The natural history of respiratory syncytial virus infection in cancer and transplant patients: implications for management

Abstract

Respiratory syncytial virus (RSV) has been reported to cause severe morbidity and mortality among cancer patients receiving chemotherapy with or without autologous peripheral blood stem cell transplantation (APBSCT). However, little is known about the natural history of this infection in these patients, and current standard practice, aerosolized ribavirin plus intravenous immunoglobulin (IVIG), is extremely expensive, difficult to use, and not supported by controlled clinical trials. The purpose of this observational study was to determine the frequency, seasonality, morbidity, and mortality of RSV infection in a group of cancer pa- IntroductionRespiratory syncytial virus (RSV) is thought to cause rare but severe community and nosocomial respiratory infections in immunocompromised adults, including cancer patients, [1][2][3][4][5][6][7][8][9] and to occur almost exclusively during winter. [10][11][12][13] Recommendations for the management of RSV infections in cancer patients include strict infection control measures, delay in the therapy for the underlying disease, and treatment with aerosolized ribavirin plus high-dose intravenous immunoglobulin (IVIG). [3][4][5][6][7][8][9]14 These strategies are associated with huge costs, toxicity, disruption of patient care activities, and delay in treating the underlying cancer. 15,16 Furthermore, these recommendations were based on studies that did not evaluate a homogenous patient population and, most important, failed to include a control group whose respiratory cultures were negative for RSV. We have previously reported on 10 myeloma patients with positive respiratory tract cultures for RSV who successfully underwent autologous peripheral blood stem cell transplantation (APBSCT) without receiving RSV-specific therapy. 17 In this prospective observational study, we sought to determine the incidence and seasonality of RSV infection in a homogenous group of cancer patients not receiving RSV-specific therapy. We also determined the type of and risk for complications associated with RSV by including a control group whose respiratory cultures were negative for this virus. Patients, materials, and methodsCancer patients receiving cytotoxic chemotherapy, with or without APBSCT or allogeneic bone marrow transplantation (allo-BMT), were evaluated at the University of Arkansas for Medical Sciences in Little Rock. A written informed consent for specimen collection was obtained in keeping with institutional policies. This evaluation occurred over a period of 12 months (October 3, 1997, to October 14, 1998. Nasopharyngeal washings were collected into a sterile cup and transported on wet ice to the virology laboratory, generally within 2 hours. Bronchoalveolar lavage specimens and tissue obtained by open lung biopsy and autopsy were also collected for culture when available, with tissue specimens homogenized prior to culture inoculation. Specimens were inoculated into tubes containing human diploid embryonic lung (MRC-5) fibroblast cells and checked daily during the first week and ...

Risk factors and containment of respiratory syncytial virus outbreak in a hematology and transplant unit

“…Although RSV has been associated with fatal pneumonia without evidence of superinfections by other pathogens, 10 other groups have provided evidence that RSV positivity in immunocompromised patients was not associated with any adverse outcome. 7,8 It is indeed difficult to assess to what extent the fatal outcome could be attributed to the RSV infection in our cohort, because this particular population typically suffers from several comorbidities and co-infections. The fatal cases in the outbreak described here showed that the majority (11/14 patients) had co-infections with other viral (BK virus, CMV, EBV, Herpes simplex virus-in one case acyclovir resistant), bacterial (for example, multi-drug resistant Pseudomonas aeruginosa) or fungal (Aspergillus fumigatus) pathogens.…”

“…3 Although RSV is usually a self-limiting disease causing only mild symptoms of upper respiratory tract infection disease (URTID) or no symptoms at all, 4 it may be associated with severe LRTID in elderly or immunocompromised adults. 5,6 Morbidity and mortality rates reported in the literature are heterogeneous, the relevance of RSV infections in terms of outcome for patients undergoing autologous or allogeneic SCT ranging from none 7,8 to a mortality rate of up to 78%. [9][10][11][12][13][14] The impact of RSV on fatal outcome in this often multimorbid patient population might be difficult, if not impossible, to assess.…”

Intravenous ribavirin for respiratory syncytial viral infections in pediatric hematopoietic SCT recipients

“…or oral applications, but no controlled clinical trials to reach treatment consensus have been conducted. 6,13 Aerosolized ribavirin has been the most frequently used treatment for RSV after HSCT. 10 Its use has been limited on account of the lack of proven efficacy and potential toxicity to caregivers exposed to the drug, including potential teratogenicity.…”

“…No RSV-specific gamma globulin or humanized MoAb (palivizumab) was administered. All four LRTI patients showed a favorable clinical response, with 100% survival after a mean follow-up of 17 months (range [13][14][15][16][17][18][19][20][21][22][23][24]. With regard to IVIG, our guideline was not adhered to in two patients with severe LRTI-RSV who did not receive combined therapy with IVIG (episodes 1 and 6).…”

Successful prevention of respiratory syncytial virus nosocomial transmission following an enhanced seasonal infection control program

“…A more severe clinical course has been associated with early occurrence post-transplantation, chronic GVHD, persistant lymphopenia and allogeneic HSCT. [1][2][3][4][5][6][7][8] As preemptive therapy and treatment with aerosolized ribavirin and anti-RSV antibodies offer only modest benefits 1,[8][9][10][11][12][13][14] and no effective vaccine is currently available, recent strategies have focused on RSV infection prevention.…”