Pilot study of a (213)bismuth-labeled anti-CD45 mAb as a novel nonmyeloablative conditioning for DLA-haploidentical littermate hematopoietic transplantation

Abstract

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.

Conclusion: 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.

Figure 1

A) Peripheral blood absolute neutrophil (ANC), lymphocyte (ALC), platelet counts (PLT) and mononuclear cell (MNC) donor chimerism of dogs which underwent nonmyeloablative dog lymphocyte antigen-haploidentical hematopoietic cell transplantation. ANC, ALC and PLT of peripheral blood in the 6 dogs which received total doses of 2.26–4.9 mCi/kg ²¹³Bi labeled anti-CD45 monoclonal antibody as nonmyeloablative conditioning. B) Liver enzymes and creatinine levels in the dogs treated with nonmyeloablative dog lymphocyte antigen-haploidentical hematopoietic cell transplantation (HCT). Values of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (AP) and creatinine in the 6 dogs which received nonmyeloablative dog lymphocyte antigen-haploidentical HCT.