EClinicalMedicine (Jan 2024)
Influence of invasive aspergillosis during acute leukaemia treatment on survival after allogeneic stem cell transplantation: a prospective study of the EBMT Infectious Diseases Working PartyResearch in context
- Olaf Penack,
- Gloria Tridello,
- Urpu Salmenniemi,
- Rodrigo Martino,
- Nina Khanna,
- Katia Perruccio,
- Franca Fagioli,
- Monika Richert-Przygonska,
- Hélène Labussière-Wallet,
- Johan Maertens,
- Charlotte Jubert,
- Mahmoud Aljurf,
- Herbert Pichler,
- Gergely Kriván,
- Desiree Kunadt,
- Marina Popova,
- Melissa Gabriel,
- Elisabetta Calore,
- Igor Wolfgang Blau,
- Fabio Benedetti,
- Maija Itäla-Remes,
- Elizabeth de Kort,
- Domenico Russo,
- Maura Faraci,
- Anne-Lise Ménard,
- Peter von dem Borne,
- Xavier Poiré,
- Akif Yesilipek,
- Jolanta Gozdzik,
- Zeynep Arzu Yeğin,
- Lucrecia Yañez,
- Luca Facchini,
- Gwendolyn Van Gorkom,
- Lorenz Thurner,
- Ulker Kocak,
- Antònia Sampol,
- Tsila Zuckerman,
- Marc Bierings,
- Stephan Mielke,
- Fabio Ciceri,
- Lotus Wendel,
- Nina Knelange,
- Malgorzata Mikulska,
- Dina Averbuch,
- Jan Styczynski,
- Rafael de la Camara,
- Simone Cesaro
Affiliations
- Olaf Penack
- Medizinische Klinik m. S. Hämatologie, Onkologie und Tumorimmunologie, Berlin, Germany; Corresponding author. Department for Hematology, Oncology and Tumorimmunology, Charité Universitätsmedizin Berlin, Campus Virchow Clinic, Augustenburger Platz 1, 13353, Berlin, Germany.
- Gloria Tridello
- EBMT Leiden Study Unit, Leiden, the Netherlands
- Urpu Salmenniemi
- HUCH Comprehensive Cancer Center, Helsinki, Finland
- Rodrigo Martino
- Hospital Santa Creu i Sant Pau, Barcelona, Spain
- Nina Khanna
- Division of Infectious Diseases, University Hospital, Basel, Switzerland
- Katia Perruccio
- Pediatric Oncology Hematology and Stem Cell Transplantation Program, Santa Maria Della Misericordia Hospital, Perugia
- Franca Fagioli
- Ospedale Infantile Regina Margherita, Torino, Italy
- Monika Richert-Przygonska
- Department of Pediatric Hematology and Oncology, Collegium Medicum, Nicolaus Copernicus University Torun, Bydgoszcz, Poland
- Hélène Labussière-Wallet
- Hopital Lyon Sud, Hospices Civils de Lyon, Pierre Bénite, France
- Johan Maertens
- University Hospital Gasthuisberg, Leuven, Belgium
- Charlotte Jubert
- CHU Bordeaux Groupe Hospitalier Pellegrin-Enfants, Bordeaux, France
- Mahmoud Aljurf
- King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia
- Herbert Pichler
- Department of Pediatrics and Adolescent Medicine, St. Anna Children's Hospital, Medical University of Vienna, Vienna, Austria
- Gergely Kriván
- Central Hospital of Southern Pest, Budapest, Hungary
- Desiree Kunadt
- University Hospital, TU Dresden, Germany
- Marina Popova
- RM Gorbacheva Research Institute, Pavlov University, St. Petersburg, Russian Federation
- Melissa Gabriel
- Cancer Centre for Children, The Children's Hospital at Westmead, Sydney, Australia
- Elisabetta Calore
- Pediatric Hematology Oncology and Stem Cell Transplant Division, Department of Women's and Children's Health, Azienda Ospedale-UniversitàPadova, Italy
- Igor Wolfgang Blau
- Medizinische Klinik m. S. Hämatologie, Onkologie und Tumorimmunologie, Berlin, Germany
- Fabio Benedetti
- Policlinico G.B. Rossi, Verona, Italy
- Maija Itäla-Remes
- Turku University Hospital, Turku, Finland
- Elizabeth de Kort
- Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands
- Domenico Russo
- Unit of Blood Diseases and Bone Marrow Transplantation, Brescia University, Italy
- Maura Faraci
- HSCT Unit, Department of Hematology-Oncology, IRCCS Istituto G. Gaslini, Genova, Italy
- Anne-Lise Ménard
- Centre Henri Becquerel, Rouen, France
- Peter von dem Borne
- Leiden University Hospital, Leiden, the Netherlands
- Xavier Poiré
- Cliniques Universitaires St. Luc, Brussels, Belgium
- Akif Yesilipek
- Medical Park Antalya Hospital, Antalya, Turkey
- Jolanta Gozdzik
- Department of Clinical Immunology and Transplantation, Jagiellonian University Medical Collage, University Children's Hospital in Krakow, Poland
- Zeynep Arzu Yeğin
- Gazi University Faculty of Medicine, Ankara, Turkey
- Lucrecia Yañez
- Hospital U. Marqués de Valdecilla-IDIVAL, Santander, Spain
- Luca Facchini
- Hematology, AUSL-IRCCS Reggio Emilia, Italy
- Gwendolyn Van Gorkom
- University Hospital Maastricht, Maastricht, the Netherlands
- Lorenz Thurner
- Lorenz Thurner, University of Saarland, Homburg, Germany
- Ulker Kocak
- Gazi University School of Medicine, Ankara, Turkey
- Antònia Sampol
- Hospital Son Espases, Palma de Mallorca, Balearic Islands, Spain
- Tsila Zuckerman
- Rambam Medical Center, Technion –Faculty of Medicine. Haifa, Israel
- Marc Bierings
- Princess Maxima Center/ University Hospital for Children (WKZ), Utrecht, the Netherlands
- Stephan Mielke
- Karolinska University Hospital, Stockholm, Sweden
- Fabio Ciceri
- Università Vita Salute San Raffaele, Milan, Italy
- Lotus Wendel
- EBMT Leiden Study Unit, Leiden, the Netherlands
- Nina Knelange
- EBMT Leiden Study Unit, Leiden, the Netherlands
- Malgorzata Mikulska
- Division of Infectious Diseases, University of Genoa and Ospedale Policlinico San Martino, Genoa, Italy
- Dina Averbuch
- Pediatric Infectious Diseases, Faculty of Medicine, Hebrew University of Jerusalem, Hadassah Medical Center, Israel
- Jan Styczynski
- Department of Pediatric Hematology and Oncology, Collegium Medicum, Nicolaus Copernicus University Torun, Bydgoszcz, Poland
- Rafael de la Camara
- Rafael de la Camara, Hospital de la Princesa, Madrid, Spain
- Simone Cesaro
- Pediatric Hematology Oncology, Department of Mother and Child, Azienda Ospedaliera Universitaria Integrata, Verona, Italy
- Journal volume & issue
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Vol. 67
p. 102393
Abstract
Summary: Background: Infections are the main reason for mortality during acute leukaemia treatment and invasive aspergillosis (IA) is a major concern. Allogeneic stem cell transplantation (alloSCT) is a standard therapy and often is the only live-saving procedure in leukaemia patients. The profound immunodeficiency occurring after alloSCT led to high IA-associated mortality in the past. Therefore, patients with IA were historically considered transplant-ineligible. Recently, there has been improvement of anti-fungal management including novel anti-fungal agents. As a result, more leukaemia patients with IA are undergoing alloSCT. Outcome has not been prospectively assessed. Methods: We performed a prospective study in acute leukaemia patients undergoing alloSCT to analyse the impact of a prior history of probable or proven IA (pre-SCT IA). The primary endpoint was 1-year non-relapse mortality (NRM). Relapse free survival and overall survival were analysed as secondary endpoints. Findings: 1439 patients were included between 2016 and 2021. The incidence of probable or proven pre-SCT IA was 6.0% (n = 87). The cumulative incidence of 1-year NRM was 17.3% (95% CI 10.2–26.0) and 11.2% (9.6–13.0) for patients with and without pre-SCT IA. In multivariate analyses the hazard ratio (HR) for 1-year NRM was 2.1 (1.2–3.6; p = 0.009) for patients with pre-SCT IA. One-year relapse-free survival was inferior in patients with pre-SCT IA (59.4% [48.3–68.9] vs. 70.4 [67.9–72.8]; multivariate HR 1.5 [1.1–2.1]; p = 0.02). Consequently, 1-year overall survival was lower in patients with pre-SCT IA: (68.8% [57.8–77.4] vs. 79.0% [76.7–81.1]; multivariate HR 1.7 [1.1–2.5]; p = 0.01). Interpretation: Pre-SCT IA remains to be significantly associated with impaired alloSCT outcome. On the other hand, more than two thirds of patients with pre-SCT IA were alive at one year after alloSCT. IA is not anymore an absolute contraindication for alloSCT because the majority of patients with IA who undergo alloSCT benefit from this procedure. Funding: There was no external funding source for this study.
