title: Double unrelated reduced-intensity umbilical cord blood transplantation in adults.
abstract: Umbilical cord blood (UBC) stem cells are a useful stem cell source for patients without matched related or unrelated donors. Adult transplantation with single UBC units is associated with high transplantation-related mortality (TRM). In most cases, mortality is due to infection related to slow engraftment and immunoincompetence. In this study, we used a reduced-intensity conditioning regimen of fludarabine, melphalan, and antithymocyte globulin followed by 2 partially matched UBC units. The UBC units were a 4/6 HLA match or better with each other and with the patient and achieved a minimum precryopreservation cell dose of 3.7 x 10(7) nucleated cells/kg. A total of 21 patients (median age, 49 years) were treated. The median time to an absolute neutrophil count > 0.5 x 10(9)/L was 20 days, and the median time to an unsupported platelet count > 20 x 10(9)/L was 41 days. Two patients experienced primary graft failure and underwent a second UBC transplantation. One patient had a late graft failure. Acute graft-versus-host disease (GVHD) grade II-IV occurred in 40% of patients. The 100-day TRM was 14%, and the 1-year disease-free survival was 67%. Mixed chimerism was associated with a higher risk of chronic GVHD. Our findings indicate that adult patients can tolerate double UBC transplantation well and achieve sustained antitumor responses using this reduced-intensity conditioning regimen.
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114, USA. kballen@partners.org
authors.forename: Karen K
authors.initials: KK
authors.lastname: Ballen
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Spitzer
authors.forename: Beow Y
authors.initials: BY
authors.lastname: Yeap
authors.forename: Steven
authors.initials: S
authors.lastname: McAfee
authors.forename: Bimalangshu R
authors.initials: BR
authors.lastname: Dey
authors.forename: Eyal
authors.initials: E
authors.lastname: Attar
authors.forename: Richard
authors.initials: R
authors.lastname: Haspel
authors.forename: Grace
authors.initials: G
authors.lastname: Kao
authors.forename: Deborah
authors.initials: D
authors.lastname: Liney
authors.forename: Edwin
authors.initials: E
authors.lastname: Alyea
authors.forename: Stephanie
authors.initials: S
authors.lastname: Lee
authors.forename: Corey
authors.initials: C
authors.lastname: Cutler
authors.forename: Vincent
authors.initials: V
authors.lastname: Ho
authors.forename: Robert
authors.initials: R
authors.lastname: Soiffer
authors.forename: Joseph H
authors.initials: JH
authors.lastname: Antin
mesh_terms: D000328:Adult; D000961:Antilymphocyte Serum / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D036101:Cord Blood Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D005260:Female; D006085:Graft Survival; D006086:Graft vs Host Disease; D006650:Histocompatibility Testing; D006801:Humans; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D008875:Middle Aged; D016019:Survival Analysis; D018183:Transplantation Chimera / Q000276:immunology*; D019172:Transplantation Conditioning / Q000379:methods*; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives
chemical_list: D000961:Antilymphocyte Serum; D014740:Vidarabine; C024352:fludarabine; D008558:Melphalan