title: Successful treatment of chronic granulomatous disease with fludarabine-based reduced-intensity conditioning and unrelated bone marrow transplantation.
abstract: Allogeneic hematopoietic stem-cell transplantation (HSCT) for chronic granulomatous disease (CGD) with a reduced-intensity conditioning regimen can be expected to lead to less therapy-related mortality and late-onset impairment, whereas it has also been reported to increase the risk of unsustained mixed donor chimerism and late rejection after transplantation. Herein, we report a 4-year-old boy with CGD who was successfully treated with unrelated bone marrow transplantation with a reduced-intensity conditioning regimen (RIC). Fludarabine-based RIC, 4 Gy of total body irradiation, 120 mg/kg of cyclophosphamide, and 125 mg/m(2) of fludarabine, was adopted for transplantation, followed with 8.9 x 10(8)/kg mononucleated donor cells infused without T-cell depletion. Although hematopoietic engraftment was rapidly obtained by day +17, he developed unstable donor chimerism. After tacrolimus withdrawal, the patient showed grade III acute graft-versus-host disease (GVHD), and subsequently reached full donor chimerism by day +61. Twelve months post-transplant, the patient has remained well with stable and durable engraftment, 100% donor chimerism, and normal superoxide production, without the requirement of donor lymphocyte infusions (DLI).
authors.affiliation: Department of Hematology and Oncology, Kobe Children's Hospital, Suma, Kobe 654-0081, Japan. hasegawa_kch@hp.pref.hyogo.jp
authors.forename: Daiichiro
authors.initials: D
authors.lastname: Hasegawa
authors.forename: Masako
authors.initials: M
authors.lastname: Fukushima
authors.forename: Yuki
authors.initials: Y
authors.lastname: Hosokawa
authors.forename: Hiroki
authors.initials: H
authors.lastname: Takeda
authors.forename: Keiichiro
authors.initials: K
authors.lastname: Kawasaki
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Mizukami
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nunoi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ochiai
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Morio
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Kosaka
mesh_terms: D016026:Bone Marrow Transplantation; D002675:Child, Preschool; D003520:Cyclophosphamide / Q000627:therapeutic use; D006105:Granulomatous Disease, Chronic / Q000628:therapy*; D006801:Humans; D008297:Male; D019653:Myeloablative Agonists / Q000627:therapeutic use; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous; D014740:Vidarabine / Q000031:analogs & derivatives / Q000627:therapeutic use; D014916:Whole-Body Irradiation
chemical_list: D019653:Myeloablative Agonists; D003520:Cyclophosphamide; D014740:Vidarabine; C024352:fludarabine