Respiratory Syncytial Virus (RSV) Immune Globulin Intravenous Therapy for RSV Lower Respiratory Tract Infection in Infants and Young Children at High Risk for Severe RSV Infections

Summary:Respiratory syncytial virus (RSV) has been reported as a cause of death among autologous peripheral blood stem cell (ASCT) and marrow recipients and recommendations for therapy with aerosolized ribavirin plus intravenous immunoglobulin (IVIG) made. This therapy is expensive, may be toxic, and causes a significant disruption of patient care. The purpose of this study was to evaluate the morbidity and mortality of RSV infections in patients with multiple myeloma undergoing ASCT without ribavirin therapy. During the months of February-April 1997, 10 consecutive patients (median age 57 years, seven males) with advanced and heavily pretreated myeloma underwent ASCT while having active RSV upper respiratory tract infection. After melphalan (200 mg/m 2 ), all patients became neutropenic (Ͻ1000 cells/mm 3 ) for a median of 7 days. Ribavirin was not given to any patient. No patient developed lower respiratory tract infection, required transfer to intensive care or died at a median follow-up of 8 months. One patient developed tracheobronchitis requiring oxygenation by nasal cannula. No delay in the treatment of the underlying myeloma was incurred. RSV infection may not necessarily be a contraindication for ASCT or an indication for therapy with aerosolized ribavirin. Additional studies are needed to confirm our preliminary findings. Keywords: multiple myeloma; ribavirin; RSV infection; bone marrow or stem cell transplantation Viral infections represent a challenging problem in immunocompromised patients. 1-3 Respiratory syncytial virus (RSV) is an important community and nosocomial respiratory pathogen for infants, young children and immunocompromised adults. 4 RSV causes especially severe disease in the prematurely born, the elderly and in patients with chronic cardiopulmonary diseases or T cell deficiencies, such as peripheral stem cell or marrow transplant recipients. 5 solized ribavirin and high-dose IVIG has been recently recommended for the treatment of RSV upper respiratory tract infections on the basis of an uncontrolled study from a single center. 6 However, this approach has never been evaluated in randomized trials in adults. The trials in pediatric RSV infections gave conflicting results: some showing clinical improvement, 7-13 while others showed no benefit [14][15][16][17][18] or even a detrimental effect (eg prolonged duration of hospitalization, intensive care unit stay, duration of hypoxia, and mechanical ventilation) [19][20][21][22][23][24] (Table 1). A recent metaanalysis of randomized trials concluded that the administration of ribavirin in pediatric RSV infections is not supported by the clinical studies and does not result in decreases in length of hospital stay or mortality rate. 18 More recent studies which included significantly larger numbers of patients than earlier reports, concluded that aerosolized ribavirin was detrimental to infants with RSV infection. [20][21][22]24

Section: Discussionmentioning

confidence: 73%

Patients with multiple myeloma may safely undergo autologous transplantation despite ongoing RSV infection and no ribavirin therapy

Aslan

Fassas

Siegel

et al. 1999

“…6,[27][28][29][30][31][32][33] The commercially available forms of these drugs are RespiGam (MedImmune, Gaithersburg, MD, USA), a pooled human polyclonal IgG intravenous hyperimmune globulin with high RSV microneutralization titers and Synagis (MedImmune), an intramuscularly administered humanized monoclonal Ab directed against the F glycoprotein of RSV. These drugs have been approved by the FDA for prophylaxis against serious complications of RSV infection in high risk infants and young children in January 1996 and June 1998.…”

Section: Discussionmentioning

confidence: 99%

“…Ribavirin was combined with IVIG because studies in vitro, in animal models, and in children had suggested that immunoglobulin may be of benefit for RSV infections prophylactically as well as therapeutically. [15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33] In addition, the University of Texas MD Anderson Cancer Center (MDACC) experience with combination aerosolized ribavirin and IVIG for the therapy of RSV pneumonia in adult BMT recipients and adults with leukemia had been favorable. 6,8 Bone Marrow Transplantation…”

mentioning

confidence: 99%

Respiratory syncytial virus upper respiratory tract illnesses in adult blood and marrow transplant recipients: combination therapy with aerosolized ribavirin and intravenous immunoglobulin

Ghosh

Champlin

Englund

et al. 2000

181

123

Summary:Respiratory syncytial virus (RSV) is an important cause of serious respiratory illness in blood and marrow transplant (BMT) recipients. In some subsets of these immunocompromised patients, RSV upper respiratory illnesses frequently progress to fatal viral pneumonia. The frequency of progression to pneumonia is higher during the pre-engraftment than during the postengraftment period. Once pneumonia develops, the overall mortality is 60-80%, regardless of the treatment strategy. We performed a pilot trial of therapy of RSV upper respiratory illnesses using aerosolized ribavirin and IVIG (500 mg/kg every other day), with the goal of preventing progression to pneumonia and death. Two dosages of ribavirin were used: a conventional regimen (6 g/day at 20 mg/ml for 18 h/day) and a high-dose short-duration regimen (6 g/day at 60 mg/ml for 2 h every 8 h). Fourteen patients were treated for a mean of 13 days (range: 7-23 days). In 10 (71%) patients, the upper respiratory illness resolved. The other four (29%) patients, three of whom were in the pre-engraftment period, developed pneumonia, which was fatal in two. The most common adverse effect was psychological distress at being isolated within a scavenging tent. In conclusion, prompt therapy of RSV upper respiratory illnesses in BMT recipients with a combination of aerosolized ribavirin and IVIG was a safe and promising approach to prevent progression to pneumonia and death. Bone Marrow Transplantation (2000) 25, 751-755. Keywords: respiratory; syncytial; virus; therapy; ribavirin; transplant Respiratory syncytial virus (RSV) is a frequent cause of acute respiratory illness in autologous as well as allogeneic blood and marrow transplant (BMT) recipients. 1-11 These infections usually occur during community outbreaks, which typically occur in a seasonal fall-winter pattern. In

“…Moreover, proving a treatment benefit in a complicated condition such as this by comparing one uncontrolled series to another is difficult. Indeed, despite higher RSV loads being linked to disease severity, 24 large well controlled trials studying RSV-IGIV in the treatment of established RSV disease in previously healthy 25 and high risk 26 infants have failed to show a statistically significant treatment effect (a favorable trend was observed in the previously healthy group 25 ). The reason is most likely due to the fact that infection in immuno-competent patients is rapidly cleared, giving little time for the rapid reduction of virus achieved with passive antibody treatment to manifest itself as observable clinical improvement.…”

Section: Tablementioning

confidence: 99%

Respiratory syncytial virus immune globulin treatment of lower respiratory tract infection in pediatric patients undergoing bone marrow transplantation – a compassionate use experience

DeVincenzo

Hirsch²,

Fuentes³

et al. 2000

112

Summary:Respiratory syncytial virus (RSV) pneumonia in BMT recipients carries a mortality rate of approximately 50-70% despite ribavirin (Virazole) treatment. In both immunocompetent and immunocompromised animal models, RSV neutralizing antibodies rapidly reduce pulmonary virus load after a single dose. RSV-IGIV (RespiGam) is an IgG immune globulin with high concentrations of RSV neutralizing antibody (Ͼ19 200 MU/ml). From June 1991 to February 1996, a compassionate-use protocol using RSV-IGIV for treatment of RSV infections was conducted. Eleven children at multiple centers, mean age 3.3 years (4 months to 9 years), were undergoing BMT and met the protocol criteria. They received a single 1500 mg/kg dose of RSV-IGIV infused over 12 h at a median of 5 days (1-37 days) after RSV symptom onset. Ten of these patients received prior or concurrent aerosolized ribavirin. Serum RSV neutralizing titers were measured in five patients and showed a 3-to 30-fold increase 24 h after RSV-IGIV infusion. Adverse events were mild. One of 11 (9.1%) patients died from their RSV illness (91% RSV survival). In comparison to previously published reports, RSV-IGIV treatment of RSV pneumonia in BMT patients may increase survival above that in such patients treated with ribavirin alone. Bone Marrow Transplantation (2000) 25, 161-165. Keywords: respiratory syncytial virus; bone marrow transplantation; immune globulin; treatment; ribavirin; palivizumab Respiratory syncytial virus (RSV) is a well recognized and often fatal complication of bone marrow transplantation. Upper or lower respiratory tract infection (URTI/LRTI) with RSV has been reported to occur in 7% to 20% of hospitalized BMT patients, primarily during the 6-month winter season (November to May). 1-3 Many of these RSV infected patients develop pneumonia and face a high risk of mortality. [1][2][3] The reported mortality rate in BMT patients who develop RSV-LRTI approaches 100% for those not treated with antivirals and 50% to 70% for those promptly treated with ribavirin (Virazole). [3][4][5][6][7][8][9][10][11][12][13] From the literature, it appears that there are no survivors among RSV-LRTI transplant patients who progress to mechanical ventilation before antiviral therapy has been initiated. 2,12 Although RSV pneumonia occurring more than 100 days post-BMT has been associated with lower mortality rates, 12,13 the mortality rate of RSV pneumonia does not differ before and after engraftment during the early post-transplant period. 3,14 Aerosolized ribavirin is the only Federal Drug Administration (FDA) approved drug for treatment of established RSV disease, 15 but its efficacy in BMT patients with RSV pneumonia is considered poor. The beneficial effects of immune globulin therapy on established RSV disease have been clearly demonstrated in experimental animals. In both immunocompetent and immunocompromised animal models of RSV infection, IgG immune globulin preparations have been shown to rapidly reduce the pulmonary virus load after a single large parenteral dose. [16][17][1...