TY - JOUR
T1 - Fludarabine and 2-Gy TBI is superior to 2Gy TBI as conditioning for HLA-Matched related hematopoietic cell transplantation
T2 - A phase III randomized trial
AU - Kornblit, Brian
AU - Maloney, David G.
AU - Storb, Rainer
AU - Storek, Jan
AU - Hari, Parameswaran
AU - Vucinic, Vladan
AU - Maziarz, Richard T.
AU - Chauncey, Thomas R.
AU - Pulsipher, Michael A.
AU - Bruno, Benedetto
AU - Petersen, Finn B.
AU - Bethge, Wolfgang A.
AU - Hübel, Kai
AU - Bouvier, Michelle E.
AU - Fukuda, Takahiro
AU - Storer, Barry E.
AU - Sandmaier, Brenda M.
N1 - Funding Information:
Financial disclosure: Research funding was provided by the National Institutes of Health , Bethesda, MD, grants, CA078902 , HL036444 , and CA015704 . The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health nor its subsidiary Institutes and Centers. B.K. was supported by a fellowship from the Danish Cancer Society (DP08135), Frøken Amalie Jørgensens Mindelegat and Anders Hasselbalchs Fond. B.B. was supported by Ricerca Sanitaria Finalizzata RF-PIE-2008-1206999 and RF-PIE-2009-1491359 .
PY - 2013/9
Y1 - 2013/9
N2 - 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 90mg/m2 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.
AB - 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 90mg/m2 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.
KW - Body irradiation
KW - Fludarabine/low dose total
KW - HLA-matched related
KW - Hematopoietic cell
KW - Nonmyeloablative conditioning
KW - Transplantation randomized
KW - Trial
UR - http://www.scopus.com/inward/record.url?scp=84882781560&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84882781560&partnerID=8YFLogxK
U2 - 10.1016/j.bbmt.2013.06.002
DO - 10.1016/j.bbmt.2013.06.002
M3 - Article
C2 - 23769990
AN - SCOPUS:84882781560
SN - 1083-8791
VL - 19
SP - 1340
EP - 1347
JO - Biology of Blood and Marrow Transplantation
JF - Biology of Blood and Marrow Transplantation
IS - 9
ER -