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Hill JA, Dalai SC, Hong DK, et al. Liquid Biopsy for Invasive Mold Infections in Hematopoietic Cell Transplant Recipients With Pneumonia Through Next-Generation Sequencing of Microbial Cell-Free DNA in Plasma. Clin Infect Dis. 2021;73(11):e3876-e3883doi: 10.1093/cid/ciaa1639.
Hill, J. A., Dalai, S. C., Hong, D. K., Ahmed, A. A., Ho, C., Hollemon, D., Blair, L., Maalouf, J., Keane-Candib, J., Stevens-Ayers, T., Boeckh, M., Blauwkamp, T. A., & Fisher, C. E. (2021). Liquid Biopsy for Invasive Mold Infections in Hematopoietic Cell Transplant Recipients With Pneumonia Through Next-Generation Sequencing of Microbial Cell-Free DNA in Plasma. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 73(11), e3876-e3883. https://doi.org/10.1093/cid/ciaa1639
Hill, Joshua A, et al. "Liquid Biopsy for Invasive Mold Infections in Hematopoietic Cell Transplant Recipients With Pneumonia Through Next-Generation Sequencing of Microbial Cell-Free DNA in Plasma." Clinical infectious diseases : an official publication of the Infectious Diseases Society of America vol. 73,11 (2021): e3876-e3883. doi: https://doi.org/10.1093/cid/ciaa1639
Hill JA, Dalai SC, Hong DK, Ahmed AA, Ho C, Hollemon D, Blair L, Maalouf J, Keane-Candib J, Stevens-Ayers T, Boeckh M, Blauwkamp TA, Fisher CE. Liquid Biopsy for Invasive Mold Infections in Hematopoietic Cell Transplant Recipients With Pneumonia Through Next-Generation Sequencing of Microbial Cell-Free DNA in Plasma. Clin Infect Dis. 2021 Dec 06;73(11):e3876-e3883. doi: 10.1093/cid/ciaa1639. PMID: 33119063; PMCID: PMC8664431.
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Clin Infect Dis. 2021 Dec 06;73(11):e3876-e3883. doi: 10.1093/cid/ciaa1639.

Liquid Biopsy for Invasive Mold Infections in Hematopoietic Cell Transplant Recipients With Pneumonia Through Next-Generation Sequencing of Microbial Cell-Free DNA in Plasma.

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

Joshua A Hill, Sudeb C Dalai, David K Hong, Asim A Ahmed, Carine Ho, Desiree Hollemon, Lily Blair, Joyce Maalouf, Jacob Keane-Candib, Terry Stevens-Ayers, Michael Boeckh, Timothy A Blauwkamp, Cynthia E Fisher

Affiliations

  1. Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
  2. University of Washington, Seattle, Washington, USA.
  3. Karius, Inc, Redwood City, California, USA.
  4. Stanford University School of Medicine, Stanford, California, USA.

PMID: 33119063 PMCID: PMC8664431 DOI: 10.1093/cid/ciaa1639

Abstract

BACKGROUND: Noninvasive diagnostic options are limited for invasive mold infections (IMIs). We evaluated the performance of a plasma microbial cell-free DNA sequencing (mcfDNA-Seq) test for diagnosing pulmonary IMI after hematopoietic cell transplant (HCT).

METHODS: We retrospectively assessed the diagnostic performance of plasma mcfDNA-Seq next-generation sequencing in 114 HCT recipients with pneumonia after HCT who had stored plasma obtained within 14 days of diagnosis of proven/probable Aspergillus IMI (n = 51), proven/probable non-Aspergillus IMI (n = 24), possible IMI (n = 20), and non-IMI controls (n = 19). Sequences were aligned to a database including >400 fungi. Organisms above a fixed significance threshold were reported.

RESULTS: Among 75 patients with proven/probable pulmonary IMI, mcfDNA-Seq detected ≥1 pathogenic mold in 38 patients (sensitivity, 51% [95% confidence interval {CI}, 39%-62%]). When restricted to samples obtained within 3 days of diagnosis, sensitivity increased to 61%. McfDNA-Seq had higher sensitivity for proven/probable non-Aspergillus IMI (sensitivity, 79% [95% CI, 56%-93%]) compared with Aspergillus IMI (sensitivity, 31% [95% CI, 19%-46%]). McfDNA-Seq also identified non-Aspergillus molds in an additional 7 patients in the Aspergillus subgroup and Aspergillus in 1 patient with possible IMI. Among 19 non-IMI pneumonia controls, mcfDNA-Seq was negative in all samples, suggesting a high specificity (95% CI, 82%-100%) and up to 100% positive predictive value (PPV) with estimated negative predictive values (NPVs) of 81%-99%. The mcfDNA-Seq assay was complementary to serum galactomannan index testing; in combination, they were positive in 84% of individuals with proven/probable pulmonary IMI.

CONCLUSIONS: Noninvasive mcfDNA-Seq had moderate sensitivity and high specificity, NPV, and PPV for pulmonary IMI after HCT, particularly for non-Aspergillus species.

© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: [email protected].

Keywords: Aspergillus ; HCT; cell-free DNA; mold; next-generation sequencing; pneumonia; transplant

References

  1. Clin Infect Dis. 2018 Oct 30;67(10):1610-1613 - PubMed
  2. Am J Clin Pathol. 2013 Jan;139(1):118-23 - PubMed
  3. Antimicrob Agents Chemother. 2019 Oct 22;63(11): - PubMed
  4. Nat Microbiol. 2019 Apr;4(4):663-674 - PubMed
  5. Clin Infect Dis. 2012 May;54(9):1322-31 - PubMed
  6. J Appl Lab Med. 2019 Jan;3(4):643-653 - PubMed
  7. Am J Respir Crit Care Med. 2019 Sep 1;200(5):535-550 - PubMed
  8. Clin Microbiol Infect. 2016 Jan;22(1):80-86 - PubMed
  9. Bone Marrow Transplant. 2012 Jun;47(6):846-54 - PubMed
  10. Biol Blood Marrow Transplant. 2016 Dec;22(12):2243-2249 - PubMed
  11. Lancet Infect Dis. 2013 Jun;13(6):519-28 - PubMed
  12. J Clin Microbiol. 2014 Oct;52(10):3731-42 - PubMed
  13. J Clin Microbiol. 2018 Sep 25;56(10): - PubMed
  14. Pediatr Blood Cancer. 2019 Jul;66(7):e27734 - PubMed
  15. Open Forum Infect Dis. 2018 Jul 31;5(8):ofy187 - PubMed
  16. Clin Infect Dis. 2013 May;56(10):e95-101 - PubMed
  17. Clin Infect Dis. 2016 Aug 15;63(4):e1-e60 - PubMed
  18. Expert Rev Mol Diagn. 2018 Oct;18(10):845-854 - PubMed
  19. Lancet Infect Dis. 2009 Feb;9(2):89-96 - PubMed
  20. Clin Infect Dis. 2009 Feb 1;48(3):265-73 - PubMed
  21. Clin Infect Dis. 2017 Jan 1;64(1):87-91 - PubMed
  22. Clin Microbiol Infect. 2016 Aug;22(8):670-80 - PubMed
  23. Clin Infect Dis. 2020 Sep 12;71(6):1367-1376 - PubMed
  24. Clin Infect Dis. 2015 Feb 1;60(3):405-14 - PubMed
  25. Clin Infect Dis. 2013 Aug;57(4):e22-e121 - PubMed
  26. Clin Infect Dis. 2008 Oct 15;47(8):1041-50 - PubMed
  27. Clin Infect Dis. 2015 Oct 15;61(8):1293-303 - PubMed
  28. Cochrane Database Syst Rev. 2015 Sep 07;(9):CD009551 - PubMed
  29. Diagn Microbiol Infect Dis. 2018 Nov;92(3):210-213 - PubMed
  30. Clin Infect Dis. 2012 Feb;54 Suppl 1:S23-34 - PubMed
  31. Open Forum Infect Dis. 2019 Aug 1;6(8): - PubMed
  32. Clin Infect Dis. 2008 Jun 15;46(12):1813-21 - PubMed
  33. Clin Infect Dis. 2018 Oct 30;67(10):1621-1630 - PubMed

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