Immunology and Host ResponseHematopoietic Stem Cell Transplantation Cures Therapy-refractory Aspergillosis in Chronic Granulomatous DiseaseDedieu, Cinzia MD*,†; Landwehr-Kenzel, Sybille MD*,‡,§; Thee, Stephanie MD, PhD*; Oevermann, Lena MD†; Voigt, Sebastian MD†,¶; Marggraf, Katharina MD*; Schulte, Johannes MD, PhD†; Lau, Susanne MD, PhD*; Roesler, Joachim MD, PhD∥; Kuehl, Jörn-Sven MD†,**; von Bernuth, Horst MD, PhD*,‡,††Author Information From the *Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, Charité Universitätsmedizin †Department of Pediatric Hematology, Oncology and Stem Cell Transplantation ‡Berlin Institute of Health Center for Regenerative Therapies (BCRT), Charité Universitätsmedizin §Berlin Center for Advanced Therapies, Charité - Universitätsmedizin Berlin, Berlin, Germany ¶Department of Infectious Diseases, Robert Koch Institute, Berlin, Germany ∥Department of Pediatrics, Faculty of Medicine Carl Gustav Carus, TU Dresden, Dresden, Germany **Department of Pediatric Oncology, Hematology and Hemostaseology, University of Leipzig, Leipzig, Germany ††Labor Berlin GmbH, Department of Immunology, Berlin, Germany. Accepted for publication February 2, 2021 S.L-.K. was supported by a personal “Clinical Scientist” grant (Charité, BSRT/BCRT) and the Rahel-Hirsch-Habilitation Grant (Charité). H.v.B. has received honoraria from CSL-Behring, Takeda and Swedish Orphan Biovitrum GmbH. The other authors have no conflicts of interest to disclose. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (www.pidj.com). Address for correspondence: Horst von Bernuth, MD, PhD, Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, Charité Berlin - Campus Rudolf Virchow, Augustenburger Platz 1, 13353 Berlin, Germany. E-mail: [email protected]. The Pediatric Infectious Disease Journal: July 2021 - Volume 40 - Issue 7 - p 649-654 doi: 10.1097/INF.0000000000003109 Buy SDC Metrics Abstract Background: Pulmonary invasive aspergillosis is a frequent and life-threatening complication for patients with chronic granulomatous disease (CGD). Despite combined treatment with several groups of antifungal agents, conservative treatment of invasive aspergillosis often remains refractory. Pulmonary invasive aspergillosis is often treated by surgical resection of consolidated lobes or segments, donor granulocyte transfusions and allogeneic hematopoietic stem cell transplantation (HSCT). These options are not mutually exclusive and often combined. Methods and Results: We here describe the treatment of 3 patients with CGD who received HSCT upon active pulmonary invasive aspergillosis: Two of them received HSCT as salvage therapy for refractory aspergillosis, and 1 patient received elective HSCT in infancy but developed pulmonary aspergillosis during secondary graft failure. Based on our experience and available literature, we discuss indication as well as timing of HSCT, granulocyte transfusions and surgery in patients with CGD and pulmonary invasive aspergillosis. Conclusions: Upon diagnosis with invasive aspergillosis in CGD, we propose to start antifungal treatment and preparation for HSCT at the same time. Remission of pulmonary invasive aspergillosis before HSCT remains preferable but is not mandatory. When pulmonary aspergillosis in patients with CGD remains refractory for longer than 3 months on conservative treatment, HSCT without prior surgery or accompanying granulocyte transfusions is a feasible option. Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.