title: Combination of linear accelerator-based intensity-modulated total marrow irradiation and myeloablative fludarabine/busulfan: a phase I study.
abstract: Here we examined the addition of intensity-modulated total marrow irradiation (TMI) delivered using a linear accelerator to a myeloablative chemotherapy conditioning regimen before allogeneic hematopoietic stem cell transplantation (HSCT). In this phase I study, we enrolled 14 patients with high-risk hematologic malignancies who received escalating doses of TMI at 3 Gy (n = 3), 6 Gy (n = 3), 9 Gy (n = 6), and 12 Gy (n = 2) in combination with intravenous (i.v.) fludarabine 160 mg/m(2) and targeted busulfan (area under the curve, 4800 μM*minute). Peripheral blood mobilized stem cells were obtained from HLA-matched related (n = 9) or unrelated (n = 4) or 1 antigen-mismatched unrelated (n = 1) donors. All patients rapidly engrafted and recovered their immune cells. Overall, Bearman extrahematologic toxicity were limited to grades 1 or 2, with oral mucositis grade 1 in 64% and grade 2 in 36% of the patients. With a median follow-up of 1126 days (range, 362 to 1469) for living patients, the overall survival was 50% and relapse-free survival was 43%. Of 7 deaths, 3 were due to relapse and 4 to transplantation-related complications. We conclude that 9 Gy TMI can be combined with myeloablative chemotherapy in the design of new preparative regimens for HSCT. This study was registered at clinicaltrials.gov as NCT00988013.
authors.affiliation: Division of Hematology/Oncology, University of Illinois Hospital and Health Sciences System, Chicago, Illinois; University of Illinois Cancer Center, Chicago, Illinois. Electronic address: prpatel8@uic.edu.
authors.forename: Pritesh
authors.initials: P
authors.lastname: Patel
authors.affiliation: Department of Radiation Oncology, University of Illinois Hospital and Health Sciences System, Chicago, Illinois; Department of Cellular and Radiation Oncology, University of Chicago, Chicago, Illinois.
authors.forename: Bulent
authors.initials: B
authors.lastname: Aydogan
authors.affiliation: University of Illinois Cancer Center, Chicago, Illinois; Department of Radiation Oncology, University of Illinois Hospital and Health Sciences System, Chicago, Illinois; Department of Cellular and Radiation Oncology, University of Chicago, Chicago, Illinois.
authors.forename: Matthew
authors.initials: M
authors.lastname: Koshy
authors.affiliation: Division of Hematology/Oncology, University of Illinois Hospital and Health Sciences System, Chicago, Illinois.
authors.forename: Dolores
authors.initials: D
authors.lastname: Mahmud
authors.affiliation: Division of Hematology/Oncology, University of Illinois Hospital and Health Sciences System, Chicago, Illinois.
authors.forename: Annie
authors.initials: A
authors.lastname: Oh
authors.affiliation: Division of Hematology/Oncology, University of Illinois Hospital and Health Sciences System, Chicago, Illinois; University of Illinois Cancer Center, Chicago, Illinois.
authors.forename: Santosh L
authors.initials: SL
authors.lastname: Saraf
authors.affiliation: Division of Hematology/Oncology, University of Illinois Hospital and Health Sciences System, Chicago, Illinois; University of Illinois Cancer Center, Chicago, Illinois.
authors.forename: John G
authors.initials: JG
authors.lastname: Quigley
authors.affiliation: Division of Hematology/Oncology, University of Illinois Hospital and Health Sciences System, Chicago, Illinois; University of Illinois Cancer Center, Chicago, Illinois.
authors.forename: Irum
authors.initials: I
authors.lastname: Khan
authors.affiliation: Department of Pharmacy Practice, University of Illinois at Chicago, Chicago, Illinois.
authors.forename: Karen
authors.initials: K
authors.lastname: Sweiss
authors.affiliation: Division of Hematology/Oncology, University of Illinois Hospital and Health Sciences System, Chicago, Illinois; University of Illinois Cancer Center, Chicago, Illinois.
authors.forename: Nadim
authors.initials: N
authors.lastname: Mahmud
authors.affiliation: Division of Hematology/Oncology, University of Illinois Hospital and Health Sciences System, Chicago, Illinois; University of Illinois Cancer Center, Chicago, Illinois.
authors.forename: David J
authors.initials: DJ
authors.lastname: Peace
authors.affiliation: Department of Radiation Oncology, University of Illinois Hospital and Health Sciences System, Chicago, Illinois; Department of Cellular and Radiation Oncology, University of Chicago, Chicago, Illinois.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: DeMasi
authors.affiliation: Department of Cellular and Radiation Oncology, University of Chicago, Chicago, Illinois.
authors.forename: Azhar M
authors.initials: AM
authors.lastname: Awan
authors.affiliation: Department of Radiation Oncology, University of Illinois Hospital and Health Sciences System, Chicago, Illinois; Department of Cellular and Radiation Oncology, University of Chicago, Chicago, Illinois.
authors.forename: Ralph R
authors.initials: RR
authors.lastname: Weichselbaum
authors.affiliation: Division of Hematology/Oncology, University of Illinois Hospital and Health Sciences System, Chicago, Illinois; University of Illinois Cancer Center, Chicago, Illinois. Electronic address: drond@uic.edu.
authors.forename: Damiano
authors.initials: D
authors.lastname: Rondelli
mesh_terms: D000328:Adult; D000368:Aged; D064591:Allografts; D002066:Busulfan / Q000008:administration & dosage; D005260:Female; D019337:Hematologic Neoplasms / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008297:Male; D008875:Middle Aged; D019653:Myeloablative Agonists / Q000008:administration & dosage; D036102:Peripheral Blood Stem Cell Transplantation; D019172:Transplantation Conditioning / Q000379:methods*; D061349:Unrelated Donors; D014916:Whole-Body Irradiation
chemical_list: D019653:Myeloablative Agonists; D002066:Busulfan
keywords: Allogeneic stem cell transplantation; Total marrow irradiation