. Therefore, CMV prevention strategies in NM-HCT recipients should be similar to those used in M-HCT recipients

Outcome of Respiratory Syncytial Virus Lower Respiratory Tract Disease in Hematopoietic Cell Transplant Recipients Receiving Aerosolized Ribavirin: Significance of Stem Cell Source and Oxygen Requirement

AbstractRespiratory syncytial virus (RSV) infection is an important complication after hematopoietic cell transplantation (HCT), and RSV lower respiratory tract disease (LRD) results in substantial early mortality and late airflow obstruction among survivors. Factors associated with poor outcome are unknown. We evaluated the effect of transplant and treatment factors on overall survival, mortality from respiratory failure, and pulmonary function among 82 HCT recipients who had RSV LRD between 1990 and 2011. All patients received aerosolized ribavirin. In multivariable analyses, only the use of marrow or cord blood as graft source (adjusted hazard ratio [aHR], 4.1; 95% confidence interval [CI], 1.8 to 9.0; P < .001) and oxygen requirement (aHR, 3.3; 95% CI, 1.5 to 6.7; P = .003) remained independently associated with overall mortality and death due to respiratory failure (aHR, 4.7; 95% CI, 1.8 to 13; P = .002 and aHR, 5.4; 95% CI, 1.8 to 16; P = .002, respectively). Antibody-based treatments, including intravenous immunoglobulin and palivizumab, were not independently associated with improved outcome and did not alter the associations of the graft source and oxygen requirements in statistical models. In conclusion, use of peripheral blood stem cells as graft source and lack of oxygen requirement at diagnosis appear to be important factors associated with improved survival of HCT recipients with RSV LRD. These results may explain differences in outcomes reported from RSV infection over time and may guide the design of future interventional trials