title: Reduced-intensity conditioning followed by unrelated umbilical cord blood transplantation for advanced hematologic malignancies: rapid engraftment in bone marrow.
abstract: Reduced-intensity (RI) conditioning followed by cord blood transplantation (CBT) is a new treatment modality, but failure to engraft is a major concern. We describe 12 patients with advanced hematologic malignancies who underwent RI conditioning and CBT with a conditioning regimen consisting of 200 mg/m(2) fludarabine (Flu), 50 mg/kg cyclophosphamide (CY), and 3 Gy total body irradiation (TBI). Cyclosporin A and/or methotrexate were used for graft-versus-host disease prophylaxis. Cord blood grafts were not mismatched for more than 2 serologically defined HLA alleles but were later found by high-resolution DNA typing to be mismatched for 2 to 4 alleles in most cases. Short tandem repeat analysis of bone marrow cells at day 14 showed complete donor chimerism in 6 of the patients and mixed chimerism in 5, indicating rapid engraftment in the bone marrow, whereas the remaining patient experienced graft rejection. Neutrophil recovery was achieved at a median of day 17 (range, days 11-24) in 10 of the 11 patients with marrow chimerism at day 14. Of these 10 patients, however, transplantation-related mortality within 100 days occurred in 4 patients who showed failed platelet recovery and a lack of durable engraftment. Overall survival and disease-free survival rates were 41.7% and 33.3%, respectively. These results show that CB mismatched at 2 to 4 HLA alleles and transplanted with the Flu/CY/3 Gy TBI regimen is able to engraft in the bone marrow as early as day 14.
authors.affiliation: Division of Hematology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
authors.forename: Mahito
authors.initials: M
authors.lastname: Misawa
authors.forename: Shunro
authors.initials: S
authors.lastname: Kai
authors.forename: Masaya
authors.initials: M
authors.lastname: Okada
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Nakajima
authors.forename: Kaori
authors.initials: K
authors.lastname: Nomura
authors.forename: Takeshi
authors.initials: T
authors.lastname: Wakae
authors.forename: Akinari
authors.initials: A
authors.lastname: Toda
authors.forename: Hisayuki
authors.initials: H
authors.lastname: Itoi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Takatsuka
authors.forename: Takeyoshi
authors.initials: T
authors.lastname: Itsukuma
authors.forename: Keisuke
authors.initials: K
authors.lastname: Nishioka
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Fujimori
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Ogawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hara
mesh_terms: D000328:Adult; D001853:Bone Marrow; D036101:Cord Blood Stem Cell Transplantation / Q000379:methods / Q000401:mortality; D003520:Cyclophosphamide / Q000008:administration & dosage; D016572:Cyclosporine / Q000008:administration & dosage; D018572:Disease-Free Survival; D005260:Female; D006085:Graft Survival / Q000187:drug effects / Q000528:radiation effects; D006086:Graft vs Host Disease / Q000517:prevention & control; D019337:Hematologic Neoplasms / Q000401:mortality / Q000628:therapy*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D019653:Myeloablative Agonists / Q000008:administration & dosage; D018183:Transplantation Chimera; D019172:Transplantation Conditioning / Q000379:methods / Q000401:mortality; D016896:Treatment Outcome; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives; D014916:Whole-Body Irradiation / Q000379:methods / Q000401:mortality
chemical_list: D007166:Immunosuppressive Agents; D019653:Myeloablative Agonists; D016572:Cyclosporine; D003520:Cyclophosphamide; D014740:Vidarabine; C024352:fludarabine; D008727:Methotrexate