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. 2015 Jun 11;125(24):3789-97.
doi: 10.1182/blood-2014-12-617035. Epub 2015 Apr 27.

Idiopathic pneumonia syndrome after hematopoietic cell transplantation: evidence of occult infectious etiologies

Sachiko Seo  1 , Christian Renaud  2 , Jane M Kuypers  3 , Charles Y Chiu  4 , Meei-Li Huang  3 , Erik Samayoa  4 , Hu Xie  5 , Guixia Yu  4 , Cynthia E Fisher  6 , Ted A Gooley  5 , Steven Miller  4 , Robert C Hackman  7 , David Myerson  8 , Ruth H Sedlak  9 , Yae-Jean Kim  10 , Takahiro Fukuda  11 , David N Fredricks  6 , David K Madtes  12 , Keith R Jerome  3 , Michael Boeckh  13
Affiliations

Idiopathic pneumonia syndrome after hematopoietic cell transplantation: evidence of occult infectious etiologies

Sachiko Seo et al. Blood. .

Abstract

Newer diagnostic methods may link more idiopathic pneumonia syndrome (IPS) cases to an infectious agent. Bronchoalveolar lavage (BAL) samples from 69 hematopoietic cell transplant (HCT) recipients with IPS diagnosed between 1992 and 2006 were tested for 28 pathogens (3 bacteria and 25 viruses) by quantitative polymerase chain reaction and for Aspergillus by galactomannan assay. Research BALs from 21 asymptomatic HCT patients served as controls. Among 69 HCT patients with IPS, 39 (56.5%) had a pathogen detected. The most frequent pathogens were human herpesvirus-6 (HHV-6) (N = 20 [29%]) followed by human rhinovirus (HRV), cytomegalovirus (CMV), and Aspergillus (N = 8 [12%] in each). HHV-6 and HRV were rarely detected in controls, whereas CMV and Aspergillus were occasionally detected with low pathogen load. Patients with pathogens had worse day-100 survival than those without (hazard ratio, 1.88; P = .03). Mortality in patients with only pathogens of "uncertain" significance in lung was similar to that in patients with pathogens of "established" significance. Metagenomic next-generation sequencing did not reveal additional significant pathogens. Our study demonstrated that approximately half of patients with IPS had pathogens detected in BAL, and pathogen detection was associated with increased mortality. Thus, an expanded infection detection panel can significantly increase the diagnostic precision for idiopathic pneumonia.

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Figures

Figure 1
Figure 1
Comparison of viral load between BAL and serum. (A) Viral load in samples from patients with DAH (N = 20). Each group indicates viral load in BAL (blue box) and serum (red box). P values are .002, .88, .002, and .30 in total, CMV, HHV-6, and others, respectively. (B) Viral load in samples from patients without DAH (N = 19). Each group indicates viral titer in BAL (blue box) and serum (red box). P values are .003, .66, .030, and .055 in total, CMV, HHV-6, and others, respectively.
Figure 2
Figure 2
Probability of overall survival and respiratory death by presence of pathogens. (A) Kaplan-Meier estimate of overall survival by presence of pathogens. One patient with ciHHV-6 was included in the IPS cases without pathogens. (B) Cumulative incidence of respiratory death by presence of pathogens. (C) Kaplan-Meier estimate of overall survival by pathogen type (aHR for established vs uncertain, 0.83 [0.41-1.69]; P = .61). (D) Cumulative incidence of respiratory death by pathogen type (aHR for established vs uncertain, 0.73 [0.33-1.61]; P = .44).
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References

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