Management of Invasive Fungal Infections in Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation: The Turin Experience
Alessandro Busca,Natascia Cinatti,Jessica Gill,Roberto Passera,Chiara Dellacasa,Luisa Giaccone,Irene Dogliotti,Sara Manetta,Silvia Corcione,Francesco Giuseppe De Rosa +9 more
TLDR
The presence of IFI had a significant impact on overall survival at 1 year (IFI, 32.8%) and mortality rate was 20.7% in the overall population, 17% in patients with probable IFI, and 36% in Patients with proven IFI.Abstract:
Background Allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients are exposed to an increased risk of invasive fungal infections (IFIs) due to neutropenia, immunosuppressive treatments, graft-versus-host disease (GvHD) and incomplete immune reconstitution. Although clinical benefit from antifungal prophylaxis has been demonstrated, IFIs remain a leading cause of morbidity and mortality in these patients. In the last decades, attention has also been focused on potential risk factors for IFI to tailor an antifungal prevention strategy based on risk stratification. Aim of the Study This retrospective single-center study aimed to assess the epidemiology and the prognostic factors of IFI in a large cohort of allo-HSCT patients. Methods Between January 2004 and December 2020, 563 patients with hematological malignancies received an allo-HSCT at the Stem Cell Transplant Unit in Turin: 191 patients (34%) received grafts from a matched sibling donor, 284 (50.5%) from a matched unrelated donor, and 87 (15.5%) from an haploidentical family member. The graft source was peripheral blood in 81.5% of the patients. Our policy for antifungal prophylaxis included fluconazole in matched related and unrelated donors, while micafungin was administered in patients receiving haploidentical transplant. According to this practice, fluconazole was administered in 441 patients (79.6%) and micafungin in 62 (11.2%), while only 9 patients received mold-active prophylaxis. Galactomannan testing was routinely performed twice a week; patients with persisting fever unresponsive to broad spectrum antibiotics were evaluated with lung high-resolution computed tomography (HRCT) scan. In case of imaging suggestive of IFI, bronchoalveolar lavage (BAL) was performed whenever feasible. Statistical Analysis Only probable/proven IFI (PP-IFI) occurring during the first 12 months after transplant have been evaluated. IFIs were classified as probable or proven according to the new revised European Organization for Research and Treatment of Cancer (EORTC)/Mycoses Study Group (MSG) consensus criteria. Multivariate competing risk regression, binary logistic, and proportional hazard models were performed to identify risk factors for PP-IFI. Results A total of 58 PP-IFIs (n = 47 probable; n = 11 proven) occurred in our patients resulting in a cumulative incidence of 4.1%, 8.1%, and 9.6% at 30, 180, and 365 days, respectively. Molds were the predominant agents (n = 50 Aspergillus; n = 1 Mucor), followed by invasive candidemia (n = 5 non-albicans Candida; n = 1 Candida albicans; n = 1 Trichosporon). Lung was the most frequent site involved in patients with mold infections (47/51, 92.2%). Median time from HSCT to IFI was 98.44 days (0–365 days). Only 34.5% of patients with IFI were neutropenic at the time of infection. The presence of IFI had a significant impact on overall survival at 1 year (IFI, 32.8% vs. non-IFI, 54.6%; p < 0.001). IFI-related mortality rate was 20.7% in the overall population, 17% in patients with probable IFI, and 36% in patients with proven IFI. Multivariate competing risk regression revealed that donor type was the factor significantly associated to the risk of IFI [subdistribution hazard ratio (SDHR), 1.91, IC 1.13–3.20; p = 0.015]. BAL was informative in a consistent number of cases (36/57, 63.2%) leading to the identification of fungal (21), bacterial (4), viral (3), and polymicrobial (8) infections. Overall, 79 patients (14%) received a diagnostic-driven treatment, and 63 patients (11.2%) received a fever-driven treatment. Liposomal amphoteric B was the drug used in the majority of patients receiving diagnostic-driven therapy (30/79, 38%), while caspofungin was administered more frequently in patients who received a fever-driven strategy (27/63, 42.9%). Conclusion According to our experience, a non-mold active prophylaxis in patients undergoing allo-HSCT is feasible when combined with an intensive diagnostic work-up including CT scan and BAL. BAL performed at the onset of the disease may provide informative results in most patients. A diagnostic-driven treatment strategy may contribute to limit the use of costly antifungal therapies.read more
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Bacterial Bloodstream Infections after Allogeneic Hematopoietic Stem Cell Transplantation: Etiology, Risk Factors and Outcome in a Single-Center Study
Jessica Gill,Alessandro Busca,Natascia Cinatti,Roberto Passera,Chiara Dellacasa,Luisa Giaccone,Irene Dogliotti,Sara Manetta,Silvia Corcione,Francesco Giuseppe De Rosa +9 more
TL;DR: In this paper , the authors performed an observational, retrospective, single-center study on patients undergoing allogeneic hematopoietic stem cell transplant (allo-HSCT) between 2004 and 2020 at the Stem Cell Transplant Unit in Turin to assess the incidence, etiology, and outcomes of bacterial bloodstream infections (BSIs) and explore any risk factors for bacteriaemia.
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External evaluation of published population pharmacokinetic models of posaconazole
Shuqi Huang,Qin Ding,Nan-ping Yang,Zexu Sun,Qian Cheng,Wei Li,Yejun Li,Xin Chen,Cuifang Wu,Qi Pei +9 more
TL;DR: Bayesian forecasting significantly improved the predictive per-formance of the models with two or three prior observations, and the applicability of these published posaconazole PopPK models extrapolated to the authors' center was unsatisfactory.
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Invasive mycoses in patients with hematological malignancies and recipients of hematopoietic stem cell transplantation: results of a systematic review, literature review and meta-analysis
M. Popova,Yu. A. Rogacheva +1 more
TL;DR: In this paper , the authors conducted a systematic review with a meta-analysis of data on the IM etiological structure in patients of all ages receiving therapy for oncohematological diseases, including patients who underwent hematopoietic stem cell transplantation.
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National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: I. Diagnosis and Staging Working Group Report
Madan Jagasia,Hildegard T. Greinix,Mukta Arora,Kirsten M. Williams,Daniel Wolff,Edward W. Cowen,Jeanne Palmer,Daniel J. Weisdorf,Nathaniel S. Treister,Guang-Shing Cheng,Holly Kerr,Pamela Stratton,Rafael F. Duarte,George B. McDonald,Yoshihiro Inamoto,Afonso Celso Vigorito,Sally Arai,Manuel B. Datiles,David A. Jacobsohn,Theo Heller,Carrie L. Kitko,Sandra A. Mitchell,Paul J. Martin,Howard M. Shulman,Roy S. Wu,Corey Cutler,Georgia B. Vogelsang,Stephanie J. Lee,Steven Z. Pavletic,Mary E.D. Flowers +29 more
TL;DR: The 2014 NIH consensus maintains the framework of the prior consensus with further refinement based on new evidence, and focuses attention on the causes of organ-specific abnormalities to chronic GVHD.
Journal ArticleDOI
National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease
Madan Jagasia,Hildegard T. Greinix,Mukta Arora,Kirsten M. Williams,Daniel Wolff,Edward W. Cowen,Jeanne Palmer,Daniel J. Weisdorf,Nathaniel S. Treister,Guang-Shing Cheng,Holly Kerr,Pamela Stratton,Rafael F. Duarte,George B. McDonald,Yoshihiro Inamoto,Afonso Celso Vigorito,Sally Arai,Manuel B. Datiles,David A. Jacobsohn,Theo Heller,Carrie L. Kitko,Sandra A. Mitchell,Paul J. Martin,Howard M. Shulman,Roy S. Wu,Corey Cutler,Georgia B. Vogelsang,Stephanie J. Lee,Steven Z. Pavletic,Mary E.D. Flowers +29 more
TL;DR: In this article, the authors proposed a new clinical scoring system (0-3) that describes the extent and severity of chronic graft-versus-host disease for each organ or site at any given time, taking functional impact into account.
Journal ArticleDOI
Hematopoietic cell transplantation (HCT)-specific comorbidity index: a new tool for risk assessment before allogeneic HCT.
Mohamed L. Sorror,Michael B. Maris,Michael B. Maris,Rainer Storb,Rainer Storb,Frédéric Baron,Brenda M. Sandmaier,Brenda M. Sandmaier,David G. Maloney,David G. Maloney,Barry E. Storer,Barry E. Storer +11 more
TL;DR: The new simple index provided valid and reliable scoring of pretransplant comorbidities that predicted nonrelapse mortality and survival and will be useful for clinical trials and patient counseling before HCT.
Journal ArticleDOI
Prospective Surveillance for Invasive Fungal Infections in Hematopoietic Stem Cell Transplant Recipients, 2001–2006: Overview of the Transplant-Associated Infection Surveillance Network (TRANSNET) Database
Dimitrios P. Kontoyiennis,Kieren A. Marr,Benjamin J. Park,Barbara D. Alexander,Elias Anaissie,Thomas J. Walsh,James I. Ito,David R. Andes,John W. Baddley,Janice M. Brown,Lisa Brumble,Alison G. Freifeld,Susan Hadley,Loreen A. Herwaldt,Carol A. Kauffman,Katherine M. Knapp,G. Marshall Lyon,Vicki A. Morrison,Genovefa A. Papanicolaou,Thomas F. Patterson,Trish M. Perl,Mindy G. Schuster,Randall C. Walker,Kathleen A. Wannemuehler,John R. Wingard,Tom M. Chiller,Peter G. Pappas +26 more
TL;DR: In this national prospective surveillance study of IFIs in HSCT recipients, the cumulative incidence was highest for aspergillosis, followed by candidiasis, and understanding the epidemiologic trends and burden of IFI may lead to improved management strategies and study design.
Journal ArticleDOI
Revision and Update of the Consensus Definitions of Invasive Fungal Disease From the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium
J. Peter Donnelly,Sharon C.-A. Chen,Carol A. Kauffman,William J. Steinbach,John W. Baddley,Paul E. Verweij,Cornelius J. Clancy,John R. Wingard,Shawn R. Lockhart,Andreas H. Groll,Tania C. Sorrell,Matteo Bassetti,Hamdi Akan,Barbara D. Alexander,David R. Andes,Elie Azoulay,Ralf Bialek,Robert W. Bradsher,Stéphane Bretagne,Thierry Calandra,Angela M. Caliendo,Elio Castagnola,Mario Cruciani,Manuel Cuenca-Estrella,Catherine F. Decker,Sujal R. Desai,Brian T. Fisher,Thomas S. Harrison,Claus Peter Heussel,Henrik Jeldtoft Jensen,Christopher C. Kibbler,Dimitrios P. Kontoyiannis,Bart Jan Kullberg,Katrien Lagrou,Frédéric Lamoth,Thomas Lehrnbecher,J. Loeffler,Olivier Lortholary,Johan Maertens,O. Marchetti,Kieren A. Marr,Henry Masur,Jacques F. Meis,C. Orla Morrisey,Marcio Nucci,Luis Ostrosky-Zeichner,Livio Pagano,Thomas F. Patterson,John R. Perfect,Zdenek Racil,Emmanuel Roilides,Marcus Ruhnke,Cornelia Schaefer Prokop,Shmuel Shoham,Monica A. Slavin,David A. Stevens,George Richard Thompson,Jose A. Vazquez,Claudio Viscoli,Thomas J. Walsh,Adilia Warris,L. Joseph Wheat,P. Lewis White,Theoklis E. Zaoutis,Peter G. Pappas +64 more
TL;DR: These updated definitions of IFDs should prove applicable in clinical, diagnostic, and epidemiologic research of a broader range of patients at high-risk.