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: 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
• Journal: Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation (Biol Blood Marrow Transplant) Vol. 19 Issue 9 Pg. 1340-7 (Sep 2013) ISSN: 1523-6536 [Electronic] United States
• PMID: 23769990 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Chemical References

• Antineoplastic Agents
• HLA Antigens
• Vidarabine
• fludarabine

Topics

• Adolescent
• Adult
• Aged
• Antineoplastic Agents (therapeutic use)
• Female
• HLA Antigens (genetics, metabolism)
• Hematopoietic Stem Cell Transplantation (methods)
• Humans
• Immunophenotyping
• Male
• Middle Aged
• Transplantation Conditioning (methods)
• Vidarabine (analogs & derivatives, therapeutic use)
• Whole-Body Irradiation (methods)
• Young Adult