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

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.

Figures

Figure 1

Estimated radiation absorbed doses per millicurie of 131I. Estimated radiation absorbed doses per millicurie of 131I administered for (A) all patients, (B) patients with AML in remission, in relapse, with refractory AML, and patients with high-risk MDS. Results are shown as mean ± SEM.

Figure 2

The fitted dose-toxicity curve from the observed data. The solid circles indicate the observed DLT rate at the appropriate dose, and the vertical line represents the dose associated with a DLT rate of 25% from the fitted curve.

Figure 3

Estimates of the probability of OS, DFS, NRM, and relapse among all patients who received a therapeutic dose of 131I-BC8 Ab, followed by TBI/FLU.

Figure 4

Estimates of the probability of OS, DFS, NRM, and relapse among patients treated at the MTD of 24 Gy of radiation delivered to the liver by the 131I-BC8 Ab, followed by TBI/FLU.