title: Fludarabine and 2-Gy TBI is superior to 2 Gy TBI as conditioning for HLA-matched related hematopoietic cell transplantation: a phase III randomized trial.
abstract: The risks and benefits of adding fludarabine to a 2-Gy total body irradiation (TBI) nonmyeloablative regimen are unknown. For this reason, we conducted a prospective randomized trial comparing 2-Gy TBI alone, or in combination with 90 mg/m(2) fludarabine (FLU/TBI), before transplantation of peripheral blood stem cells from HLA-matched related donors. Eighty-five patients with hematological malignancies were randomized to be conditioned with TBI alone (n = 44) or FLU/TBI (n = 41). All patients had initial engraftment. Two graft rejections were observed, both in the TBI group. Infection rates, nonrelapse mortality, and graft-versus-host disease (GVHD) were similar between groups. Three-year overall survival was lower in the TBI group (54% versus 65%; hazard ratio [HR], .57; P = .09), with higher incidences of relapse/progression (55% versus 40%; HR, .55; P = .06), relapse-related mortality (37% versus 28%; HR, .53; P = .09), and a lower progression-free survival (36% versus 53%; HR, .56; P = .05). Median donor T cell chimerism levels were significantly lower in the TBI group at days 28 (61% versus 90%; P < .0001) and 84 (68% versus 92%; P < .0001), as was NK cell chimerism on day 28 (75% versus 96%; P = .0005). In conclusion, this randomized trial demonstrates the importance of fludarabine in augmenting the graft-versus-tumor effect by ensuring prompt and durable high-level donor engraftment early after transplantation.
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Kornblit
authors.forename: David G
authors.initials: DG
authors.lastname: Maloney
authors.forename: Rainer
authors.initials: R
authors.lastname: Storb
authors.forename: Jan
authors.initials: J
authors.lastname: Storek
authors.forename: Parameswaran
authors.initials: P
authors.lastname: Hari
authors.forename: Vladan
authors.initials: V
authors.lastname: Vucinic
authors.forename: Richard T
authors.initials: RT
authors.lastname: Maziarz
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Chauncey
authors.forename: Michael A
authors.initials: MA
authors.lastname: Pulsipher
authors.forename: Benedetto
authors.initials: B
authors.lastname: Bruno
authors.forename: Finn B
authors.initials: FB
authors.lastname: Petersen
authors.forename: Wolfgang A
authors.initials: WA
authors.lastname: Bethge
authors.forename: Kai
authors.initials: K
authors.lastname: Hübel
authors.forename: Michelle E
authors.initials: ME
authors.lastname: Bouvier
authors.forename: Takahiro
authors.initials: T
authors.lastname: Fukuda
authors.forename: Barry E
authors.initials: BE
authors.lastname: Storer
authors.forename: Brenda M
authors.initials: BM
authors.lastname: Sandmaier
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D005260:Female; D006680:HLA Antigens / Q000235:genetics / Q000378:metabolism*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D016130:Immunophenotyping; D008297:Male; D008875:Middle Aged; D019172:Transplantation Conditioning / Q000379:methods*; D014740:Vidarabine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D014916:Whole-Body Irradiation / Q000379:methods*; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D006680:HLA Antigens; D014740:Vidarabine; C024352:fludarabine
keywords: Fludarabine/low dose total body irradiation; HLA-matched related hematopoietic cell transplantation randomized trial; Nonmyeloablative conditioning