title: Non-myeloablative allogeneic hematopoietic cell transplantation following fludarabine plus 2 Gy TBI or ATG plus 8 Gy TLI: a phase II randomized study from the Belgian Hematological Society.
abstract: BACKGROUND
  Few studies thus far have compared head-to-head different non-myelooablative conditioning regimens for allogeneic hematopoietic cell transplantation (allo-HCT).
  
  
  METHODS
  Here, we report the results of a phase II multicenter randomized study comparing non-myeloablative allo-HCT from HLA-identical siblings (n = 54) or from 10/10 HLA-matched unrelated donors (n = 40) with either fludarabine plus 2 Gy total body irradiation (Flu-TBI arm; n = 49) or 8 Gy TLI + anti-thymocyte globulin (TLI-ATG arm; n = 45) conditioning.
  
  
  RESULTS
  The 180-day cumulative incidences of grade II-IV acute GVHD (primary endpoint) were 12.2% versus 8.9% in Flu-TBI and TLI-ATG patients, respectively (P = 0.5). Two-year cumulative incidences of moderate/severe chronic GVHD were 40.8% versus 17.8% in Flu-TBI and TLI-ATG patients, respectively (P = 0.017). Five Flu-TBI patients and 10 TLI-ATG patients received pre-emptive DLI for low donor chimerism levels, while 1 Flu-TBI patient and 5 TLI-ATG patients (including 2 patients given prior pre-emptive DLIs) received a second HCT for poor graft function, graft rejection, or disease progression. Four-year cumulative incidences of relapse/progression were 22% and 50% in Flu-TBI and TLI-ATG patients, respectively (P = 0.017). Four-year cumulative incidences of nonrelapse mortality were 24% and 13% in Flu-TBI and TLI-ATG patients, respectively (P = 0.5). Finally, 4-year overall (OS) and progression-free survivals (PFS) were 53% and 54%, respectively, in the Flu-TBI arm, versus 54% (P = 0.9) and 37% (P = 0.12), respectively, in the TLI-ATG arm.
  
  
  CONCLUSIONS
  In comparison to patients included in the Flu-TBI arm, patients included in the TLI-ATG arm had lower incidence of chronic GVHD, higher incidence of relapse and similar OS.
  
  
  BACKGROUND
  The study was registered on ClinicalTrial.gov ( NCT00603954 ) and EUDRACT (2010-024297-19) .
authors: Department of Hematology, University of Liège, and CHU of Liège, Sart-Tilman, 4000, Liège, Belgium. f.baron@ulg.ac.be.
authors: Frédéric
authors: F
authors: Baron
authors: ZNA Stuivenberg, Antwerpen, Belgium. Pierre.Zachee@zna.be.
authors: Pierre
authors: P
authors: Zachée
authors: AZ Gasthuisberg Leuven, Leuven, Belgium. johan.maertens@uzleuven.be.
authors: Johan
authors: J
authors: Maertens
authors: Ghent University Hospital, Ghent, Belgium. Tessa.Kerre@UGent.be.
authors: Tessa
authors: T
authors: Kerre
authors: Department of Hematology, University of Liège, and CHU of Liège, Sart-Tilman, 4000, Liège, Belgium. aurelie.ory@chu.ulg.ac.be.
authors: Aurélie
authors: A
authors: Ory
authors: Department of Statistics, University of Liège, and CHU of Liège, Liège, Belgium. laurence.seidel@chu.ulg.ac.be.
authors: Laurence
authors: L
authors: Seidel
authors: Mont-Godine University Hospital (UCL), Yvoir, Belgium. carlos.graux@uclouvain.be.
authors: Carlos
authors: C
authors: Graux
authors: Jules Bordet Institute (ULB), Bruxelles, Belgium. philippe.lewalle@bordet.be.
authors: Philippe
authors: P
authors: Lewalle
authors: Maastricht University Medical Center, Maastricht, The Netherlands. m.van.gelder@mumc.nl.
authors: Michel
authors: M
authors: Van Gelder
authors: Jessa Ziekenhuis, Hasselt, Belgium. Koen.Theunissen@virgajesse.be.
authors: Koen
authors: K
authors: Theunissen
authors: Department of Hematology, University of Liège, and CHU of Liège, Sart-Tilman, 4000, Liège, Belgium. e.willems@chu.ulg.ac.be.
authors: Evelyne
authors: E
authors: Willems
authors: HLA Red Cross Flanders, Mechelen, Belgium. Marie-Paule.Emonds@rodekruis.be.
authors: Marie-Paule
authors: MP
authors: Emonds
authors: Universitair Ziekenhuis Brussel (UZ Brussels), Brussels, Belgium. Ann.DeBecker@uzbrussel.be.
authors: Ann
authors: A
authors: De Becker
authors: Department of Hematology, University of Liège, and CHU of Liège, Sart-Tilman, 4000, Liège, Belgium. yves.beguin@chu.ulg.ac.be.
authors: Yves
authors: Y
authors: Beguin
mesh_terms: D000328:Adult; D000368:Aged; D064591:Allografts; D000961:Antilymphocyte Serum / Q000008:administration & dosage; D000970:Antineoplastic Agents / Q000008:administration & dosage; D059248:Chemoradiotherapy; D018572:Disease-Free Survival; D005260:Female; D006086:Graft vs Host Disease / Q000453:epidemiology / Q000517:prevention & control*; D019337:Hematologic Neoplasms / Q000401:mortality / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods* / Q000401:mortality; D006801:Humans; D015994:Incidence; D008297:Male; D008320:Maltose / Q000008:administration & dosage / Q000031:analogs & derivatives; D008875:Middle Aged; D019172:Transplantation Conditioning / Q000379:methods*; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives; D014916:Whole-Body Irradiation
chemical_list: D000961:Antilymphocyte Serum; D000970:Antineoplastic Agents; C462079:aurothiomaltose; D008320:Maltose; D014740:Vidarabine; C024352:fludarabine
references: Blood. 2005 Oct 15;106(8):2912-9
references: 15994282
references: Curr Opin Hematol. 2005 Nov;12(6):435-43
references: 16217159
references: Biol Blood Marrow Transplant. 2005 Dec;11(12):945-56
references: 16338616
references: Biol Blood Marrow Transplant. 2006 Apr;12(4):454-65
references: 16545729
references: Biol Blood Marrow Transplant. 2006 May;12(5):573-84
references: 16635793
references: Haematologica. 2007 Jul;92(7):1004-6
references: 17606460
references: Biol Blood Marrow Transplant. 2007 Sep;13(9):1041-8
references: 17697966
references: Blood. 2007 Oct 1;110(7):2744-8
references: 17595333
references: Biol Blood Marrow Transplant. 2009 May;15(5):580-8
references: 19361750
references: Blood. 2009 Jul 30;114(5):1099-109
references: 19423725
references: Eur J Immunol. 2010 Jul;40(7):1862-9
references: 20583031
references: Leukemia. 2010 Nov;24(11):1852-8
references: 20827288
references: Blood. 2011 Jun 9;117(23):6375-82
references: 21467544
references: JAMA. 2011 Nov 2;306(17):1874-83
references: 22045765
references: Blood. 2012 Jun 21;119(25):6145-54
references: 22563089
references: Biol Blood Marrow Transplant. 2012 Oct;18(10):1600-7
references: 22484666
references: Blood. 2001 Jun 1;97(11):3390-400
references: 11369628
references: J Clin Oncol. 2005 Mar 20;23(9):1993-2003
references: 15774790
references: N Engl J Med. 2005 Sep 29;353(13):1321-31
references: 16192477
references: Leukemia. 2012 Dec;26(12):2462-8
references: 22699419
references: Cancer. 2013 Feb 1;119(3):602-11
references: 22893313
references: J Clin Oncol. 2013 Apr 20;31(12):1530-8
references: 23478054
references: Biol Blood Marrow Transplant. 2013 Sep;19(9):1340-7
references: 23769990
references: Bone Marrow Transplant. 2014 Mar;49(3):389-96
references: 24419525
references: Biol Blood Marrow Transplant. 2014 Jun;20(6):837-43
references: 24607552
references: Biol Blood Marrow Transplant. 2014 Aug;20(8):1156-62
references: 24727330
references: Haematologica. 2014 Oct;99(10):1624-31
references: 25085357