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

Abstract

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

Respiratory syncytial virus infection following hematopoietic stem cell transplantation

“…[9][10][11][12][13] Unlike the outcome in the autologous transplant patients 14 reported by Anaissie and colleagues, five of the six autologous transplant recipients in our series diagnosed with an RSV URI in the early transplant period, developed pneumonia, which required mechanical ventilation in three. Although all five patients ultimately cleared the virus, two patients died of respiratory failure 29 and 45 days, respectively, post transplant.…”

“…[9][10][11][12] Although treatment with aerosolized ribavirin and/or intravenous gammaglobulin (IVIG) can prevent pneumonia in approximately 70% of patients with RSV-associated URTD post HSCT, mortality remains high in patients who develop pneumonia despite prophylaxis. 12,13 Due to the variable outcome of RSV-associated respiratory infections post HSCT reported in the literature to date, [9][10][11][12][13][14] we conducted a retrospective observational study to determine the incidence of RSV infection among children and adults following allogeneic (related and unrelated) or autologous HSCT performed at the Memorial SloanKettering Cancer Center between 1 January 1994 and 31 December 1999. We also describe the clinical presentation and outcome of pre-transplant and incident RSV-associated respiratory infections among HSCT recipients.…”

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.…”

Pre-emptive oral ribavirin therapy of paramyxovirus infections after haematopoietic stem cell transplantation: a pilot study

“…The difficulty in delivering aerosolised ribavirin, compounded by patient discomfort and the financial burden, makes widespread acceptance of this approach unlikely. 10 Moreover, in the absence of randomised studies, the clinical benefit from such an approach remains unsubstantiated.…”