title: Treosulfan-based conditioning for allogeneic HSCT in children with chronic granulomatous disease: a multicenter experience.
abstract: Chronic granulomatous disease (CGD) can be cured by allogeneic hemopoietic stem cell transplantation (HSCT). Complications include graft failure, graft-versus-host disease (GVHD), infection, and transplant-related mortality; therefore, reduced-intensity conditioning regimens are being used to improve outcomes. In this retrospective study, the aim was to determine the outcome of treosulfan-based conditioning in HSCT for pediatric patients with CGD. The following data were collected: risk features pre-HSCT, additional conditioning agents, donor type and stem cell source, toxicity, engraftment, GVHD, chimerism, viral reactivation, post-HSCT complications, length of follow-up, and outcome. Seventy patients (median age, 107 months; interquartile range [IQR], 46-232 months) from 16 centers worldwide were transplanted between 2006 and 2015. Ninety-one percent had high-risk features. Fifty-seven HLA-matched donors, 12 HLA-mismatched donors, and 1 CD3(+)TCR αβ/CD19 depleted parental haploidentical transplants were performed. No major toxicity was reported. Median times to neutrophil and platelet engraftment were 17 (IQR, 15-35) and 16 (IQR, 13-50) days. At a median follow-up of 34 months (IQR, 13-102 months), the overall survival was 91.4%, and event-free survival was 81.4%. The cumulative incidence of acute grade III-IV GVHD was 12%. Nine patients developed chronic GVHD. When split cell chimerism was available, 95% or more myeloid donor chimerism was documented in 80% of surviving patients. Secondary graft failure occurred in 12% of patients. Treosulfan-containing conditioning regimens can be used safely in HSCT for children with CGD and high-risk clinical features, achieving excellent survival with high myeloid chimerism. Further studies are needed to compare with other regimens and evaluate the long-term outcome, particularly on fertility.
authors.affiliation: Department of Paediatric Immunology, Great North Children´s Hospital, Newcastle Upon Tyne, United Kingdom;
authors.forename: Beatriz
authors.initials: B
authors.lastname: Morillo-Gutierrez
authors.affiliation: Hannover Medical School, Hannover, Germany;
authors.forename: Rita
authors.initials: R
authors.lastname: Beier
authors.affiliation: Paediatric Bone Marrow Transplant, Great Ormond Street Hospital, London, United Kingdom;
authors.forename: Kanchan
authors.initials: K
authors.lastname: Rao
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, WA; The University of Washington School of Medicine, Seattle, WA;
authors.forename: Lauri
authors.initials: L
authors.lastname: Burroughs
authors.affiliation: Department of Pediatrics, University Medical Center Ulm, Ulm, Germany;
authors.forename: Ansgar
authors.initials: A
authors.lastname: Schulz
authors.affiliation: Paediatric Bone Marrow Transplantation Schiehallion Unit, Royal Hospital for Sick Children, Glasgow, United Kingdom;
authors.forename: Anna-Maria
authors.initials: AM
authors.lastname: Ewins
authors.affiliation: Paediatric Bone Marrow Transplantation Schiehallion Unit, Royal Hospital for Sick Children, Glasgow, United Kingdom;
authors.forename: Brenda
authors.initials: B
authors.lastname: Gibson
authors.affiliation: Department of Pediatric Hematology and Oncology, Teaching Hospital Motol, Prague, Czech Republic;
authors.forename: Petr
authors.initials: P
authors.lastname: Sedlacek
authors.affiliation: Department of Pediatric Hematology and Oncology, Teaching Hospital Motol, Prague, Czech Republic;
authors.forename: Ladislav
authors.initials: L
authors.lastname: Krol
authors.affiliation: Pediatric Haematology/Oncology, University Medical Centre, Freiburg, Germany;
authors.forename: Brigitte
authors.initials: B
authors.lastname: Strahm
authors.affiliation: Rambam Hospital, Haifa, Israel;
authors.forename: Irina
authors.initials: I
authors.lastname: Zaidman
authors.affiliation: Wroclaw Medical University, Wroclaw, Poland;
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Kalwak
authors.affiliation: Medical College of Wisconsin, Milwaukee, WI;
authors.forename: Julie-An
authors.initials: JA
authors.lastname: Talano
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, WA; The University of Washington School of Medicine, Seattle, WA;
authors.forename: Ann
authors.initials: A
authors.lastname: Woolfrey
authors.affiliation: Lady Cilento Children's Hospital, Brisbane, Australia;
authors.forename: Chris
authors.initials: C
authors.lastname: Fraser
authors.affiliation: Department of Microbiology and Immunology, Department of Pediatrics, University Hospitals Leuven, KU Leuven, Leuven, Belgium;
authors.forename: Isabelle
authors.initials: I
authors.lastname: Meyts
authors.affiliation: University Medical Center Hamburg-Eppendorf, Hamburg, Germany;
authors.forename: Ingo
authors.initials: I
authors.lastname: Müller
authors.affiliation: University of Medical Sciences, Poznan, Poland;
authors.forename: Jacek
authors.initials: J
authors.lastname: Wachowiak
authors.affiliation: San Raffaele Telethon Institute for Gene Therapy, Pediatric Immunohematology and Bone Marrow Transplantation Unit, San Raffaele Scientific Institute, Milan, Italy; and.
authors.forename: Maria Ester
authors.initials: ME
authors.lastname: Bernardo
authors.affiliation: Paediatric Bone Marrow Transplant, Great Ormond Street Hospital, London, United Kingdom;
authors.forename: Paul
authors.initials: P
authors.lastname: Veys
authors.affiliation: Hannover Medical School, Hannover, Germany;
authors.forename: Karl-Walter
authors.initials: KW
authors.lastname: Sykora
authors.affiliation: Department of Paediatric Immunology, Great North Children´s Hospital, Newcastle Upon Tyne, United Kingdom; Institute of Cellular Medicine, Newcastle University, Newcastle Upon Tyne, United Kingdom.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Gennery
authors.affiliation: Department of Paediatric Immunology, Great North Children´s Hospital, Newcastle Upon Tyne, United Kingdom; Institute of Cellular Medicine, Newcastle University, Newcastle Upon Tyne, United Kingdom.
authors.forename: Mary
authors.initials: M
authors.lastname: Slatter
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D064591:Allografts; D001792:Blood Platelets / Q000378:metabolism; D002066:Busulfan / Q000008:administration & dosage / Q000031:analogs & derivatives*; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006085:Graft Survival / Q000187:drug effects; D006086:Graft vs Host Disease / Q000097:blood / Q000401:mortality; D006105:Granulomatous Disease, Chronic / Q000097:blood / Q000401:mortality / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007223:Infant; D008297:Male; D009504:Neutrophils / Q000378:metabolism; D015996:Survival Rate; D019172:Transplantation Conditioning / Q000379:methods*
chemical_list: C018404:treosulfan; D002066:Busulfan