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Serum galactomannan surveillance may be safely withdrawn from antifungal management of hematology patients on effective antimold prophylaxis: a pilot single-center study

Bone Marrow Transplantation volume 52, pages 326–329 (2017)Cite this article

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Pretest prevalence of infection is a key driver of the performance of diagnostic tests,1, 2 including the serum galactomannan (sGM) assay for invasive aspergillosis (IA).3, 4 The use of effective antimold prophylaxis (EAMP) with posaconazole in high-risk hematology patients with AML and allogeneic hematopoietic cell transplantation (HCT) successfully reduces the incidence of IA.5, 6, 7, 8 Thus, pre-emptive twice weekly sGM-based surveillance of asymptomatic patients on EAMP becomes unreliable, as the low pretest prevalence of infection and therefore, the low positive predictive value of the test in this context limit its clinical utility and may mislead diagnostic and therapeutic efforts.9 However, the diagnostic accuracy of the sGM test remains high when applied as part of a thorough diagnostic-driven algorithm.9 This evidence would suggest that antifungal diagnostic management of high-risk hematology patients on EAMP should move from universal surveillance to a diagnostic-driven strategy only for symptomatic cases with a clinical suspicion of invasive fungal disease (IFD).9, 10

Here, we report a prospective clinical study in high-risk hematology patients on posaconazole prophylaxis assessing the feasibility, safety and efficiency of discontinuing twice weekly sGM surveillance from our antifungal management strategy. The assay continued to be used only for diagnostic purposes in all patients with persistent fever over 72 h unresponsive to broad-spectrum antibiotics and those with a clinical suspicion of IFD. Other than the discontinuation of sGM surveillance, our antifungal practice and study characteristics remained as previously described with the pre-emptive surveillance strategy.9 The endpoints to assess the effectiveness, safety and efficiency of this change in management are the incidence of probable and proven IA and IFD as revised by the European Organization for Research and treatment of Cancer and the Mycoses Study Group (EORTC/MSG),11 the occurrence and reasons for prophylaxis discontinuation and replacement with antifungal treatment, all-cause mortality, cause of death during the risk episodes and the impact on the use of diagnostics tests. The study includes data on three different cohorts of high-risk episodes under posaconazole primary antifungal prophylaxis: patients with AML and prolonged neutropenia after chemotherapy (AML chemotherapy episodes) who started posaconazole prophylaxis 24 h after the last day of chemotherapy until neutrophil recovery >0.5 × 109/L, allogeneic HCT recipients (allogeneic HCT episodes), receiving prophylaxis from day 1 after hematopoietic cell infusion and up to day 100, and transplant recipients with GvHD (GvHD episodes), who received posaconazole from the start of ⩾1 mg/kg of daily corticosteroids until tapering to <10 mg of daily prednisone or equivalent. Along with sGM testing, our IFD diagnostic algorithm included computed tomographic (CT) scans, bronchoscopy and bronchoalveolar lavage with GM and additional samples for bacterial, fungal and viral microbiology in case of any pulmonary infiltrates, as well as additional cultures from blood, sputum or other relevant samples when clinically indicated. Further details on isolation measures, antifungal treatment recommendations, and other anti-microbial prophylaxis and management have been previously described.8, 9 Posaconazole oral solution was administered following the drug’s prescribing information (https://www.merckconnect.com/noxafil/prescribing-information.html). sGM tests (Platelia Aspergillus enzyme immunoassay, Bio-Rad Laboratories, Madrid, Spain) were considered positive for an optical index ⩾0.7 in one sample or ⩾0.5 in two consecutive samples. Episodes with positive sGM tests results were defined as false positive on clinical grounds if patients did not develop any other criteria of probable or proven IFD, survived the episode and remained on posaconazole prophylaxis throughout without receiving other antifungal therapy.9 While the definition of IFD for end-point analysis follows EORTC/MSG criteria,11 the clinical decisions to replace posaconazole prophylaxis with antifungal therapy relied in all cases on an individualized clinical judgment, including patient general condition, signs and symptoms, test results and treatment compliance, rather than on the fulfillment of EORTC/MSG criteria.9 Our ethics committee approved the study (CEIC Bellvitge), patients signed informed consents for treatment and data collection, and study data were recorded in a specific database. Software package SPSS (version 17; http://www.spss.com) was used for statistical analysis. Descriptive and comparative analyses were done, with Fisher’s exact test or chi-square analysis for differences in proportions, and variance analysis or non-parametric tests for differences between GM results. P-values are two-sided and considered statistically significant if <0.05.

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Acknowledgements

This study was partly supported by an unrestricted research grant from Schering Plough.

Author contributions

RFD, ISO and MCE are responsible for the conception and design of the study and wrote the initial draft of this manuscript. All authors contributed to the execution of the study, the analysis and/or interpretation of the data, reviewed the manuscript content and approved the manuscript for publication.

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Author notes

  1. R F Duarte and I Sánchez-Ortega: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Hematology, Catalan Institute of Oncology–Hospital Duran i Reynals, Biomedical Research Institute of Bellvitge (Idibell), Barcelona, Spain

    R F Duarte, I Sánchez-Ortega, M Arnan, B Patiño & A Sureda

  2. Department of Microbiology, Hospital Universitario de Bellvitge, Barcelona, Spain

    J Ayats

  3. Department of Micology, Centro Nacional de Microbiología–Instituto de Salud Carlos III, Madrid, Spain

    M Cuenca-Estrella

Authors
  1. R F Duarte
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  4. B Patiño
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Correspondence to R F Duarte.

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Competing interests

MA, RFD and ISO have received consultation and/or speaker fees from Esteve, Gilead Science, Merck Sharp & Dohme, Pfizer and/or Schering Plough during the study period. MCE has received grant support from Astellas Pharma, bioMerieux, Gilead Sciences, Merck Sharp and Dohme, Pfizer, Schering Plough, Soria Melguizo SA and Ferrer International, has been an advisor/consultant to Astellas Pharma, Gilead Sciences, Merck Sharp and Dohme, Pfizer and Schering Plough, and has received honoraria for talks on behalf of Gilead Sciences, Merck Sharp and Dohme, Pfizer, Astellas Pharma and Schering Plough. The remaining authors declare no conflict of interest.

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Duarte, R., Sánchez-Ortega, I., Arnan, M. et al. Serum galactomannan surveillance may be safely withdrawn from antifungal management of hematology patients on effective antimold prophylaxis: a pilot single-center study. Bone Marrow Transplant 52, 326–329 (2017). https://doi.org/10.1038/bmt.2016.279

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