Allogeneic hematopoietic cell transplantation after conditioning with 131I-anti-CD45 antibody plus fludarabine and low-dose total body irradiation for elderly patients with advanced acute myeloid leukemia or high-risk myelodysplastic syndrome.

Publication Type:

Journal Article

Source:

Blood, Volume 114, Issue 27, p.5444-53 (2009)

Keywords:

2009, Acute Disease, Aged, Antibodies, Antibody Development Core Facility, Antigens, CD45, Biologics Production Core Facility, Cell Processing Core Facility, Center-Authored Paper, Clinical Research Division, Combined Modality Therapy, Female, Flow Cytometry Core Facility, Genomics Core Facility, hematopoietic stem cell transplantation, Humans, Iodine Radioisotopes, Leukemia, Myeloid, Male, Middle Aged, Myelodysplastic Syndromes, Research Trials Office Core Facility - Biostatistics Service, Risk Factors, Shared Resources, Survival Analysis, Survival Rate, TISSUE DISTRIBUTION, Transplantation Conditioning, Transplantation, Homologous, Treatment Outcome, Vidarabine, Whole-Body Irradiation

Abstract:

We conducted a study to estimate the maximum tolerated dose (MTD) of (131)I-anti-CD45 antibody (Ab; BC8) that can be combined with a standard reduced-intensity conditioning regimen before allogeneic hematopoietic cell transplantation. Fifty-eight patients older than 50 years with advanced acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS) were treated with (131)I-BC8 Ab and fludarabine plus 2 Gy total body irradiation. Eighty-six percent of patients had AML or MDS with greater than 5% marrow blasts at the time of transplantation. Treatment produced a complete remission in all patients, and all had 100% donor-derived CD3(+) and CD33(+) cells in the blood by day 28 after the transplantation. The MTD of (131)I-BC8 Ab delivered to liver was estimated to be 24 Gy. Seven patients (12%) died of nonrelapse causes by day 100. The estimated probability of recurrent malignancy at 1 year is 40%, and the 1-year survival estimate is 41%. These results show that CD45-targeted radiotherapy can be safely combined with a reduced-intensity conditioning regimen to yield encouraging overall survival for older, high-risk patients with AML or MDS. This study was registered at www.clinicaltrials.gov as #NCT00008177.