title: Modified total body irradiation as a planned second high-dose therapy with stem cell infusion for patients with bone-based malignancies.
abstract: OBJECTIVE
  To estimate the maximum tolerated dose of hyperfractionated total marrow irradiation (TMI) as a second consolidation after high-dose chemotherapy with autologous or syngeneic blood stem cell transfusion for patients with bone/bone marrow-based malignant disease.
  
  
  METHODS
  Fifty-seven patients aged 3-65 years (median, 45 years), including 21 with multiple myeloma, 24 with breast cancer, 10 with sarcoma, and 2 with lymphoma, were treated with 1.5 Gy administered twice daily to a total dose of 12 Gy (n = 27), 13.5 Gy (n = 12), and 15 Gy (n = 18). Median time between the 2 transplants was 105 days (range, 63-162 days).
  
  
  RESULTS
  All patients engrafted neutrophils (median, Day 11; range, Day 9-23) and became platelet independent (median, Day 9; range, Day 7-36). There were 5 cases of Grade 3-4 regimen-related pulmonary toxicity, 1 at 12 Gy, and 4 at 15 Gy. Complete responses, partial responses, and stabilizations were achieved in 33%, 26%, and 41% of patients, respectively. Kaplan-Meier estimates of 5-year progression-free survival and overall survival for 56 evaluable patients are 24% and 36%, respectively. Median time of follow-up among survivors was 96 months (range, 77-136 months).
  
  
  CONCLUSIONS
  Total marrow irradiation as a second myeloablative therapy is feasible. The estimated maximum tolerated dose for TMI in a tandem transplant setting was 13.5 Gy. Because 20% of patients are surviving at 8 years free of disease, further studies of TMI are warranted.
authors.affiliation: Fred Hutchinson Cancer Research Center, University of Washington, Clinical Research Division, Seattle, WA 98109-1024, USA.
authors.forename: Renata E
authors.initials: RE
authors.lastname: Zaucha
authors.forename: Dean C
authors.initials: DC
authors.lastname: Buckner
authors.forename: Todd
authors.initials: T
authors.lastname: Barnett
authors.forename: Leona A
authors.initials: LA
authors.lastname: Holmberg
authors.forename: Ted
authors.initials: T
authors.lastname: Gooley
authors.forename: Heather A
authors.initials: HA
authors.lastname: Hooper
authors.forename: David G
authors.initials: DG
authors.lastname: Maloney
authors.forename: Frederick
authors.initials: F
authors.lastname: Appelbaum
authors.forename: William I
authors.initials: WI
authors.lastname: Bensinger
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019046:Bone Marrow Neoplasms / Q000188:drug therapy / Q000532:radiotherapy* / Q000556:secondary; D001859:Bone Neoplasms / Q000188:drug therapy / Q000532:radiotherapy* / Q000556:secondary; D001943:Breast Neoplasms / Q000532:radiotherapy; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009101:Multiple Myeloma / Q000532:radiotherapy; D011832:Radiation Injuries / Q000209:etiology; D011879:Radiotherapy Dosage; D016019:Survival Analysis; D014916:Whole-Body Irradiation / Q000009:adverse effects / Q000379:methods*