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Outcome of Human Parainfluenza Virus infection in allogeneic stem cell transplantation recipients: possible impact of ribavirin therapy

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Abstract

Background

This retrospective study focused on analyzing community-acquired respiratory virus (CARV) infections, in particular human parainfluenza virus (hPIV) after allogeneic stem cell transplant (allo-SCT) in adults recipients. It aimed to assess the impact of ribavirin treatment, clinical characteristics, and risk factors associated with lower respiratory tract disease (LRTD) progression and all-cause mortality.

Patients and methods

The study included 230 allo-SCT recipients diagnosed with hPIV between December 2013 and June 2023. Risk factors for the development of LRTD, disease severity, and mortality were analyzed. Ribavirin treatment was administered at physician discretion in 61 out of 230 cases (27%).

Results

Risk factors for LRTD progression in multivariate analysis were corticosteroids > 30 mg/day (Odds ratio (OR) 3.5, 95% Confidence Interval (C.I.) 1.3–9.4, p = 0.013), fever at the time of hPIV detection (OR 3.89, 95% C.I. 1.84–8.2, p < 0.001), and absolute lymphocyte count (ALC) < 0.2 × 109/L (OR 4.1, 95% C.I. 1.42–11.9, p = 0.009). In addition, the study found that ribavirin therapy significantly reduced progression to LRTD [OR 0.19, 95% C.I. 0.05–0.75, p = 0.018]. Co-infections (OR 5.7, 95% C.I. 1.4–23.5, p = 0.015) and ALC < 0.2 × 109/L (OR 17.7, 95% C.I. 3.6–87.1, p < 0.001) were independently associated with higher day + 100 after hPIV detection all-cause mortality. There were no significant differences in all-cause mortality and infectious mortality at day + 100 between the treated and untreated groups.

Conclusion

ALC, corticosteroids, and fever increased the risk for progression to LRTD while ribavirin decreased the risk. However, mortality was associated with ALC and co-infections. This study supports further research of ribavirin therapy for hPIV in the allo-HSCT setting.

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Data availability statement

Data available upon formal request by email to Jose Luis Piñana.

References

  1. Ustun C, Slabý J, Shanley RM, Vydra J, Smith AR, Wagner JE, et al. Human parainfluenza virus infection after hematopoietic stem cell transplantation: risk factors, management, mortality, and changes over time. Biol Blood Marrow Transplant. 2012;18:1580–8. https://doi.org/10.1016/j.bbmt.2012.04.012.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Kakiuchi S, Tsuji M, Nishimura H, Wang L, Takayama-Ito M, Kinoshita H, et al. Human parainfluenza virus type 3 infections in patients with hematopoietic stem cell transplants: the mode of nosocomial infections and prognosis. Jpn J Infect Dis. 2018;71:109–15.

    Article  CAS  PubMed  Google Scholar 

  3. Seo S, Xie H, Leisenring WM, Kuypers JM, Sahoo FT, Goyal S, Kimball LE, Campbell AP, Jerome KR, Englund JA, Boeckh M. Risk factors for parainfluenza virus lower respiratory tract disease after hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2019;25:163–71. https://doi.org/10.1016/j.bbmt.2018.08.021.

    Article  PubMed  Google Scholar 

  4. Nichols WG, Corey L, Gooley T, Davis C, Boeckh M. Parainfluenza virus infections after hematopoietic stem cell transplantation: risk factors, response to antiviral therapy, and effect on transplant outcome. Blood. 2001;98:573–8.

    Article  CAS  PubMed  Google Scholar 

  5. Chemaly RF, Ghosh S, Bodey GP, Rohatgi N, Safdar A, Keating MJ, et al. Respiratory viral infections in adults with hematologic malignancies and human stem cell transplantation recipients: a retrospective study at a major cancer center. Medicine (Baltimore). 2006;85:278–87.

    Article  PubMed  Google Scholar 

  6. D’Angelo CR, Kocherginsky M, Pisano J, Bishop MR, Godley LA, Kline J, et al. Incidence and predictors of respiratory viral infections by multiplex PCR in allogeneic hematopoietic cell transplant recipients 50 years and older including geriatric assessment. Leuk Lymphoma. 2016;57:1807–13.

    Article  CAS  PubMed  Google Scholar 

  7. Ljungman P, Ward KN, Crooks BN, Parker A, Martino R, Shaw PJ, et al. Respiratory virus infections after stem cell transplantation: a prospective study from the infectious diseases working party of the European Group for blood and marrow transplantation. Bone Marrow Transplant. 2001;28:479–84.

    Article  CAS  PubMed  Google Scholar 

  8. Renaud C, Campbell AP. Changing epidemiology of respiratory viral infections in hematopoietic cell transplant recipients and solid organ transplant recipients. Curr Opin Infect Dis. 2011;24:333–43. https://doi.org/10.1097/QCO.0b013e3283480440.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Shah DP, Shah PK, Azzi JM, Chemaly RF. Parainfluenza virus infections in hematopoietic cell transplant recipients and hematologic malignancy patients: a systematic review. Cancer Lett. 2016;370:358–64.

    Article  CAS  PubMed  Google Scholar 

  10. Srinivasan A, Wang C, Yang J, Shenep JL, Leung WH, Hayden RT. Symptomatic parainfluenza virus infections in children undergoing hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2011;17:1520–7.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Srinivasan A, Wang C, Yang J, Inaba H, Shenep JL, Leung WH, Hayden RT. Parainfluenza virus infections in children with hematologic malignancies. Pediatric Infect Dis J. 2011;30:855–9.

    Article  Google Scholar 

  12. Nichols WG, Gooley T, Boeckh M. Community-acquired respiratory syncytial virus and parainfluenza virus infections after hematopoietic stem cell transplantation: the Fred Hutchinson Cancer Research Center experience. Biol Blood Marrow Transplant. 2001;7:11S-15S.

    Article  PubMed  Google Scholar 

  13. Piñana JL, Pérez A, Chorão P, Guerreiro M, García-Cadenas I, Solano C, et al. Infectious Complications Subcommittee of the Spanish Hematopoietic Stem Cell Transplantation and Cell Therapy Group (GETH-TC). Respiratory virus infections after allogeneic stem cell transplantation: current understanding, knowledge gaps, and recent advances. Transpl Infect Dis. 2023;25: e14117. https://doi.org/10.1111/tid.14117.

    Article  CAS  PubMed  Google Scholar 

  14. Chemaly RF, Hanmod SS, Rathod DB, Ghantoji SS, Jiang Y, Doshi A, et al. The characteristics and outcomes of parainfluenza virus infections in 200 patients with leukemia or recipients of hematopoietic stem cell transplantation. Blood. 2012;119:2738–45 (quiz 2969).

    Article  CAS  PubMed  Google Scholar 

  15. Hirsch HH, Martino R, Ward KN, Boeckh M, Einsele H, Ljungman P. Fourth European Conference on Infections in Leukaemia (ECIL-4): guidelines for diagnosis and treatment of human respiratory syncytial virus, parainfluenza virus, metapneumovirus, rhinovirus, and coronavirus. Clin Infect Dis. 2013;56:258–66. https://doi.org/10.1093/cid/cis844.

    Article  PubMed  Google Scholar 

  16. Piñana JL, Pérez A, Montoro J, Hernani R, Lorenzo I, Giménez E, et al. The effect of timing on community acquired respiratory virus infection mortality during the first year after allogeneic hematopoietic stem cell transplantation: a prospective epidemiological survey. Bone Marrow Transplant. 2020;55:431–40. https://doi.org/10.1038/s41409-019-0698-7. (Epub 2019 Sep 24).

    Article  CAS  PubMed  Google Scholar 

  17. Piñana JL, Pérez A, Montoro J, Giménez E, Gómez MD, Lorenzo I, et al. Clinical effectiveness of influenza vaccination after allogeneic hematopoietic stem cell transplantation: a cross-sectional, prospective, observational study. Clin Infect Dis. 2019;68:1894–903. https://doi.org/10.1093/cid/ciy792.

    Article  CAS  PubMed  Google Scholar 

  18. Piñana JL, Hernández-Boluda JC, Calabuig M, Ballester I, Marín M, Madrid S, et al. A risk-adapted approach to treating respiratory syncytial virus and human parainfluenza virus in allogeneic stem cell transplantation recipients with oral ribavirin therapy: a pilot study. Transpl Infect Dis. 2017. https://doi.org/10.1111/tid.12729.

    Article  PubMed  Google Scholar 

  19. Shah DP, Ghantoji SS, Ariza-Heredia EJ, Shah JN, El Taoum KK, Shah PK, et al. Immunodeficiency scoring index to predict poor outcomes in hematopoietic cell transplant recipients with RSV infections. Blood. 2014;123:3263–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Seo S, Xie H, Campbell AP, Kuypers JM, Leisenring WM, Englund JA, et al. Parainfluenza virus lower respiratory tract disease after hematopoietic cell transplant: viral detection in the lung predicts outcome. Clin Infect Dis. 2014;58:1357–68.

    Article  PubMed  Google Scholar 

  21. Lefeuvre C, Salmona M, Bondeelle L, Houdouin V, Feghoul L, Jacquier H, et al. Frequent lower respiratory tract disease in hematological patients with parainfluenza virus type 3 infection. J Med Virol. 2021;93:6371–6. https://doi.org/10.1002/jmv.27243.

    Article  CAS  PubMed  Google Scholar 

  22. Tabatabai J, Schnitzler P, Prifert C, Schiller M, Weissbrich B, von Lilienfeld-Toal M, et al. Parainfluenza virus infections in patients with hematological malignancies or stem cell transplantation: analysis of clinical characteristics, nosocomial transmission and viral shedding. PLoS One. 2022;17: e0271756. https://doi.org/10.1371/journal.pone.0271756.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Marcolini JA, Malik S, Suki D, Whimbey E, Bodey GP. Respiratory disease due to parainfluenza virus in adult leukemia patients. Eur J Clin Microbiol Infect Dis. 2003;22:79–84.

    Article  CAS  PubMed  Google Scholar 

  24. Sidwell RW, Khare GP, Allen LB, Huffman JG, Witkowski JT, Simon LN, Robins RK. In vitro and in vivo effect of 1-β-d-ribofuranosyl-1,2,4-triazole-3-carboxamide (ribavirin) on types 1 and 3 parainfulenza virus infections. Chemotherapy. 1975;21:205–20.

    Article  CAS  PubMed  Google Scholar 

  25. Chakrabarti S, Avivi I, Mackinnon S, Ward K, Kottaridis PD, Osman H, Waldmann H, Hale G, Fegan CD, Yong K, Goldstone AH, Linch DC, Milligan DW. Respiratory virus infections in transplant recipients after reduced-intensity conditioning with Campath-1H: high incidence but low mortality. Br J Haematol. 2002;119:1125–32.

    Article  PubMed  Google Scholar 

  26. de Zwart AES, Riezebos-Brilman A, Alffenaar JC, van den Heuvel ER, Gan CT, van der Bij W, et al. Evaluation of 10 years of parainfluenza virus, human metapneumovirus, and respiratory syncytial virus infections in lung transplant recipients. Am J Transplant. 2020;20:3529–37. https://doi.org/10.1111/ajt.16073.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Stamouli M, Tsonis I, Gkirkas K, Economopoulou C, Siafakas N, Pournaras S, et al. Oral ribavirin is a highly effective treatment for lower respiratory tract infections due to respiratory syncytial virus or parainfluenza after allogeneic stem cell transplantation. Bone Marrow Transplant. 2021;56:511–3. https://doi.org/10.1038/s41409-020-01022-x.

    Article  PubMed  Google Scholar 

  28. Foolad F, Aitken SL, Shigle TL, Prayag A, Ghantoji S, Ariza-Heredia E, et al. Oral versus aerosolized ribavirin for the treatment of respiratory syncytial virus infections in hematopoietic cell transplant recipients. Clin Infect Dis. 2019;68:1641–9. https://doi.org/10.1093/cid/ciy760.

    Article  CAS  PubMed  Google Scholar 

  29. Salvatore M, Satlin MJ, Jacobs SE, Jenkins SG, Schuetz AN, Moss RB, et al. DAS181 for treatment of parainfluenza virus infections in hematopoietic stem cell transplant recipients at a single center. Biol Blood Marrow Transplant. 2016;22:965–70. https://doi.org/10.1016/j.bbmt.2016.02.011.

    Article  PubMed  Google Scholar 

  30. Aguayo-Hiraldo PI, Arasaratnam RJ, Tzannou I, Kuvalekar M, Lulla P, Naik S, et al. Characterizing the cellular immune response to parainfluenza virus 3. J Infect Dis. 2017;216:153–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Piñana JL, Xhaard A, Tridello G, Passweg J, Kozijn A, Polverelli N, et al. Seasonal human coronavirus respiratory tract infection in recipients of allogeneic hematopoietic stem cell transplantation. J Infect Dis. 2021;223:1564–75. https://doi.org/10.1093/infdis/jiaa553.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

Authors

Contributions

Authors responsible for the conception and the design of the study: Jose Luis Piñana and Ariadna Perez. Authors who performed the data analysis and generated the tables and figures: Jose Luis Piñana and Per Ljungman. Authors responsible for patient recruitment: José Luis Piñana, Juan Montoro, Ariadna Pérez, Pedro Chorão, Dolores Gómez, Manuel Guerreiro, Marta Villalba, and Rafael Hernani. Authors responsible for writing the manuscript: Jose Luis Piñana, Ariadna Perez, Per Ljungman, David Navarro, Dolores Gomez, Estela Gimenez and Carlos Solano were responsible for writing and supervising the writing of the manuscript. All co-authors were responsible for reviewing the analysis interpretation, suggesting modifications to the text, critically reviewing the manuscript, and for the final approval of the manuscript.

Corresponding author

Correspondence to José Luis Piñana.

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Conflict of interest

The author(s) declare that they have no conflicts of interest and have no funding resources to declare for this study.

Ethics approval statement

The local research ethics committee of the Hospital Clínico Universitario of Valencia approved the registry and study protocol (reference code 2019/351).

Patient consent statement

All patients included in this registry gave their signed informed consent in accordance with the declaration of Helsinki.

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Pérez, A., Montoro, J., Chorão, P. et al. Outcome of Human Parainfluenza Virus infection in allogeneic stem cell transplantation recipients: possible impact of ribavirin therapy. Infection (2024). https://doi.org/10.1007/s15010-024-02213-0

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