title: The development of a myeloablative, reduced-toxicity, conditioning regimen for cord blood transplantation.
abstract: Cord blood transplantation is being used with increasing frequency for patients with high-risk hematologic malignancies. Myeloablative preparative regimens provide antitumor efficacy and facilitate engraftment but are associated with higher morbidity and nonrelapse mortality rates than nonablative regimens. We evaluated 3 sequential myeloablative regimens in the cord blood transplant setting. Regimen 1 (melphalan, fludarabine, and thiotepa) produced prompt engraftment and minimal engraftment failure but was associated with a high nonrelapse mortality rate. Regimen 2 (busulfan and fludarabine) was very well tolerated but was associated with a high rate of engraftment failure and relapse. Regimen 3 (busulfan, clofarabine, fludarabine, and low-dose total body irradiation given 9 days after the chemotherapy) was associated with a low rate of engraftment failure but was logistically difficult to administer. Finally, regimen 3 that included the total body irradiation given immediately after the chemotherapy was well tolerated, with prompt engraftment and tumor control. This latter regimen appears to be effective in preliminary studies and warrants further evaluation.
authors.affiliation: Division of Hematology-Oncology, University of Pittsburgh Medical Center, Pittsburgh, PA. Electronic address: mehtars@upmc.edu.
authors.forename: Rohtesh S
authors.initials: RS
authors.lastname: Mehta
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Antonio
authors.initials: A
authors.lastname: Di Stasi
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Borje S
authors.initials: BS
authors.lastname: Andersson
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Yago
authors.initials: Y
authors.lastname: Nieto
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Roy
authors.initials: R
authors.lastname: Jones
authors.affiliation: Case Western University, Cleveland, OH.
authors.forename: Marcos
authors.initials: M
authors.lastname: de Lima
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Chitra
authors.initials: C
authors.lastname: Hosing
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Uday
authors.initials: U
authors.lastname: Popat
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Partow
authors.initials: P
authors.lastname: Kebriaei
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Betul
authors.initials: B
authors.lastname: Oran
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Amin
authors.initials: A
authors.lastname: Alousi
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Katayoun
authors.initials: K
authors.lastname: Rezvani
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Muzaffar
authors.initials: M
authors.lastname: Qazilbash
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Qaiser
authors.initials: Q
authors.lastname: Bashir
authors.affiliation: Center for Cell & Gene Therapy, Houston, TX.
authors.forename: Catherine
authors.initials: C
authors.lastname: Bollard
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Laurence
authors.initials: L
authors.lastname: Cooper
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Laura
authors.initials: L
authors.lastname: Worth
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Priti
authors.initials: P
authors.lastname: Tewari
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Ian
authors.initials: I
authors.lastname: McNiece
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Kaci
authors.initials: K
authors.lastname: Willhelm
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Richard
authors.initials: R
authors.lastname: Champlin
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Shpall
mesh_terms: D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D036101:Cord Blood Stem Cell Transplantation / Q000379:methods*; D005312:Fetal Blood / Q000637:transplantation*; D042381:Granulocyte Precursor Cells / Q000187:drug effects*; D019337:Hematologic Neoplasms / Q000188:drug therapy* / Q000628:therapy*; D006801:Humans; D007223:Infant; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000517:prevention & control; D014916:Whole-Body Irradiation / Q000379:methods; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents
keywords: Conditioning regimen; Hematologic malignancies; Stem cell transplant; Total body irradiation; Treatment related mortality