Mainly Post-Transplant Factors Are Associated with Invasive Aspergillosis after Allogeneic Stem Cell Transplantation: A Study from the Surveillance des Aspergilloses Invasives en France and Société Francophone de Greffe de Moelle et de Thérapie Cellulaire

• Published in: Biology of blood and marrow transplantation Vol. 25; no. 2; pp. 354 - 361
• Main Authors: Robin, Christine, Cordonnier, Catherine, Sitbon, Karine, Raus, Nicole, Lortholary, Olivier, Maury, Sébastien, Peffault de la Tour, Regis, Bretagne, Stéphane, Bastuji-Garin, Sylvie
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.02.2019; Elsevier
• Subjects: Acute Disease; Adult; Allogeneic stem cell transplantation; Allografts; Aspergillosis; Aspergillosis - epidemiology; Aspergillosis - etiology; Europe; Female; Graft vs Host Disease - epidemiology; Graft vs Host Disease - etiology; Graft vs Host Disease - microbiology; Hematopoietic Stem Cell Transplantation; Humans; Invasive fungal infection; Life Sciences; Male; Microbiology and Parasitology; Middle Aged; Mycology; Neutropenia - epidemiology; Neutropenia - etiology; Neutropenia - microbiology; Prospective Studies; Recurrence; Registries; Retrospective Studies; Risk Factors; Societies, Medical; Europe; Allogeneic stem cell transplantation; Invasive fungal infection; Aspergillosis
• ISSN: 1083-8791; 1523-6536; 1523-6536
• DOI: 10.1016/j.bbmt.2018.09.028

•This was the largest series of invasive aspergillosis in allogeneic HCT patients in Europe.•Most cases (63%) were observed after day 100, making IA a late complication of HCT.•The risk of IA was associated with post-transplant factors whatever the date of onset.•IA occurrence cannot be reliably predicted before transplant.•GVHD, secondary neutropenia, and relapse remain associated with IA in the RIC era. Invasive aspergillosis (IA) occurs in up to 23% of allogeneic hematopoietic stem cell transplantation (HSCT) patients. Although transplant procedures have changed over time, more late cases of IA are being observed. The objective of this study was to identify the pre- and post-transplant factors of IA in a large cohort of HSCT patients mainly transplanted with reduced-intensity conditioning. This multicenter, case-control study was carried out using data collected between 2005 and 2010 by the Surveillance des Aspergilloses Invasives en France program (Institut Pasteur, Paris) and the European Society for Blood and Marrow Transplantation ProMISe registry. Four control subjects without IA were individually matched to each case based on the center, patient age, and year of the transplant. We identified 185 cases of probable and proven IA and 651 control subjects. The median date of IA after the transplant was 133 days, with 35 cases (19%) of early IA (before day 40), 33 cases (18%) of late IA (days 40 to 100), and 117 cases (63%) cases of very late IA (after day 100). In the multivariate analysis early IA was significantly associated with a lack of engraftment, whereas late and very late IA were significantly associated with more than grade II acute graft-versus-host disease (GVHD); very late IA was also significantly associated with relapse and secondary neutropenia. Two-thirds of IA cases occurred more than 100 days after HSCT with different risk factors from those occurring earlier. Prophylactic strategies should consider the specific risk factors for late and very late IA, especially GVHD, relapse after transplant, and secondary neutropenia.