Pilot study of a (213)bismuth-labeled anti-CD45 mAb as a novel nonmyeloablative conditioning for DLA-haploidentical littermate hematopoietic transplantation.
BACKGROUND
A pilot study was conducted to determine whether conditioning using selective targeting of hematopoietic cells with an alpha-particle emitter, bismuth-213 ((213)Bi)-labeled anti-CD45 monoclonal antibody (mAb) is sufficient to overcome the major histocompatibility barrier in a canine model of dog leukocyte antigen-haploidentical hematopoietic cell transplantation (HCT).


METHODS
Six dogs were administered 0.5 mg/kg (213)Bi-labeled anti-CD45 mAb (dose (213)Bi=2.26-4.9 mCi/kg) in six to eight injections. For postgrafting immunosuppression, all dogs received cyclosporine and mycophenolate mofetil.


RESULTS
All dogs had initial donor engraftment, with three of six dogs having sustained engraftment to last point of follow-up. Two dogs receiving 2.26 and 3.25 mCi/kg of (213)Bi rejected their grafts at day +127 and +125, respectively, whereas dogs receiving (213)Bi doses of 3.3 mCi/kg or greater achieved high level donor chimerism.


CONCLUSIONS
The results suggest that nonmyeloablative conditioning with (213)Bi-labeled anti-CD45 mAb could be applicable to major histocompatibility haploidentical HCT without excessive nonhematologic regimen-related toxicity.
Nakamae
Hirohisa
H
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024, USA.
Kerbauy
Fabio R
FR
Wilbur
D Scott
DS
Bethge
Wolfgang
W
Hamlin
Donald K
DK
Santos
Erlinda B
EB
Storb
Rainer
R
Sandmaier
Brenda M
BM
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001729:Bismuth; D017077:Culture Media, Conditioned; D004285:Dogs; D006085:Graft Survival / Q000276:immunology*; D006238:Haploidy; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D017493:Leukocyte Common Antigens / Q000276:immunology*; D009504:Neutrophils / Q000166:cytology; D011868:Radioisotopes; D013921:Thrombocytopenia / Q000453:epidemiology; D014184:Transplantation, Homologous / Q000276:immunology / Q000379:methods
D000911:Antibodies, Monoclonal; D017077:Culture Media, Conditioned; D011868:Radioisotopes; D017493:Leukocyte Common Antigens; D001729:Bismuth