Introduction

Respiratory syncytial virus (RSV) infection represents a significant cause of morbidity and mortality in immunocompromised patients, particularly among hematopoietic stem cell transplant (HSCT) recipients during the early peri-transplantation period. The cumulative incidence of RSV infection in allogeneic HSCT recipients approaches 62% within the first year post-transplant, with progression to lower respiratory tract disease (LRTD) occurring in 7.6–39% of cases [1], [2]. RSV-associated mortality at 90–100 days post-detection ranges from 5.4% to 8.7% and increasing to 18% among patients who develop LRTD [1], [3]. Beyond acute mortality, RSV infection is associated with long-term pulmonary sequelae, including bronchiolitis obliterans syndrome and irreversible airflow obstruction, which contribute to substantial late mortality [2], [4].

The early peri-transplantation period represents a window of heightened vulnerability due to profound immunosuppression, lymphopenia, neutropenia, and the absence of protective adaptive immunity. Risk stratification tools such as the Immunodeficiency Scoring Index (ISI) and the Basel Severe Immunodeficiency grading have been developed to identify patients at the highest risk for progression to LRTD and death [1], [5]. High-risk ISI scores (7−12) are associated with four-fold increased risk of LRTD progression and significantly elevated mortality [1], [4].

Current therapeutic options for RSV in immunocompromised adults remain limited. Ribavirin, a nucleoside analog with broad antiviral activity, has been incorporated into selective management recommendations for adult allogeneic HSCT recipients, based on uncontrolled observational data [5]. Recent meta-analyses suggest that ribavirin may reduce all-cause mortality in patients with LRTD (pooled OR 0.19, 95% CI 0.07–0.51) and decrease progression to LRTD when administered as aerosolized therapy (pooled OR 0.27, 95% CI 0.09–0.80), though the certainty of evidence remains low to moderate [6]. Current guidelines recommend oral or intravenous ribavirin at 10–30 mg/kg/day (maximum 1800 mg/day) for allogeneic HSCT recipients with LRTD or those at high risk for progression, with prompt initiation at the early stage of upper respiratory tract infection viewed as potentially key to efficacy [5].

Palivizumab, a humanized monoclonal antibody targeting the RSV fusion protein, has been approved since 1998 for prophylaxis in high-risk pediatric populations but has limited data supporting its use in adults [7]. Its use in RSV prophylaxis has dramatically decreased after the approval of Nirsevimab, which provides expansion of use, longstanding protection, and lower cost [8], [9]. Current expert consensus from the 10th European Conference on Infections in Leukaemia discourages the use of palivizumab as primary, pre-exposure, or post-exposure prophylaxis in adults with hematological malignancies or undergoing HCT [5]. However, some experts consider palivizumab for severely immunosuppressed, hospitalized patients during nosocomial outbreaks, and its potential role as adjunctive therapy in combination with ribavirin for established RSV infection in high-risk adult patients remains incompletely defined [5].

Due to the critical outcome of the peri-transplant period, lack of established treatment protocols, the limited RSV specific antibody within commercially available IVIG, the addition of palivizumab was considreed and warranted investigations. The rationale for combination therapy with palivizumab and ribavirin is based on complementary mechanisms of action: ribavirin inhibits viral RNA synthesis, while palivizumab provides passive immunotherapy by neutralizing extracellular virus and preventing cell-to-cell spread.

This case series describes the clinical charactastistics of adult HSCT recipients who received adjunctive palivizumab with ribavirin and IVIG for RSV infection occurring during the early peri-transplantation period, a population at particularly high risk for severe disease and death.