title: Myeloablative intravenous busulfan/fludarabine conditioning does not facilitate reliable engraftment of dual umbilical cord blood grafts in adult recipients.
abstract: The efficacy of once-daily intravenous busulfan with fludarabine as a preparative regimen for partially matched umbilical cord blood transplantation has not been formally studied. We randomized 10 adult patients with myeloid malignancies to receive either concurrent or sequential administration of intravenous busulfan 130 mg/m(2) once daily x 4 days and fludarabine 40 mg/m(2) daily x 4 days, followed by dual umbilical cord blood transplantation. The median combined cryopreserved total nucleated cell dose was 3.6 x 10(7)/kg recipient body weight (range: 2.8-4.5 x 10(7)/kg). Graft-versus-host disease (GVHD) prophylaxis was provided by tacrolimus and mycophenolate mofetil (MMF). Donor-derived neutrophil recovery was observed in only 2 of 10 patients, resulting in premature closure of the study as per graft failure stopping rules. We conclude that the myeloablative conditioning regimen of once-daily intravenous busulfan with fludarabine provides insufficient immunosuppression to allow for engraftment of partially matched, dual umbilical cord blood grafts.
authors.affiliation: Adult Stem Cell Transplant Program, Division of Cellular Therapy, Duke University School of Medicine, Durham, NC 27710, USA. Mitchell.horwitz@duke.edu
authors.forename: Mitchell E
authors.initials: ME
authors.lastname: Horwitz
authors.forename: Ashley
authors.initials: A
authors.lastname: Morris
authors.forename: Cristina
authors.initials: C
authors.lastname: Gasparetto
authors.forename: Keith
authors.initials: K
authors.lastname: Sullivan
authors.forename: Gwynn
authors.initials: G
authors.lastname: Long
authors.forename: John
authors.initials: J
authors.lastname: Chute
authors.forename: David
authors.initials: D
authors.lastname: Rizzieri
authors.forename: Jackie
authors.initials: J
authors.lastname: McPherson
authors.forename: Nelson
authors.initials: N
authors.lastname: Chao
mesh_terms: D000328:Adult; D002066:Busulfan / Q000008:administration & dosage*; D002452:Cell Count; D036101:Cord Blood Stem Cell Transplantation / Q000379:methods* / Q000592:standards; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000517:prevention & control; D006801:Humans; D007951:Leukemia, Myeloid / Q000628:therapy*; D019653:Myeloablative Agonists / Q000627:therapeutic use; D019172:Transplantation Conditioning / Q000379:methods*; D017211:Treatment Failure; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives*
chemical_list: D019653:Myeloablative Agonists; D014740:Vidarabine; D002066:Busulfan; C024352:fludarabine