Haematological Malignancies
Antifungal Treatment in the Blood and Marrow Transplant Setting – Perspectives from Clinical Experience
Report from the 36th Annual Meeting of the European Group for Blood and Marrow Transplantation Held in Vienna, Austria, 21–24 March 2010
Invasive fungal disease (IFD) is a major threat to the success of haematopoietic stem cell transplantation (HSCT), especially in the modern era of reduced-intensity conditioning regimens and wide range of donor sources. Changing fungal epidemiology and mortality rates of 80–90% for certain pathogens1
are adding to the challenge for haematologists and oncologists. Against this background, speakers at the symposium ‘Antifungal treatment in the bone marrow transplant (BMT) setting: Perspectives from clinical experience’, held during the 36th Annual Meeting of the European Group for Blood and Marrow Transplantation in Vienna, Austria on 21–24 March 2010, presented data showing the impact of recent epidemiological and clinical IFD studies on everyday practice in Europe and the US.
Received: 24 May 2010 Accepted: 17 June 2010 Citation: European Oncology, 2010;6(2):53–6 Support: The publication of this article was funded by Schering-Plough.
Who Is At Risk and Why?
Daniel Couriel (The Sarah Cannon Cancer Center, Nashville, TN, US) reviewed recently published data from the Transplant Associated Infection Surveillance Network (TransNet) of 23 US transplant centres, which showed a 12-month cumulative incidence of invasive fungal infection (IFI) among 15,820 HSCT patients of 3.4%.2
Although this is
relatively low, Couriel pointed out that the infection rate in subsets such as allogeneic transplant patients was over six times higher than in those undergoing autologous transplants (8.1% for mismatched related allogeneic versus 1.2% for autologous HSCT).
TransNet data show that invasive aspergillosis (IA) is the biggest threat to HSCT patients. A total of 983 IFIs were identified among 875 HSCT recipients, 43% of which were IA, 28% invasive candidiasis and 8% zygomycosis; other moulds were responsible for 7% of infections and unspecified moulds for a further 6%.2
Couriel explained that further analysis demonstrated the prolonged period during which patients were at risk of some types of IFD. He highlighted the importance of continued awareness and observation, pointing out that, while candidaemia was diagnosed a median 61 days after transplantation, IA was diagnosed a median 99 days, fusarium 123 days and zygomycosis 135 days after transplantation.2
Couriel pointed out that most risk factors for IFD in HSCT patients are host-related, notably neutropenia related to immunosuppression caused by chemotherapy or prolonged steroid treatment and acute or chronic graft-versus-host disease (GvHD) arising from disruption of immune reconstitution.
Changing Definitions
Andrew J Ullmann (Johannes Gutenberg University, Mainz, Germany) reviewed the revised European Organisation for Research and Treatment of Cancer (EORTC)/Mycoses Study Group (MSG) definitions for ‘proven’, ‘probable’ and ‘possible’ IFD published in 2008, which
© TOUCH BRIEFINGS 2010
have expanded the definition of probable disease and reduced the scope of the possible category.3
Probable IFD requires the presence of
a host factor (e.g. recent neutropenia or receipt of allogeneic HSCT), a clinical criterion (e.g. computed tomography [CT] signs of lower respiratory tract fungal infection, evidence of sinonasal or central nervous system [CNS] lesions or disseminated candidiasis) and a mycological criterion (e.g. positive culture or cytology or antigen detection). By contrast, a possible IFD requires only the presence of appropriate host factors and sufficient clinical evidence consistent with IFD (i.e. the presence of pulmonary infiltrates only is insufficient; fungal ‘typical’ infiltrates would be required) but for which there is no mycological support. Proven IFD requires demonstration of fungal elements in diseased tissue, which can include results of indirect assays that are highly specific for the infection being detected.
As Ullmann explained, revised definitions of IFD, variations in the way that treatment success is defined and the adverse effects of host factors, such as low Karnofsky score and the absence of halo sign, all need to be considered when deciding how best to apply clinical trial evidence to everyday practice.
Antifungal Treatment Strategies for Haematopoietic Stem Cell Transplantation Patients
With aspergillosis the most likely fungal challenge for clinicians managing HSCT patients, members of the symposium faculty assessed the effectiveness of the current options for first-line treatment recommended by US and European guidelines – voriconazole or liposomal amphotericin B (L-Amb).4,5
Ullmann compared response and survival data from two key studies of voriconazole and amphotericin B.6,7
In a randomised, unblinded
comparison of intravenous (IV) voriconazole and IV amphotericin B deoxycholate, complete or partial responses at 12 weeks were 53% for voriconazole-treated patients and 32% for amphotericin B-treated
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