Fabio R Kerbauy

Publications (2)8.01 Total impact

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

  Hirohisa Nakamae, Fabio R Kerbauy, D Scott Wilbur, Wolfgang Bethge, Donald K Hamlin, Erlinda B Santos, Rainer Storb, Brenda M Sandmaier
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  ABSTRACT: 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). 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. 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. 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.
  Transplantation 03/2010; 89(11):1336-40. · 4.00 Impact Factor
• Article: Dog leukocyte antigen-haploidentical stem cell allografts after anti-CD44 therapy and nonmyeloablative conditioning in a preclinical canine model.

  Takahiro Fukuda, Fabio R Kerbauy, Theodore Gooley, Erlinda B Santos, Rainer Storb, Brenda M Sandmaier
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  ABSTRACT: We previously described a reduced-intensity hematopoietic cell transplantation (HCT) regimen in dog leukocyte antigen (DLA)-haploidentical littermate recipients consisting of 450 cGy total body irradiation (TBI) and anti-CD44 monoclonal antibody (mAb) S5 before and mycophenolate mofetil (MMF)/cyclosporine (CSP) after HCT. We tested a nonmyeloablative regimen of mAb S5 and 200 cGy TBI with postgrafting MMF/CSP in 44 DLA-haploidentical recipients using eight different regimens. Ten dogs also received escalating doses of donor lymphocyte infusion (DLI) alone or with pentostatin to convert to complete donor chimerism. All dogs achieved initial engraftment between one to two weeks after HCT with peripheral blood mononuclear cell (PBMC) donor chimerism ranging from 2% to 98% (median 37%) on day +35. Twenty-five (57%) dogs rejected their donor grafts at a median of seven (range; 1-19) weeks after HCT. Low levels of PBMC donor chimerism at three weeks predicted graft rejection. DLI neither facilitated conversion to full donor chimerism after HCT nor prevented rejection. Higher total nucleated cells, CD4+, CD8+, and CD14+ cell subset numbers in the PBMC graft were associated with stable full donor engraftment. Dogs given higher cell subset doses of infused PBMC achieved longer duration of mixed chimerism. Nonmyeloablative conditioning with 200 cGy TBI and anti-CD44 mAb was sufficient for initial uniform engraftment across DLA haplotype-mismatched barriers. However, sustained donor engraftment was seen in only 43% of recipients. Graft composition and donor-dominant chimerism early after HCT may be the most important factors for sustained donor engraftment.
  Transplantation 09/2006; 82(3):332-9. · 4.00 Impact Factor