Blood Transfusion Research Today is a free monthly online journal that collates and summarizes the latest research about Blood Transfusion, including details on blood donation, blood types, leukemia.

CD154 blockade and donor-specific transfusions in DLA-identical marrow transplantation in dogs conditioned with 1-Gy total body irradiation.

Jochum C, Beste M, Zellmer E, Graves SS, Storb R

Transplantation Biology Program, Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109-1024, USA.

Stable mixed donor/host chimerism has been reliably established in dogs given a sublethal dose (2 Gy) of total body irradiation (TBI) before and immunosuppression with mycophenolate mofetil (MMF) or rapamycin combined with cyclosporine (CSP) after marrow transplantation from dog leukocyte antigen (DLA)-identical littermates (hematopoietic cell transplantation [HCT]). When TBI was reduced to 1 Gy, only transient engraftment was observed. Here we investigated whether stable engraftment after 1-Gy TBI could be accomplished by reducing host-versus-donor immune responsiveness through preceding CD154 blockade and infusion of donor peripheral blood mononuclear cells (PBMCs). We found that the anti-human CD154 antibody, 5c8, cross-reacted with canine lymphocytes and blocked alloimmune responses in vitro. Based on pharmacokinetic studies, 6 dogs received a single intravenous injection of 5 mg/kg anti-CD154 antibody (on day -5), followed 1 day later by donor PBMCs. On day 0, the dogs were given 1 Gy of TBI and underwent DLA-identical marrow grafts. Postgraft immunosuppression consisted of MMF and CSP. All 6 dogs demonstrated initial engraftment; 3 dogs sustained the engraftment for >26 weeks, whereas 3 dogs rejected their grafts, after 9, 22, and 24 weeks, and survived with autologous recovery. Graft survival was significantly improved over that in 11 historical controls conditioned with 1-Gy TBI and given either MMF or rapamycin with CSP after HCT, all of which rejected their grafts between 3 and 12 weeks (P = .03). Preceding donor PBMC infusion and CD154 blockade improved survival of DLA-identical marrow grafts after 1-Gy TBI.

Published 23 January 2007 in Biol Blood Marrow Transplant, 13(2): 164-71.
Full-text of this article is available online (may require subscription).

© 2004-2008 Blood Transfusion Research Today. All Rights Reserved.