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: Few studies thus far have compared head-to-head different non-myelooablative conditioning regimens for allogeneic hematopoietic cell transplantation (allo-HCT).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.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.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.The study was registered on ClinicalTrial.gov ( NCT00603954 ) and EUDRACT (2010-024297-19) .

SUBMITTER: Baron F 

PROVIDER: S-EPMC4332717 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature