title: Allogeneic marrow transplantation following cyclophosphamide and escalating doses of hyperfractionated total body irradiation in patients with advanced lymphoid malignancies: a Phase I/II trial.
abstract: OBJECTIVE
  To define the maximum tolerated dose (MTD) of unshielded total body irradiation (TBI) delivered from dual 60C sources at an exposure rate of 0.08 Gy/min and given in thrice daily fractions of 1.2 Gy in patients with advanced lymphoid malignancies.
  
  
  METHODS
  Forty-four patients with a median age of 28 (range 6-48) years were entered into a Phase I/II study. All patients received cyclophosphamide (CY), 120 mg/kg administered over 2 days before TBI. Marrow from human leukocyte antigen (HLA) identical siblings was infused following the last dose of TBI. An escalation-deescalation schema designed to not exceed an incidence of 25% of Grade 3-4 regimen-related toxicities (RRTs) was used. The first dose level tested was 13.2 Gy followed by 14.4 Gy.
  
  
  RESULTS
  None of the four patients at the dose level of 13.2 Gy developed Grade 3-4 RRT. Two of the first eight patients receiving 14.4 Gy developed Grade 3-4 RRT, establishing this as the MTD. An additional 32 patients were evaluated at the 14.4 Gy level to confirm these initial observations. Of 40 patients receiving 14.4 Gy, 13 (32.5%) developed Grade 3-4 RRTs; 46% in adults and 12% in children. The primary dose limiting toxicity was Grade 3-4 hepatic toxicity, which occurred in 12.5% of patients. Noninfectious Grade 3-4 interstitial pneumonia syndrome occurred in 5% of patients. The actuarial probabilities of event-free survival, relapse, and nonrelapse mortality at 2 years were 0.10, 0.81, and 0.47, respectively, for patients who received 14.4 Gy of TBI.
  
  
  CONCLUSIONS
  The outcome for patients receiving 14.4 Gy of TBI was not different from previous studies of other CY and TBI regimens in patients with advanced lymphoid malignancies. These data showed that the incidence of Grade 3-4 RRTs in adults was greater than the 25% maximum set as the goal of this study, suggesting that 13.2 Gy is a more appropriate dose of TBI for adults, while 14.4 Gy is an appropriate dose for children.
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, WA 98104, USA.
authors.forename: T
authors.initials: T
authors.lastname: Demirer
authors.forename: F B
authors.initials: FB
authors.lastname: Petersen
authors.forename: F R
authors.initials: FR
authors.lastname: Appelbaum
authors.forename: T A
authors.initials: TA
authors.lastname: Barnett
authors.forename: J
authors.initials: J
authors.lastname: Sanders
authors.forename: H J
authors.initials: HJ
authors.lastname: Deeg
authors.forename: R
authors.initials: R
authors.lastname: Storb
authors.forename: K
authors.initials: K
authors.lastname: Doney
authors.forename: W I
authors.initials: WI
authors.lastname: Bensinger
authors.forename: K
authors.initials: K
authors.lastname: Shannon-Dorcy
mesh_terms: D000293:Adolescent; D000328:Adult; D016026:Bone Marrow Transplantation; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000627:therapeutic use*; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy / Q000401:mortality / Q000532:radiotherapy*; D008875:Middle Aged; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000401:mortality / Q000532:radiotherapy*; D011879:Radiotherapy Dosage; D014184:Transplantation, Homologous; D014916:Whole-Body Irradiation
chemical_list: D003520:Cyclophosphamide