188Re-labeled anti-CD66 monoclonal antibody in stem cell transplantation for patients with high-risk acute myeloid leukemia

Abstract

We have intensified the conditioning regimen prior to stem cell transplantation in 57 patients with high-risk AML and MDS by treating patients with a 188Re-labeled anti-CD66 monoclonal antibody. Dosimetry was performed prior to therapy and a favorable dosimetry was observed in all cases. Radioimmunotherapy with the labeled antibody provided a mean of 15.5 Gy of additional radiation to the marrow, the kidney was the normal organ receiving the highest dose of supplemental radiation (mean 7.4 Gy): Radioimmunotherapy was followed by standard full-dose conditioning with total body irradiation (12 Gy) (n = 30) or busulfan (n = 27) and high-dose cyclophosphamide +/- thiotepa. Patients subsequently received a T cell depleted allogeneic graft from a HLA-compatible family donor (n = 24), a matched unrelated donor (n = 23) or a haploidentical family donor (n = 6). In four patients, an unmanipulated autologous graft was used. Infusion-related toxicity due to the labeled antibody was minimal and no increase in treatment-related mortality due to the radioimmunoconjugate was observed. Day +30 and day +100 mortalities were 3 and 7%, respectively, and after a median follow-up of 26 months treatment-related mortality was 30%. Late renal toxicity was observed in 14% of patients. The disease-free survival rate for 44 patients in 1 or 2 CR or in very good PR (< 15% blasts in the marrow at transplant) is 64% with only 8% disease-free survival for those with > 15% blasts in the marrow at transplant.