title: Adult dual umbilical cord blood transplantation using myeloablative total body irradiation (1350 cGy) and fludarabine conditioning.
abstract: High treatment-related mortality (TRM) and high graft failure rate are serious concerns in HLA-mismatched umbilical cord blood (UCB) transplantation with myeloablative conditioning. We conducted a prospective trial of dual UCB transplantation using modified myeloablation consisting of total-body irradiation (TBI; 1350 cGy) and fludarabine (Flu) (160 mg/m(2)). Twenty-seven patients (median age, 33 years; range: 20-58 years) with hematologic malignancies were enrolled. The median combined cryopreserved total nucleated cell (TNC) dose was 4.3 × 10(7)/kg (range: 3.2-7.7 × 10(7)/kg). The cumulative incidences of neutrophil (≥500/μL) and platelet (≥50,000/μL) engraftment were 80% (95% confidence interval [CI], 58%-91%) and 68% (95% CI, 46%-83%), respectively. Among engrafted patients, a single cord blood unit was predominant by 100 days posttransplantation. A higher cryopreserved and infused TNC dose and infused CD3(+) cell dose were significant factors associated with the predominant UCB unit (P = .032, .020, and .042, respectively). TRM and relapse rates at 2 years were 28% (95% CI, 12%-47%) and 20% (95% CI, 7%-37%), respectively. Cumulative incidences of grades II-IV and grades III-IV acute graft-versus-host disease (aGVHD) were 37% (95% CI, 20%-55%) and 11% (95% CI, 3%-26%), respectively, and that of chronic GVHD was 31% (95% CI, 15%-49%). With a median follow-up of 23 months, overall survival and disease-free survival rates at 2 years were 58% (95% CI, 34%-75%) and 52% (95% CI, 29%-70%), respectively. This study supports the use of TBI 1350 cGy/Flu as an alternative to conventional myeloablative conditioning for dual UCB transplantation.
authors.affiliation: Adult Stem Cell Transplant Program, Division of Cellular Therapy, Department of Medicine, Duke University Medical Center, Durham, NC 27705, USA. Mitchell.horwitz@duke.edu
authors.forename: Junya
authors.initials: J
authors.lastname: Kanda
authors.forename: David A
authors.initials: DA
authors.lastname: Rizzieri
authors.forename: Cristina
authors.initials: C
authors.lastname: Gasparetto
authors.forename: Gwynn D
authors.initials: GD
authors.lastname: Long
authors.forename: John P
authors.initials: JP
authors.lastname: Chute
authors.forename: Keith M
authors.initials: KM
authors.lastname: Sullivan
authors.forename: Ashley
authors.initials: A
authors.lastname: Morris
authors.forename: Clayton A
authors.initials: CA
authors.lastname: Smith
authors.forename: Donna E
authors.initials: DE
authors.lastname: Hogge
authors.forename: Janet
authors.initials: J
authors.lastname: Nitta
authors.forename: Kevin
authors.initials: K
authors.lastname: Song
authors.forename: Donna
authors.initials: D
authors.lastname: Niedzwiecki
authors.forename: Nelson J
authors.initials: NJ
authors.lastname: Chao
authors.forename: Mitchell E
authors.initials: ME
authors.lastname: Horwitz
mesh_terms: D000328:Adult; D036101:Cord Blood Stem Cell Transplantation / Q000379:methods* / Q000401:mortality; D015925:Cryopreservation; D018572:Disease-Free Survival; D005260:Female; D006084:Graft Rejection / Q000276:immunology / Q000401:mortality / Q000473:pathology* / Q000517:prevention & control*; D006086:Graft vs Host Disease / Q000276:immunology / Q000401:mortality / Q000473:pathology* / Q000628:therapy*; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012008:Recurrence; D019172:Transplantation Conditioning / Q000379:methods*; D016896:Treatment Outcome; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D014916:Whole-Body Irradiation
chemical_list: D006680:HLA Antigens; D014740:Vidarabine; C024352:fludarabine