Discussion

This case series describes three allogeneic HSCT recipients who developed RSV infection during the peri-transplant period and received combination therapy with oral ribavirin, IVIG, and palivizumab. No safety concerns were identified. Two patients with moderate- to high-risk disease according to the Immunodeficiency Scoring Index (ISI-RSV) achieved complete recovery, while one patient developed progressive respiratory failure and died despite aggressive therapy, likely due to mucormycosis. The heterogeneous clinical outcomes observed in these three cases—ranging from uncomplicated recovery to prolonged viral shedding and fatal respiratory failure—suggest that prognosis is determined primarily by host factors rather than RSV infection alone, despite all patients receiving identical combination therapy with oral ribavirin, IVIG, and palivizumab.

The adjunctive use of IVIG in respiratory viral infections remains controversial. Although IVIG and palivizumab have been employed in high-risk transplant recipients based on theoretical immunologic benefits, clinical evidence supporting their routine use is limited. All three patients in this series received IVIG and palivizumab in addition to ribavirin, hence the additional benefit of palivizumab could not be assessed.

The evidence regarding palivizumab as adjunctive treatment for RSV infection in immunocompromised patients remains limited and conflicting. In pediatric populations, clinical trials in heterogeneous groups showed no additional benefit, though studies in high-risk populations, including children with leukemia, demonstrated survival benefits [11], [12]. Among adults, palivizumab has been used successfully for RSV prevention during institutional outbreaks in HSCT recipients without safety concerns [13]. Additionally, palivizumab was initially invetigated as a therapeutic option in a phase−1 clinical trial in 2001 among pediatric and adult stem cell transplant recipients with no safety signal [14].

Several factors appeared to distinguish the two patients who recovered from the patient who ultimately died, although RSV infection occurred during the pre-engraftment period in all three cases. First factor, RSV-directed therapy was initiated earlier in the survivors. The interval from symptom onset or diagnosis to treatment was shorter for ribavirin (2 days vs. 3 days), IVIG (2–4 days vs. 8 days), and palivizumab (4 days vs. 8 days) in the surviving patients compared with the fatal case. While definitive conclusions cannot be drawn from such a small series, these observations raise the possibility that earlier initiation of RSV-specific therapy may contribute to improved outcomes, particularly in highly immunocompromised patients undergoing allogeneic HSCT. [5]

The second factor, the stage of RSV disease at the time of adjunctive therapies. The fatal case received palivizumab after already developing lower respiratory tract infection signs on chest imaging, while the two surviving cases still had upper respiratory tract infection. This would be consistent with the general principle that earlier intervention is more effective in viral respiratory infections, although it cannot be distinguished from differences in baseline disease severity in this series.

Third Factor, the route of palivizumab. While the FDA labeling among the pediatric age group remain as intramuscular [15], several case reports have successfully used the intervenous route among RSV infection [12], [13]. Interstingly, the two surviving cases have received the intravenous route, while the fatal case received the intramuscular route. This theoretically could be explained by the rapid nature of IV infusion and hence rapid effect, but it requires further study [16]. However, this factor remains speculative given the small number of cases. Fourth factor, the development of mucomycosis in the fatal case could explain the unfortunate outcome.

It is worth mentioning that the current descriptive nature of these cases these findings are exploratory and hypothesis-generating rather than evidence supporting earlier therapy or one administration route over another.

Moreover, these cases also highlight the challenge of interpreting RSV-directed therapies in HSCT recipients. Although ribavirin remains the most commonly utilized antiviral agent for RSV in transplant populations, evidence supporting its efficacy is derived largely from retrospective studies and observational cohorts [5]. Several studies suggest that early ribavirin therapy may reduce progression from URTI to LRTI and improve survival in high-risk patients, particularly when administered before respiratory failure develops [9]. However, optimal dosing, route of administration, and treatment duration remain uncertain. In our series, all patients received oral ribavirin, reflecting its practicality and increasing adoption as an alternative to aerosolized formulations.

Importantly, palivizumab was well tolerated in all three patients (two were intravanous route), with no infusion-related reactions, hypersensitivity events, or other treatment-attributable adverse effects observed following administration. These observations suggest that adjunctive palivizumab can be administered safely in highly immunocompromised HSCT recipients, although larger studies are needed to better characterize its safety and efficacy in this setting. To our knowledge, reports describing adjunctive palivizumab administered during the immediate peri-transplant period (day −7 to day +7) in adult allogeneic HSCT recipients are extremely limited.

This case series has several limitations. The small number of patients limits generalizability, the lack of comparative control, and the observational nature of the report precludes assessment of treatment efficacy. Moreover, the lack of viral load monitoring and objective immunophenotyping response impairs direct observation of the impact of monoclonal antibody. In addition, multiple concurrent infections and transplant-related complications, particularly in the third patient, make it difficult to determine the independent contribution of RSV to outcomes. Nevertheless, these cases provide real-world insight into the spectrum of RSV infection among patients undergoing allogeneic HSCT and highlight challenges encountered in contemporary transplant practice.