Oral Ribavirin for the Treatment of Respiratory Syncytial Virus Infection in Allogeneic Stem Cell Transplant Recipients-Utility of the Immunodeficiency Scoring Index for Risk Stratification

Background: Respiratory syncytial virus (RSV) infection is a serious complication post allogeneic stem cell transplant. Aerosolized ribavirin is a commonly used therapy; however, oral ribavirin is an alternative with many advantages. There is paucity in literature regarding treatment outcomes using the oral form. Recently, the immunodeficiency scoring index (ISI) was derived from the largest reported RSV cohort to date using aerosolized ribavirin.

Objectives: We sought to investigate whether the ISI is predictive of mortality and lower respiratory tract infection (LRTI) progression in an independent cohort of RSV infected allogeneic transplant recipients treated with oral ribavirin therapy.

Methods: Consecutive patients diagnosed with RSV infection seen at Mayo Clinic Rochester from 2008 – 2014 were identified. Clinical and pathologic data were retrospectively abstracted after obtaining IRB approval. The ISI (Blood 2014) score was calculated for each patient. Survival estimates were done using the Kaplan-Meier method and log rank test was used to compare the risk groups.

Results: A total of 53 patients tested positive for RSV infection. Twenty eight were female (53%) and the median age at RSV infection was 55 years (range 15-71). Stem cell source was peripheral blood in 44 (83%), 7 bone marrow (13%) and 2 were double cord (4%). Indication for transplant was myeloid malignancy in 34 patients (64%), lymphoid malignancy in 16 (30%) and plasma cell dyscrasia in 3 (6%). Sixteen (30%) had myeloablative conditioning. Median time from onset of symptoms to diagnosis was 2 days (0-15) and median time from transplant to diagnosis was 11 months (0-48). Twenty eight patients (53%) had URTI symptoms at presentation, 11 (21%) had LRTI and 14 (26%) had progression from URTI to LRTI. Stratifying per the ISI criteria, 16 patients (30%) were low risk, 31 (59%) were moderate and 6 (11%) were high risk. Median survival post RSV diagnosis was 17 months (0-78). Forty six patients received oral ribavirin, 4 received aerosolized ribavirin and 3 were not treated. Five patients (3 high and 2 moderate risk) had RSV associated mortality with a median time to death of 8 days (7-18) due to respiratory failure and/or acute respiratory distress syndrome. Case fatality among high, moderate and low risk patients were 50%, 6% and 0%, respectively. Overall survival was statistically significant among the risk groups (P 0.0112). Predicting LRTI at diagnosis and risk of URTI to LRTI progression was however not significant (P 0.1375 and 0.4505, respectively).

Conclusion: Use of oral ribavirin in low and moderate risk patients was associated with an excellent outcome. The ISI predicted survival but not risk of LRTI post RSV infection in an independent cohort of allogeneic stem cell transplant recipients treated with oral ribavirin. Elevated case fatality in high risk cases highlights the need for better therapies in this group of patients.