The limited role of serum galactomannan assay in screening for invasive pulmonary aspergillosis in allogeneic stem cell transplantation recipients on micafungin prophylaxis: a retrospective study

Ryul Kim; Youngil Koh; Dong-Yeop Shin; Pyoeng Gyun Choe; Nam Joong Kim; Sung-soo Yoon; Myoung-don Oh; Wan Beom Park; Inho Kim

doi:10.5045/br.2017.52.4.300

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Original Article

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Blood Res 2017; 52(4):

Published online December 26, 2017

https://doi.org/10.5045/br.2017.52.4.300

The limited role of serum galactomannan assay in screening for invasive pulmonary aspergillosis in allogeneic stem cell transplantation recipients on micafungin prophylaxis: a retrospective study

Ryul Kim¹, Youngil Koh^1,2, Dong-Yeop Shin^1,2, Pyoeng Gyun Choe¹, Nam Joong Kim¹, Sung-soo Yoon^1,2, Myoung-don Oh¹, Wan Beom Park^1,#*, and Inho Kim^1,2,#*

Author Info. +

¹Department of Internal Medicine, Seoul National University, College of Medicine, Seoul, Korea.

²Cancer Research Institute, Seoul National University, College of Medicine, Seoul, Korea.

Correspondence to : Wan Beom Park. M.D. Department of Internal Medicine, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul 03080, Korea. wbpark1@snu.ac.kr

Received: July 14, 2017; Revised: August 14, 2017; Accepted: October 25, 2017

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

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Abstract

Background

We evaluated the outcomes of serum galactomannan (GM) assay for the screening of invasive pulmonary aspergillosis (IPA) in allogeneic hematopoietic stem cell transplantation (alloHSCT) recipients while on primary antifungal prophylaxis (PAP).

Methods

This study included patients with hematologic disorders who underwent alloHSCT from January 2013 to November 2015. Patients received routine PAP with fluconazole before 2014 and micafungin after 2014; serum GM tests were performed and retrospectively analyzed. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of serum GM tests for detection of probable/proven IPA were evaluated. The serial change of serum GM levels was illustrated on a time series plot.

Results

A total of 136 alloHSCT recipients at Seoul National University Hospital were included in the study. Fluconazole was administered in 72 patients for PAP, while micafungin was administered in the remaining 64 patients. The overall sensitivity, specificity, and NPV of serum GM assays were 95.8% (95% confidence interval [CI] 78.9?99.9%), 93.8% (95% CI 91.7?95.5%), and 99.8% (95% CI 99.1?100.0%), respectively. However, the PPV of GM tests was relatively low at 35.4% (95% CI 23.9?48.2%). The serial change in serum GM levels differed according to the antifungal agents used. With effective PAP using micafungin, serial serum GM levels showed zero order kinetics during the neutropenic period.

Conclusion

Although the serum GM assay is a sensitive and specific test for detecting IPA in alloHSCT recipients, its role for routine surveillance in an era of effective PAP with micafungin is limited.

Keywords Hematology, Stem cell transplantation, Galactomannan, Invasive pulmonary aspergillosis, Antifungal prophylaxis

Article

Original Article

Blood Res 2017; 52(4): 300-306

Published online December 26, 2017 https://doi.org/10.5045/br.2017.52.4.300

The limited role of serum galactomannan assay in screening for invasive pulmonary aspergillosis in allogeneic stem cell transplantation recipients on micafungin prophylaxis: a retrospective study

Ryul Kim¹, Youngil Koh^1,2, Dong-Yeop Shin^1,2, Pyoeng Gyun Choe¹, Nam Joong Kim¹, Sung-soo Yoon^1,2, Myoung-don Oh¹, Wan Beom Park^1,#*, and Inho Kim^1,2,#*

¹Department of Internal Medicine, Seoul National University, College of Medicine, Seoul, Korea.

²Cancer Research Institute, Seoul National University, College of Medicine, Seoul, Korea.

Correspondence to:Wan Beom Park. M.D. Department of Internal Medicine, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul 03080, Korea. wbpark1@snu.ac.kr

Received: July 14, 2017; Revised: August 14, 2017; Accepted: October 25, 2017

Abstract

Background

Methods

Results

Conclusion

Although the serum GM assay is a sensitive and specific test for detecting IPA in alloHSCT recipients, its role for routine surveillance in an era of effective PAP with micafungin is limited.

Keywords: Hematology, Stem cell transplantation, Galactomannan, Invasive pulmonary aspergillosis, Antifungal prophylaxis

Abstract

Fig 1.

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Figure 1.

Classification of a total of 698 serum galactomannan tests. A total of 423 tests were performed using fluconazole as PAP, while micafungin was administered when the remaining 275 tests were performed. Each serum GM assays were further divided according to goal of the assay: routine surveillance and diagnostic workup for infection.

Blood Research 2017; 52: 300-306https://doi.org/10.5045/br.2017.52.4.300

Fig 2.

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Figure 2.

Time series plots of serum galactomannan optical density (OD) index under (A) fluconazole prophylaxis and (B) micafungin prophylaxis.

Blood Research 2017; 52: 300-306https://doi.org/10.5045/br.2017.52.4.300

Table 1 . Baseline characteristics of hematology patients receiving allogeneic hematopoietic stem cell transplantation (N=136)..

^a)Fisher's exact test..

Abbreviations: HSCT, hematopoietic stem cell transplantation; GM, galactomannan; N, number of patients..

Table 2 . The diagnostic performance of serum galactomannan (GM) assays. A total of 698 serum GM assays, and four subgroups classified according to antifungal agents (fluconazole vs. micafungin) and the goal of test (surveillance vs. diagnostic workup)..

Abbreviations: F-GM_diag, fluconazole PAP with GM assay for diagnostic workup; F-GM_surv, fluconazole PAP with GM assay for surveillance; IPA, invasive pulmonary aspergillosis; M-GM_diag, micafungin PAP with GM assay for diagnostic workup; M-GM_surv, micafungin PAP with GM assay for surveillance; NA, not available; NPV, negative predictive value; PPV, positive predictive value..