Pilot Study of a 213Bismuth-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 a-particle emitter, bismuth-213 ( super(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 super(213)Bi-labeled anti-CD45 mAb (dose super(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 super(213)Bi rejected their grafts at day +127 and +125, respectively, whereas dogs receiving super(213)Bi doses of 3.3 mCi/kg or greater achieved high level donor chimerism. Conclusion. The results suggest that nonmyeloablative conditioning with super(213)Bi-labeled anti-CD45 mAb could be applicable to major histocompatibility haploidentical HCT without excessive nonhematologic regimen-related toxicity.