Successful therapy with ribavarin of late onset respiratory syncytial virus pneumonitis complicating allogeneic bone transplantation

Summary A 21-year-old patient developed interstitial pneumonitis nine months post bone marrow transplant for acute myeloblastic leukaemia. Immunofluorescence of broncheoalveolar lavage fluid revealed the presence of respiratory syncytial virus (RSV). Aerosolized ribavarin therapy resulted in rapid resolution of the pneumonitis with full recovery without any side effects. Ribavarin therapy should be considered early in the management of BMT patients who develop RSV pneumonitis.     

Ribavirin therapy of adult respiratory syncytial virus pneumonitis

Respiratory syncytial virus is a common respiratory tract pathogen in infants. Pulmonary infection in adult and elderly populations can occur with severe and even fatal pneumonitis having been reported in several recent outbreaks. We present a previously healthy adult patient who developed respiratory syncytial virus pneumonia severe enough to require mechanical ventilation. Antiviral therapy with aerosolized ribavirin was successfully undertaken and the patient recovered completely. Respiratory syncytial virus infection should be considered in the differential diagnosis of atypical adult pneumonias. Aerosolized ribavirin therapy may be beneficial in treatment.     

Economic and long-term benefits of ribavirin therapy on respiratory syncytial virus infection

Ribavirin is a broad-spectrum antiviral agent. Administered as an aerosol, it has been shown to be clinically effective in improving the signs and symptoms of viral bronchiolitis in infancy, particularly cases due to respiratory syncytial virus (RSV). This paper reviews the evidence for economic and/or long-term clinical benefits from using ribavirin in the acute illness. There are data to suggest that use of ribavirin may lead to a reduction in therapeutic interventions and duration of hospital stay, with associated savings in hospital costs. Ribavirin reduces the production of RSV-specific IgE, and (in vitro) inhibits the release of inflammatory mediators from mast cells, suggesting that there could be beneficial effects on the incidence of postbronchiolitis wheezing. Confirmatory studies are in progress.     

Palivizumab treatment of respiratory syncytial virus infection after allogeneic hematopoietic stem cell transplantation.

Among 40 allogeneic stem cell transplant recipients who developed symptomatic respiratory syncytial virus infection, including 22 patients with lower respiratory tract infection, 19 received palivizumab (9 of whom had upper respiratory tract disease). Palivizumab did not prevent progression to lower respiratory infection and had no impact on the overall survival rate.     

A risk‐adapted approach to treating respiratory syncytial virus and human parainfluenza virus in allogeneic stem cell transplantation recipients with oral ribavirin therapy: A pilot study

Here we report the applicability of a protocol based on clinical conditions and risk factors (RFs) for managing 35 allogeneic hematopoietic stem cell transplantation (allo‐HSCT) recipients who developed a total of 52 episodes of respiratory viral infections (RVIs) caused by respiratory syncytial virus (RSV; n=19), human parainfluenza virus (HPIV; n=29), or both (n=4) over a 2‐year study period. Risk categories were classified as high risk (cat‐1) when the immunodeficiency scoring index was ≥3 and/or ≥3 RFs and/or ≥1 co‐infective virus(es) were present; the remaining cases were classified as low risk (cat‐0). The presence of two or more signs or symptoms including fever (T>38 °C), sinusitis, otitis, sore throat, tonsillitis, or baseline C‐reactive protein increased by >2‐fold at the time of the RVI, was considered a clinically‐intense episode (CIE). Overall, 34 out of 52 episodes (65%) were limited to upper respiratory tract infections (URTIs). Overall, 26 (50%) received oral ribavirin. Twenty‐four of 40 (60%) cat‐1 episodes were treated, compared to 2 of 12 (17%) cat‐0 RVIs (P=.01), while 17 of the 25 (68%) CIEs were treated compared to 9 of the remaining 27 (33%) episodes (P=.02). Regardless of antiviral therapy, the overall resolution rate was 100% for URTI and 95% for lower respiratory tract infection; the virus‐related mortality was low (4%). In conclusion, the use of a risk‐adapted protocol to guide therapeutic decisions for allo‐HSCT recipients with RSV or HPIV RVIs is feasible and may limit unnecessary antiviral therapy.     

The outcome of 26 patients with respiratory syncytial virus infection following allogeneic stem cell transplantation

Respiratory syncytial virus (RSV) is known to cause acute lung injury in the immunocompromised host, especially recipients of bone marrow allografts. Specific prognostic factors for the development of severe life-threatening disease remain to be identified as does the optimum treatment of established disease. Over a 5-year period the incidence and outcome of RSV in BMT recipients was analysed retrospectively. Prognostic factors assessed included type of transplant, engraftment status at the time of infection, the presence of lower respiratory tract disease, viral genotype and treatment received. During the study period, 26 of 336 (6.3%) allogeneic stem-cell recipients were identified as having RSV. Five patients (19.2%) died as a direct result of RSV. One patient died secondary to an intracranial bleed with concomitant RSV. There were four patients with graft failure (two primary and two secondary) attributable to the presence of RSV, two of whom subsequently died of infections related to prolonged myelosuppression. The presence of lower respiratory tract infection and a poor overall outcome was the only statistically significant association. Unrelated donor transplants and AML as the underlying disease appeared to be associated with a poorer outcome. Engraftment status, viral genotype and RSV treatment received did not correlate with outcome. We conclude that future studies are required to identify early sensitive and reproducible prognostic factors of RSV in the immunocompromised host. The roles of intravenous and nebulised ribavirin need to be clarified by prospective controlled trials.     

Fatal respiratory syncytial virus pneumonitis in a previously healthy child

Respiratory syncytial virus (RSV) is a cause of significant morbidity and mortality in infants and children with an immunocompromised status or a congenital heart disease. The following case describes a 6 8/12-year-old, previously normal child who had a fatal interstitial pneumonitis caused by RSV. Documentation of RSV as the etiologic agent and documentation of her immune status are presented. In light of recent advances in the rapid diagnosis and treatment of RSV, this virus should be considered in children with an unusual interstitial pneumonitis regardless of their known immunologic status.     

Association of cytomegalovirus interstitial pneumonitis with HLA-type following allogeneic bone marrow transplantation

Certain human leukocyte antigens may increase the risk of cytomegalovirus interstitial pneumonitis, an important complication of bone marrow transplantation. The prevalence of this pneumonitis was compared between patients possessing either HLA-B51 or HLA-B52 and patients without either antigen. The role of tumor necrosis factor-alpha in cytomegalovirus interstitial pneumonitis was also studied. Among 72 patients undergoing allogeneic bone marrow transplantation at our institution during the past 5 years, HLA-B51 or -B52 was detected in 29. Among these 29 patients, 13 (45%) developed cytomegalovirus interstitial pneumonitis, a significantly higher rate (P < 0.001) than among patients without these HLA types (4/43, 9%). In the pre-conditioning and stable phases, tumor necrosis factor-alpha levels were higher in patients with HLA-B51 or HLA-B52 than in patients without (P < 0.05; t-test). Throughout the period from pre-conditioning to around day 40, except on day 0, tumor necrosis factor-alpha levels were also significantly higher (P < 0.05 to P < 0.001) in patients developing cytomegalovirus infection than in those without it. These results suggest that HLA-B51 and HLA-B52 may be risk factors for cytomegalovirus interstitial pneumonitis after bone marrow transplantation, with an increase of tumor necrosis factor-alpha also being involved.     

Inhaled ribavirin therapy in adult respiratory syncytial virus-induced acute respiratory distress syndrome

Respiratory syncytial virus (RSV) infection-induced acute respiratory distress syndrome (ARDS) in previously healthy adults is rare, but the overall mortality rate is 40-60%. Inhaled ribavirin is approved for the treatment of hospitalized infants and young children with severe lower respiratory tract infections due to RSV. We present the case of an adult female with RSV pneumonia-induced ARDS who was successfully treated with inhaled ribavirin and whose pulmonary function was restored to near normal. The role of inhaled ribavirin in adults is controversial, but it might have a therapeutic potential for severe RSV infection-induced ARDS in adults.     

Successful liver allografts in mice by combination with allogeneic bone marrow transplantation.

Successful liver allografts were established by combination with allogeneic bone marrow transplantation. When liver tissue of BALB/c (H-2d) or C57BL/6J (H-2b) mice was minced and grafted under the kidney capsules of C3H/HeN (H-2k) mice, it was rejected. However, when C3H/HeN mice were irradiated and reconstituted with T-cell-depleted BALB/c or BALB/c nu/nu bone marrow cells, or with fetal liver cells of BALB/c mice, they accepted both donor (stem-cell)-type (BALB/c) and host (thymus)-type (C3H/HeN) liver tissue. Assays for both mixed-lymphocyte reaction and induction of cytotoxic T lymphocytes revealed that the newly developed T cells were tolerant of both donor (stem-cell)-type and host (thymus)-type major histocompatibility complex determinants. We propose that liver allografts combined with bone marrow transplantation should be considered as a viable therapy for patients with liver disease such as liver cirrhosis and hepatoma.     

Dual infection with Pneumocystis carinii and respiratory viruses complicating bone marrow transplantation.

Pneumonia due to dual infection with Pneumocystis carinii and respiratory viruses is a rare but formidable complication of bone marrow transplantation. We report here two cases of viral infections complicating P. carinii pneumonia in bone marrow transplant recipients who, at the time of infection, were not taking P. carinii prophylaxis. Both patients died following the pneumonia. Potential factors contributing to the dual infection included graft-versus-host disease, high-dose steroids and cyclosporin A. P. carinii prophylaxis should be continued for 12 months, or longer in bone marrow transplant recipients requiring prolonged immunosuppressive therapy. As specific antiviral therapy becomes available for some respiratory viral infections, performing regular viral surveillance cultures and responding with active early treatment may help improve the outcome in these immunocompromised patients.     

Interstitial pneumonitis after allogeneic bone marrow transplantation. Nine-year experience at a single institution

Of 386 patients with allogeneic bone marrow transplants (BMT) treated during a 9-year interval, 166 developed interstitial pneumonitis (IP). Idiopathic and cytomegalovirus (CMV) IP constituted 90% of the 113 cases in which tissue was examined. Risk factors for IP overall were acute graft-versus-host disease (AGVHD), remote transplant date, the diagnosis of leukemia, and GVHD prophylaxis with agents other than cyclosporine. Risk factors for CMV IP were pre-transplant CMV seropositivity, CMV excretion, age greater than 10 years, AGVHD, GVHD prophylaxis with agents other than cyclosporine, and a remote transplant date. Patients transplanted for aplastic anemia were at lower risk for idiopathic IP than those transplanted for leukemia. The incidence of IP in patients given busulfan plus cyclophosphamide was equivalent to that in patients receiving cyclophosphamide plus total body irradiation. The incidence of idiopathic IP remained constant over this 9-year period while CMV IP declined significantly.