title: Reduced-intensity allogeneic transplantation in pediatric patients ineligible for myeloablative therapy: results of the Pediatric Blood and Marrow Transplant Consortium Study ONC0313.
abstract: The role of reduced-intensity conditioning (RIC) regimens in pediatric cancer treatment is unclear. To define the efficacy of a busulfan/fludarabine/antithymocyte globulin RIC regimen in pediatric patients ineligible for myeloablative transplantation, we completed a trial at 23 institutions in the Pediatric Blood and Marrow Transplant Consortium. Forty-seven patients with hematologic malignancies were enrolled. Sustained engraftment occurred in 98%, 89%, and 90%, and full donor chimerism was achieved in 88%, 76%, and 78% of evaluable related bone marrow/peripheral blood stem cells (BM/PBSCs), unrelated BM/PBSCs, and unrelated cord blood recipients. With a median follow-up of 24 months (range, 11-53 months), 2-year event-free survival, overall survival (OS), transplantation-related mortality, and relapse were 40%, 45%, 11%, and 43%, respectively. Univariate analysis revealed an inferior outcome when patients had undergone previous total body irradiation (TBI)-containing myeloablative transplantation (2-year OS, 23% vs 63% vs 52%, previous TBI transplantation vs no TBI transplantation vs no transplantation, P = .02) and when patients not previously treated with TBI had detectable disease at the time of the RIC procedure (2-year OS, 0% vs 63%, detectable vs nondetectable disease, P = .01). Favorable outcomes can be achieved with RIC approaches in pediatric patients in remission who are ineligible for myeloablative transplantation. This study was registered at www.clinicaltrials.gov as #NCT00795132.
authors.affiliation: Primary Children's Medical Center, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT 84132-2408, USA. michael.pulsipher@hsc.utah.edu
authors.forename: Michael A
authors.initials: MA
authors.lastname: Pulsipher
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Boucher
authors.forename: Donna
authors.initials: D
authors.lastname: Wall
authors.forename: Haydar
authors.initials: H
authors.lastname: Frangoul
authors.forename: Michel
authors.initials: M
authors.lastname: Duval
authors.forename: Rakesh K
authors.initials: RK
authors.lastname: Goyal
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Shaw
authors.forename: Ann E
authors.initials: AE
authors.lastname: Haight
authors.forename: Michael
authors.initials: M
authors.lastname: Grimley
authors.forename: Stephan A
authors.initials: SA
authors.lastname: Grupp
authors.forename: Morris
authors.initials: M
authors.lastname: Kletzel
authors.forename: Richard
authors.initials: R
authors.lastname: Kadota
mesh_terms: D000293:Adolescent; D000328:Adult; D016026:Bone Marrow Transplantation; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D019337:Hematologic Neoplasms / Q000401:mortality / Q000628:therapy*; D006801:Humans; D007223:Infant; D008297:Male; D019653:Myeloablative Agonists / Q000008:administration & dosage; D036102:Peripheral Blood Stem Cell Transplantation; D012008:Recurrence; D015996:Survival Rate; D013997:Time Factors; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous; D014916:Whole-Body Irradiation
chemical_list: D019653:Myeloablative Agonists