Laura Olivier-Gougenheim1, Nicolas Rama2, Damien Dupont3, Paul Saultier4, Guy Leverger5, Wadih AbouChahla6, Catherine Paillard7, Virginie Gandemer8, Alexandre Theron9, Claire Freycon10, Claire Pluchart11, Pascale Blouin12, Isabelle Pellier13, Sandrine Thouvenin-Doulet14, Claire Desplantes15, Stephane Ducassou16, Caroline Oudot17, Jeremie Rouger-Gaudichon18, Nathalie Cheikh19, Maryline Poiree20, Pascale Schneider21, Genevieve Plat22, Audrey Contet23, Fanny Rialland24, Elodie Gouache5, Benoit Brethon25, Yves Bertrand26, Carine Domenech27. 1. Institute of Pediatric Hematology and Oncology, Hospices Civils de Lyon, University-Lyon1, Lyon, France. Electronic address: olivier_laura@hotmail.fr. 2. Apoptosis, Cancer and Development Laboratory - INSERM U1052-CNRS UMR5286, CRCL, Lyon, France. 3. Institut des Agents Infectieux, Parasitology-Mycology Unit, Lyon, France. 4. CHU Marseille, Pediatric Hematology, -Oncology, Unit, Marseille, France. 5. AP-HP Trousseau, Pediatric Hematology-Oncology Unit, Paris, France. 6. CHU Lille, Pediatric Hematology Unit, Lille, France. 7. CHU Strasbourg, Pediatric Hematology-Oncology Unit, Strasbourg, France. 8. CHU Rennes, Pediatric Hematology, -Oncology, Unit, Rennes, France. 9. CHU Montpellier, Pediatric Hematology-Oncology Unit, Montpellier, France. 10. CHU Grenoble, Pediatric Hematology-Oncology Unit, Grenoble, France. 11. CHU Reims, Pediatric Hematology-Oncology Unit, Institut Jean Godinot, Reims, France. 12. CHU Tours, Pediatric Hematology-Oncology Unit, Tours, France. 13. CHU Angers, Pediatric Hematology-Oncology Unit, Angers, France. 14. CHU St-Etienne, Pediatric Hematology-Oncology Unit, Saint-Etienne, France. 15. CHU Dijon, Pediatric Hematology-Oncology Unit, Dijon, France. 16. CHU Bordeaux, Pediatric Hematology-Oncology Unit, Bordeaux, France. 17. CHU Limoges, Pediatric Hematology-Oncology Unit, Limoges, France. 18. CHU Caen, Pediatric Hematology-Oncology Unit, Caen, France. 19. CHU Besançon, Pediatric Hematology-Oncology Unit, Besançon, France. 20. CHU Lenval Nice, Pediatric Hematology-Oncology Unit, Nice, France. 21. CHU Rouen, Pediatric Hematology-Oncology Unit, Rouen, France. 22. CHU Toulouse, Pediatric Hematology-Oncology Unit, Toulouse, France. 23. CHU Nancy, Pediatric Hematology-Oncology Unit, Nancy, France. 24. CHU Nantes, Pediatric Hematology-Oncology Unit, Nantes, France. 25. AP-HP Robert Debré, Pediatric Hematology Unit, Paris, France. 26. Institute of Pediatric Hematology and Oncology, Hospices Civils de Lyon, University-Lyon1, Lyon, France. 27. Institute of Pediatric Hematology and Oncology, Hospices Civils de Lyon, University-Lyon1, Lyon, France; Apoptosis, Cancer and Development Laboratory - INSERM U1052-CNRS UMR5286, CRCL, Lyon, France.
Abstract
OBJECTIVE: To obtain a national overview of the epidemiology and management of invasive fungal infections (IFIs) in France for severe immunocompromised children who were treated for acute leukemia or had undergone an allogeneic hematopoietic stem cell transplantation (a-HSCT). STUDY DESIGN: We performed a national multicenter retrospective study to collect epidemiologic data for proven and probable IFI in children with acute leukemia under first line or relapse treatment or who had undergone an a-HSCT. We also conducted a prospective practice survey to provide a national overview of IFI management in pediatric hematology units. RESULTS: From January 2014 to December 2017, 144 cases of IFI were diagnosed (5.3%) among 2721 patients: 61 candidiasis, 60 aspergillosis and 23 "emergent" fungi including 10 mucormycosis and 6 fusariosis. Higher IFI rate occurred in patients with acute myeloid leukemia (12.9%), (OR 3.24, 95% CI [2.15-4.81], P < .0001) compared with the entire cohort. Patients undergoing a-HSCT had an IFI rate of only 4.3%. For these patients, the use of primary antifungal prophylaxis, principally fluconazole, was associated with a lower IFI rate (OR 0.28, 95% CI [0.14-0.60], p= 4.90.10-4), compared with a-HSCT patients without prophylaxis. However, receiving prophylaxis children had IFI mostly due to emergent pathogens (41%), such as mucormycosis and fusariosis, which were resistant to prophylactic agent. CONCLUSION: Emerging fungi and new antifungal resistance profiles uncovered in this study should be considered in IFI management in immunocompromised children.
OBJECTIVE: To obtain a national overview of the epidemiology and management of invasive fungal infections (IFIs) in France for severe immunocompromised children who were treated for acute leukemia or had undergone an allogeneic hematopoietic stem cell transplantation (a-HSCT). STUDY DESIGN: We performed a national multicenter retrospective study to collect epidemiologic data for proven and probable IFI in children with acute leukemia under first line or relapse treatment or who had undergone an a-HSCT. We also conducted a prospective practice survey to provide a national overview of IFI management in pediatric hematology units. RESULTS: From January 2014 to December 2017, 144 cases of IFI were diagnosed (5.3%) among 2721 patients: 61 candidiasis, 60 aspergillosis and 23 "emergent" fungi including 10 mucormycosis and 6 fusariosis. Higher IFI rate occurred in patients with acute myeloid leukemia (12.9%), (OR 3.24, 95% CI [2.15-4.81], P < .0001) compared with the entire cohort. Patients undergoing a-HSCT had an IFI rate of only 4.3%. For these patients, the use of primary antifungal prophylaxis, principally fluconazole, was associated with a lower IFI rate (OR 0.28, 95% CI [0.14-0.60], p= 4.90.10-4), compared with a-HSCT patients without prophylaxis. However, receiving prophylaxis children had IFI mostly due to emergent pathogens (41%), such as mucormycosis and fusariosis, which were resistant to prophylactic agent. CONCLUSION: Emerging fungi and new antifungal resistance profiles uncovered in this study should be considered in IFI management in immunocompromised children.