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Novel factors to predict respiratory viral disease progression in allogeneic hematopoietic cell transplant recipients

Bone Marrow Transplantation volume 57, pages 649–657 (2022)Cite this article

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A Correction to this article was published on 11 October 2024

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Abstract

We assessed novel factors and the immunodeficiency scoring index (ISI) to predict progression to lower respiratory tract infection (LRTI) among hematopoietic cell transplant (HCT) recipients presenting with upper respiratory tract infection (URTI) with 12 viruses in the PCR era. We retrospectively analyzed the first respiratory virus detected by multiplex PCR in allogeneic HCT recipients (4/2008–9/2018). We used Cox proportional hazards models to examine factors for progression to LRTI within 90 days among patients presenting with URTI. A total of 1027 patients (216 children and 811 adults) presented with URTI only. Among these, 189 (18%) progressed to LRTI (median: 12 days). Multivariable models demonstrated a history of  >1 transplant, age  ≥40 years, time post-HCT (≤30 days), systemic steroids, hypoalbuminemia, hyperglycemia, cytopenia, and high ISI (scores 7–12) were associated with an increased risk of progression to LRTI. Respiratory syncytial virus and human metapneumovirus showed the highest progression risk. Patients with ≥3 independent risk factors or high ISI scores were highly likely to progress to LRTI. We identified novel risk factors for progression to LRTI, including history of multiple transplants and hyperglycemia, suggesting an intervention opportunity with glycemic control. ISI and number of risk factors appear to predict disease progression across several viruses.

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Fig. 1: Incidence of progression to LRTI and overall incidence of LRTI.
Fig. 2: Multivariable Cox proportional hazards models for progression to viral LRTI including immunodeficiency scoring index.
Fig. 3: Cumulative incidence of progression to LRTI within 90 days among patients presenting with URTI by virus type, stratified by immunodeficiency scoring index as well as number of risk factors.
Fig. 4: Multivariable Cox proportional hazards models for progression to viral LRTI without immunodeficiency scoring index.

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Acknowledgements

We thank Lucy Maher, Daniela Ramos, and Sydnee Dismuke for data collection and Chris Davis and Ryan Basom for database services.

Funding

This work was supported by the National Institutes of Health (grant numbers K23AI139385 to CO, R01HL081595, and K24HL093294 to MB, CA18029 to WL, clinical database, CA15704 to HX); the Fred Hutchinson Cancer Research Center Vaccine and Infectious Disease Division (biorepository); Seattle Children’s Research Institute Clinical Research Scholars Program Award) to CO.

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Author notes

  1. Chikara Ogimi

    Present address: Pediatric Infectious Diseases, National Center for Child Health and Development, Tokyo, Japan

Authors and Affiliations

  1. Pediatric Infectious Diseases Division, Seattle Children’s Hospital, Seattle, WA, USA

    Chikara Ogimi, Alpana Waghmare & Janet A. Englund

  2. Department of Pediatrics, University of Washington, Seattle, WA, USA

    Chikara Ogimi, Alpana Waghmare, Paul A. Carpenter & Janet A. Englund

  3. Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    Chikara Ogimi, Alpana Waghmare, Keith R. Jerome & Michael Boeckh

  4. Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    Hu Xie, Wendy M. Leisenring, Masumi Ueda Oshima, Paul A. Carpenter & Michael Boeckh

  5. Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA

    Keith R. Jerome

  6. Division of Medical Oncology, University of Washington, Seattle, WA, USA

    Masumi Ueda Oshima

  7. Pediatric Hematology Oncology, Seattle Children’s Hospital, Seattle, WA, USA

    Paul A. Carpenter

  8. Department of Medicine, University of Washington, Seattle, WA, USA

    Michael Boeckh

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Contributions

CO designed this study, assisted in the analysis, interpreted results, and wrote the paper; HX and WML performed the statistical analysis and wrote the paper; AW, MU, and PAC provided clinical input, interpretation of results, and reviewed the paper; KRJ provided technical oversight for laboratory, and reviewed the paper; JAE and MB provided oversight, designed this study, interpreted results, and reviewed the paper.

Corresponding author

Correspondence to Chikara Ogimi.

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Competing interests

AW reports grant support from Ansun Biopharma, Allovir, VB Tech, Amazon, Inc, GlaxoSmithKline and Pfizer, and is an Advisory Board Member for Kyorin Pharmaceutical. JAE reports grant support from AstraZeneca, Merck, Pfizer, GlaxoSmithKline and Novavax, is an Advisory Board Member and consultant for Sanofi Pasteur, and is a consultant for Meissa Vaccines. MB reports grant support from Amazon, GSK, Regeneron, Janssen, Gilead and VirBio; he is a consultant for Allovir, Janssen, Gilead, ReViral and VirBio, and an Advisory Board Member for Evrys Bio (option to purchase shares). All other authors report no potential conflicts. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

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The original online version of this article was revised: The legend of Fig. 3 and the Supplementary Information has been corrected.

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Ogimi, C., Xie, H., Waghmare, A. et al. Novel factors to predict respiratory viral disease progression in allogeneic hematopoietic cell transplant recipients. Bone Marrow Transplant 57, 649–657 (2022). https://doi.org/10.1038/s41409-022-01575-z

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