Strong Correlation between Serum Aspergillus Galactomannan Index and Outcome of Aspergillosis in Patients with Hematological Cancer: Clinical and Research Implications

Miceli, Marisa H.; Grazziutti, Monica; Woods, Gail L.; Zhao, Wei‐Li; Kocoglu, Mehmet H.; Barlogie, Bart; Anaissie, Elias

doi:10.1086/528714

Cited by 143 publications

(96 citation statements)

References 46 publications

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“…Success was defined in these studies as a repeatedly negative serum GM in the absence of new extrapulmonary lesions and failure as a persistently positive GM level or death within 2 weeks of GM normalization unless autopsy failed to show evidence of IA. A review of 27 studies of serial GM screening for the diagnosis of IA in hematologic malignancy and HSCT patients also found a correlation between GM levels in the week preceding IA outcome and clinical outcome (15). A simple correlation, however, is insufficient for establishing surrogacy; measurements that correlate with the outcome of interest are not useful surrogates unless they also capture the net effects of treatment on outcome (19,25).…”

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confidence: 99%

Prognostic Features of Galactomannan Antigenemia in Galactomannan-Positive Invasive Aspergillosis

et al. 2010

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Prognostic features of serum galactomannan (GM) remain poorly defined in patients with GM-positive invasive aspergillosis (GPA). We identified 93 patients with proven or probable invasive aspergillosis (IA) and GM values of >0.50 from January 2005 to March 2009. We used Cox modeling of time to 6-and 12-week mortality for the GM level at the time of diagnosis (GM 0 ), GM decay in the week following diagnosis in 72 patients with >2 GM values, other predictors of mortality, and antifungal use during the week following diagnosis. Six-week mortality was 55% in the whole cohort and 43% in patients with >2 GM determinations. The hazard ratio (HR) of GM 0 per unit increase and 1-week GM decay per unit decline per week were 1.25 (95% confidence interval [CI], 1.01 to 1.54; P ‫؍‬ 0.04) and 0.78 (95% CI, 0.63 to 0.96; P ‫؍‬ 0.02), respectively, adjusting for other predictors of IA mortality; these values remained stable after adjusting for antifungal use and were predictive of all-cause mortality at 12 weeks with similar adjusted HR values. We conclude that the combination of GM 0 and 1-week GM decay is predictive of all-cause mortality in patients with GPA, independent of other traditional risk factors for mortality and antifungal exposure, supporting GM decay as a potential surrogate endpoint for future antifungal therapeutic trials.Galactomannan (GM) is a cell wall polysaccharide released by growing Aspergillus hyphae (14,20). In experimental animal models of pulmonary invasive aspergillosis (IA), serum GM antigenemia correlates with tissue fungal burden, increasing with progressive disease and declining with effective antifungal therapy (1,2,6,12,16,17,24). In animal models, rising GM antigenemia has been associated with mortality, while clearance of antigenemia has been associated with survival (2,12,16,17).A similar relationship has been observed empirically in humans with IA. Soon after the development of serum GM testing, patients who died of IA were often noted to have progressively rising GM levels, while patients who survived IA gradually cleared their antigenemia (3,4,10,11,21,23). It has also been observed that the use of mold-active antifungal therapy blunts GM diagnostic sensitivity in this setting, as antigenemia declines below the diagnostic threshold with effective therapy (12, 13).Recently, two studies proposed a binarized GM outcome as a possible surrogate outcome measure for IA, based on a strong correlation between GM outcome and poor clinical outcomes in hematologic malignancy and hematopoietic stem cell transplantation (HSCT) patients (9, 27). Success was defined in these studies as a repeatedly negative serum GM in the absence of new extrapulmonary lesions and failure as a persistently positive GM level or death within 2 weeks of GM normalization unless autopsy failed to show evidence of IA. A review of 27 studies of serial GM screening for the diagnosis of IA in hematologic malignancy and HSCT patients also found a correlation between GM levels in the week preceding IA outcome and clinical outcome...

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Prognostic Features of Galactomannan Antigenemia in Galactomannan-Positive Invasive Aspergillosis

et al. 2010

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“…In this setting, the detection of positive results, particularly in two consecutive serum samples, provides strong support for the diagnosis of IA [von Eiff et al 1995;Mennick-Kersten and Verweij, 2006;Maertens et al 2001]. Recently, some authors have also suggested that GM could serve as a surrogate marker of clinical response to treatment in patients with IA [Miceli et al 2008;Maertens et al 2009;Boutboul et al 2002]. Several studies showed that the titer of GM tends to decrease in cases that demonstrated a clinical response.…”

Section: Therapeutic Advances In Infectious Disease 1 (3)mentioning

confidence: 93%

Invasive fungal infections in transplant recipients

Vázquez

Miceli

Alangaden

2013

Therapeutic Advances in Infection

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Invasive fungal infections are an important cause of morbidity and mortality in hematopoietic stem cell transplant and solid organ transplant recipients. Evolving transplant modalities and techniques, complex and extensive immunosuppressant strategies, and the increased use of broad spectrum antifungal prophylaxis has greatly impacted the epidemiology and temporal pattern of invasive fungal infections in the transplant population. The goal of this article is to provide an up-to-date review of the most commonly encountered invasive fungal infections seen in transplant recipients, including epidemiology, risk factors, clinical features, diagnostic dilemmas, management and their overall influence on outcomes.

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“…We and others recognize that more study is needed to better define the role of this biomarker, knowing that further confirmation of this strong correlation will have significant implications for patient management and clinical trial design. 24,25 …”

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confidence: 99%

Galactomannan serves as a surrogate endpoint for outcome of pulmonary invasive aspergillosis in neutropenic hematology patients

Maertens

Buvé

Theunissen

et al. 2009

Cancer

115

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BACKGROUND:A noninvasive, objective, reproducible, and quantitative Aspergillus‐specific surrogate marker is needed for a more accurate assessment of the outcome of invasive aspergillosis (IA) in patients with a hematologic disorder. The quantitative serum galactomannan index (GMI) assay seems to fulfill the requirements of surrogacy for outcome evaluation.METHODS:Kappa statistics were used to determine the strength of correlation between GMI outcome and clinical outcome (survival or death), autopsy data, and response outcome of IA in 70 adults with prolonged neutropenia. All patients underwent serial GMI monitoring until discharge or death.RESULTS:The overall correlation between GMI and clinical outcome was good at 6 weeks (κ = 0.5882; 95% confidence interval [95% CI], 0.4023‐0.7741) and was excellent at 12 weeks (κ = 0.8857; 95% CI, 0.7766‐0.9948). Concordance with autopsy findings was perfect (κ = 1). At 6 weeks, the correlation between GMI and response outcome (favorable or unfavorable) was excellent (κ = 0.7523; 95% CI, 0.5803‐0.9243). Survival was significantly better in patients who became GMI‐negative (P < .0001).CONCLUSIONS:In neutropenic patients with seropositive IA, serum galactomannan index outcome strongly correlates with survival, autopsy findings, and response outcome. This finding may have implications for patient management and for clinical trial design. Cancer 2009. © 2009 American Cancer Society.

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Strong Correlation between Serum Aspergillus Galactomannan Index and Outcome of Aspergillosis in Patients with Hematological Cancer: Clinical and Research Implications

Abstract: We conclude that serum GMI is a good marker of aspergillosis outcome.

Cited by 143 publications

References 46 publications

Prognostic Features of Galactomannan Antigenemia in Galactomannan-Positive Invasive Aspergillosis

Prognostic Features of Galactomannan Antigenemia in Galactomannan-Positive Invasive Aspergillosis

Invasive fungal infections in transplant recipients

Galactomannan serves as a surrogate endpoint for outcome of pulmonary invasive aspergillosis in neutropenic hematology patients

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