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Predicting risk of progression to lower respiratory tract infection in allogeneic hematopoietic cell transplant recipients with respiratory viral infections: where are we now?

Bone Marrow Transplantation volume 57, pages 701–702 (2022)Cite this article

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In this issue of Bone Marrow Transplantation, Ogimi and colleagues report on a large cohort of 1027 allogeneic hematopoietic cell transplant (HCT) recipients from a single center infected with respiratory viruses (excluding severe acute respiratory syndrome coronavirus 2 or SARS-CoV-2) to identify risk factors for progression to lower respiratory tract infection (LRTI). The authors evaluated in their cohort the use of the Immunodeficiency Scoring Index (ISI) [1], a combination of different predictors of LRTI, in addition to risk factors such as hyperglycemia and hypoalbuminemia. Prior studies identified lymphopenia, neutropenia, age, time from transplantation, exposure to steroids, graft-versus-host disease, prior autologous HCT, smoking history, and type of transplant as risk factors for progression to an LRTI [2]. Our group developed the ISI for respiratory syncytial virus (RSV) that combines seven major risk factors to predict the rate of LRTI in allogeneic HCT recipients in a large cohort (n = 237) [1]. The ISI assigns a weighted score to each risk factor based on its adjusted hazard ratio. These factors include neutropenia (absolute neutrophil count <500/μl), lymphocytopenia (absolute lymphocyte count <200/μl), patient age of at least 40 years, use of a myeloablative conditioning regimen, acute or chronic graft-versus-host disease, use of corticosteroids within 30 days of RSV infection, and transplantation within 30 days of or in the pre-engraftment period during RSV infection [1]. This quantifiable ISI stratifies patients into low-risk (0–2), moderate-risk [3,4,5,6], and high-risk (≥7) categories regarding progression or death. Studies have validated the ISI for different respiratory viral infections in allogeneic and autologous HCT recipients at multiple centers with varying success [2,3,4,5,6].

In addition to a high ISI score (≥7), Ogimi and colleagues identified factors not reported before in multivariate models, such as hypoalbuminemia (<3 g/dL), more than one HCT prior to infection, and hyperglycemia (peak glucose level >200 mg/dl), with the highest risk for progression to LRTI in patients with RSV and metapneumovirus infections. Notably, some of these factors are potentially modifiable, such as hyperglycemia and hypoalbuminemia. Not surprisingly, influenza infection was not associated with significant progression to LRTI in their analysis, as therapy with a neuraminidase inhibitor such as oseltamivir may have altered the course of the infection. In a previous study, we showed that early therapy (within 48 h of symptom onset) with oseltamivir was associated with decreased rates of LRTI and death regardless of the ISI score [7]. Influenza vaccines in allogeneic HCT recipients may also impact outcomes, but this remains to be determined in future studies [7]. The variable definitions in this study were consistent with those in prior studies by their group and others [6, 8, 9], including LRTI and lymphopenia. The Use of consistent variable definitions across studies increases the reliability of quantitative models like the ISI score in predicting outcomes from respiratory viral infections, which will lead to better design and planning of future clinical trials in this patient population.

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References

  1. 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  Google Scholar 

  2. Khawaja F, Chemaly RF. Respiratory syncytial virus in hematopoietic cell transplant recipients and patients with hematologic malignancies. Haematologica. 2019;104:1322–31.

    Article  CAS  Google Scholar 

  3. Kmeid J, Vanichanan J, Shah DP, El Chaer F, Azzi J, Ariza-Heredia EJ, et al. Outcomes of Influenza Infections in Hematopoietic Cell Transplant Recipients: Application of an Immunodeficiency Scoring Index. Biol Blood Marrow Transpl. 2016;22:542–8.

    Article  Google Scholar 

  4. Ljungman P, de la Camara R, Mikulska M, Tridello G, Aguado B, Zahrani MA, et al. COVID-19 and stem cell transplantation; results from an EBMT and GETH multicenter prospective survey. Leukemia. 2021;35:2885–94.

    Article  CAS  Google Scholar 

  5. Houist AL, Bondeelle L, Salmona M, LeGoff J, de Latour RP, Rivière F, et al. Evaluation of prognostic scores for respiratory syncytial virus infection in a French multicentre cohort of allogeneic haematopoietic stem cell transplantation recipients. Bone Marrow Transpl. 2021;56:3032–41.

    Article  Google Scholar 

  6. Ogimi C, Xie H, Waghmare A, Ueda Oshima M, Mallhi KK, Jerome KR, et al. Risk factors for seasonal human coronavirus lower respiratory tract infection after hematopoietic cell transplantation. Blood Adv. 2021;5:1903–14.

    Article  CAS  Google Scholar 

  7. Kumar D, Ferreira VH, Blumberg E, Silveira F, Cordero E, Perez-Romero P, et al. A 5-Year Prospective Multicenter Evaluation of Influenza Infection in Transplant Recipients. Clin Infect Dis. 2018;67:1322–9.

    Article  Google Scholar 

  8. Seo S, Xie H, Leisenring WM, Kuypers JM, Sahoo FT, Goyal S, et al. Risk Factors for Parainfluenza Virus Lower Respiratory Tract Disease after Hematopoietic Cell Transplantation. Biol Blood Marrow Transpl. 2019;25:163–71.

    Article  Google Scholar 

  9. Ogimi C, Waghmare AA, Kuypers JM, Xie H, Yeung CC, Leisenring WM, et al. Clinical Significance of Human Coronavirus in Bronchoalveolar Lavage Samples From Hematopoietic Cell Transplant Recipients and Patients With Hematologic Malignancies. Clin Infect Dis. 2017;64:1532–9.

    Article  CAS  Google Scholar 

  10. 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.

    Article  CAS  Google Scholar 

  11. Treanor JJ, Hayden FG, Vrooman PS, Barbarash R, Bettis R, Riff D, et al. Efficacy and safety of the oral neuraminidase inhibitor oseltamivir in treating acute influenza: a randomized controlled trial. US Oral Neuraminidase Study Group. JAMA. 2000;283:1016–24.

    Article  CAS  Google Scholar 

  12. Oboho IK, Reed C, Gargiullo P, Leon M, Aragon D, Meek J, et al. Benefit of Early Initiation of Influenza Antiviral Treatment to Pregnant Women Hospitalized With Laboratory-Confirmed Influenza. J Infect Dis. 2016;214:507–15.

    Article  Google Scholar 

  13. Jayk Bernal A, Gomes da Silva MM, Musungaie DB, Kovalchuk E, Gonzalez A, Delos Reyes V, et al. Molnupiravir for Oral Treatment of Covid-19 in Nonhospitalized Patients. N Engl J Med. 2022;386:509–20.

    Article  Google Scholar 

  14. Chemaly RF, Dadwal SS, Bergeron A, Ljungman P, Kim Y-J, Cheng G-S, et al. A Phase 2, Randomized, Double-blind, Placebo-Controlled Trial of Presatovir for the Treatment of Respiratory Syncytial Virus Upper Respiratory Tract Infection in Hematopoietic-Cell Transplant Recipients. Clin Infect Dis. 2020;71:2777–86.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Infectious Diseases, Infection Control and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Fareed Khawaja & Roy F. Chemaly

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  1. Fareed Khawaja
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Both RFC and FK contributed equally to this manuscript.

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Correspondence to Roy F. Chemaly.

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Competing interests

RFC serves a scientific consultant/adviser for Merck, Ansun Biopharma, Takeda/Shire, Oxford Immunotec, ADMA Biologics, Pulmotec, Enanta, ReViral, and Genentech, and received research funding from Merck, Takeda/Shire, Oxford Immunotec, AiCuris, Ansun Biopharma, Viracor, Karius, Genentech, and Janssen. FK has none to report.

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Khawaja, F., Chemaly, R.F. Predicting risk of progression to lower respiratory tract infection in allogeneic hematopoietic cell transplant recipients with respiratory viral infections: where are we now?. Bone Marrow Transplant 57, 701–702 (2022). https://doi.org/10.1038/s41409-022-01616-7

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