Fludarabine and 2-Gy TBI is superior to 2Gy TBI as conditioning for HLA-Matched related hematopoietic cell transplantation: A phase III randomized trial

Brian Kornblit, David G. Maloney, Rainer Storb, Jan Storek, Parameswaran Hari, Vladan Vucinic, Richard T. Maziarz, Thomas R. Chauncey, Michael A. Pulsipher, Benedetto Bruno, Finn B. Petersen, Wolfgang A. Bethge, Kai Hübel, Michelle E. Bouvier, Takahiro Fukuda, Barry E. Storer, Brenda M. Sandmaier

Research output: Contribution to journalArticle

12 Scopus citations

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 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.

Original languageEnglish (US)
Pages (from-to)1340-1347
Number of pages8
JournalBiology of Blood and Marrow Transplantation
Volume19
Issue number9
DOIs
StatePublished - Sep 1 2013

Keywords

  • Body irradiation
  • Fludarabine/low dose total
  • HLA-matched related
  • Hematopoietic cell
  • Nonmyeloablative conditioning
  • Transplantation randomized
  • Trial

ASJC Scopus subject areas

  • Hematology
  • Transplantation

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  • Cite this

    Kornblit, B., Maloney, D. G., Storb, R., Storek, J., Hari, P., Vucinic, V., Maziarz, R. T., Chauncey, T. R., Pulsipher, M. A., Bruno, B., Petersen, F. B., Bethge, W. A., Hübel, K., Bouvier, M. E., Fukuda, T., Storer, B. E., & Sandmaier, B. M. (2013). Fludarabine and 2-Gy TBI is superior to 2Gy TBI as conditioning for HLA-Matched related hematopoietic cell transplantation: A phase III randomized trial. Biology of Blood and Marrow Transplantation, 19(9), 1340-1347. https://doi.org/10.1016/j.bbmt.2013.06.002