title: Alternative donor transplantation after reduced intensity conditioning: results of parallel phase 2 trials using partially HLA-mismatched related bone marrow or unrelated double umbilical cord blood grafts.
abstract: The Blood and Marrow Transplant Clinical Trials Network conducted 2 parallel multicenter phase 2 trials for individuals with leukemia or lymphoma and no suitable related donor. Reduced intensity conditioning (RIC) was used with either unrelated double umbilical cord blood (dUCB) or HLA-haploidentical related donor bone marrow (Haplo-marrow) transplantation. For both trials, the transplantation conditioning regimen incorporated cyclophosphamide, fludarabine, and 200 cGy of total body irradiation. The 1-year probabilities of overall and progression-free survival were 54% and 46%, respectively, after dUCB transplantation (n = 50) and 62% and 48%, respectively, after Haplo-marrow transplantation (n = 50). The day +56 cumulative incidence of neutrophil recovery was 94% after dUCB and 96% after Haplo-marrow transplantation. The 100-day cumulative incidence of grade II-IV acute GVHD was 40% after dUCB and 32% after Haplo-marrow transplantation. The 1-year cumulative incidences of nonrelapse mortality and relapse after dUCB transplantation were 24% and 31%, respectively, with corresponding results of 7% and 45%, respectively, after Haplo-marrow transplantation. These multicenter studies confirm the utility of dUCB and Haplo-marrow as alternative donor sources and set the stage for a multicenter randomized clinical trial to assess the relative efficacy of these 2 strategies. The trials are registered at www.clinicaltrials.gov under NCT00864227 (BMT CTN 0604) and NCT00849147 (BMT CTN 0603).
authors.affiliation: Blood and Marrow Transplant Program, University of Minnesota, Minneapolis, MN, USA. bruns072@umn.edu
authors.forename: Claudio G
authors.initials: CG
authors.lastname: Brunstein
authors.forename: Ephraim J
authors.initials: EJ
authors.lastname: Fuchs
authors.forename: Shelly L
authors.initials: SL
authors.lastname: Carter
authors.forename: Chatchada
authors.initials: C
authors.lastname: Karanes
authors.forename: Luciano J
authors.initials: LJ
authors.lastname: Costa
authors.forename: Juan
authors.initials: J
authors.lastname: Wu
authors.forename: Steven M
authors.initials: SM
authors.lastname: Devine
authors.forename: John R
authors.initials: JR
authors.lastname: Wingard
authors.forename: Omar S
authors.initials: OS
authors.lastname: Aljitawi
authors.forename: Corey S
authors.initials: CS
authors.lastname: Cutler
authors.forename: Madan H
authors.initials: MH
authors.lastname: Jagasia
authors.forename: Karen K
authors.initials: KK
authors.lastname: Ballen
authors.forename: Mary
authors.initials: M
authors.lastname: Eapen
authors.forename: Paul V
authors.initials: PV
authors.lastname: O'Donnell
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000465:Algorithms; D016026:Bone Marrow Transplantation / Q000276:immunology / Q000379:methods*; D002648:Child; D005190:Family; D005260:Female; D005312:Fetal Blood / Q000276:immunology / Q000637:transplantation*; D006085:Graft Survival; D006680:HLA Antigens / Q000032:analysis / Q000276:immunology*; D019337:Hematologic Neoplasms / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006650:Histocompatibility Testing / Q000379:methods; D006801:Humans; D008297:Male; D008875:Middle Aged; D016019:Survival Analysis; D014019:Tissue Donors; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous; D055815:Young Adult
chemical_list: D006680:HLA Antigens