title: Fludarabine- and cyclophosphamide-based nonmyeloablative conditioning regimen for transplantation of chronic granulomatous disease: possible correlation with prolonged pure red cell aplasia.
abstract: An 18-year-old patient with chronic granulomatous disease who had had at least 2 episodes of life-threatening Aspergillus pneumonia was treated with nonmyeloablative allogeneic stem cell transplantation (NSCT) from an HLA-identical and major ABO-incompatible sibling. The conditioning regimen consisted of cyclophosphamide at a dose of 60 mg/kg (days -5, -4) and fludarabine at a dose of 30 mg/m2 (days -5, -4, -3, -2, -1). Full donor T-cell engraftment was attained on day 28, and full myeloid engraftment was established by day 150 after tacrolimus withdrawal. The bacteriocidal activity of neutrophils, as indicated by flow cytometry with the use of a dichlorofluorescein diacetate oxidation assay, remained low until 150 days after transplantation, but no infection was detected, a finding that suggests mixed chimerism of granulocytes controlled infection. Graft-versus-host disease and severe regimen-related toxicity (grade 3 or greater) were not observed. This patient developed prolonged pure red cell aplasia, possibly caused by persistent antidonor isohemagglutinin produced by the residual host B-cells. The aplasia resolved with the combination of erythropoietin, double filtration plasmapheresis, and rituximab. In the setting of major ABO-incompatible NSCT, a fludarabine- and cyclophosphamide-based conditioning regimen may lead to prolonged PRCA.
authors.affiliation: Department of Rheumatology and Hematology, Tohoku University School of Medicine, Sendai, Japan.
authors.forename: Tohru
authors.initials: T
authors.lastname: Fujiwara
authors.forename: Minami
authors.initials: M
authors.lastname: Yamada
authors.forename: Koichi
authors.initials: K
authors.lastname: Miyamura
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Tomiya
authors.forename: Kenichi
authors.initials: K
authors.lastname: Ishizawa
authors.forename: Hideo
authors.initials: H
authors.lastname: Harigae
authors.forename: Junichi
authors.initials: J
authors.lastname: Kameoka
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Minegishi
authors.forename: Shigeru
authors.initials: S
authors.lastname: Tsuchiya
authors.forename: Takeshi
authors.initials: T
authors.lastname: Sasaki
mesh_terms: D000017:ABO Blood-Group System; D000293:Adolescent; D001787:Blood Group Incompatibility; D003520:Cyclophosphamide / Q000008:administration & dosage*; D006085:Graft Survival; D006105:Granulomatous Disease, Chronic / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods; D006801:Humans; D008297:Male; D009504:Neutrophils / Q000502:physiology; D012010:Red-Cell Aplasia, Pure / Q000209:etiology / Q000628:therapy; D035781:Siblings; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D014740:Vidarabine / Q000008:administration & dosage* / Q000031:analogs & derivatives*
chemical_list: D000017:ABO Blood-Group System; D003520:Cyclophosphamide; D014740:Vidarabine; C024352:fludarabine