Relapse is the dominant cause of failure after allogeneic hematopoietic cell transplantation (HCT) for aggressive hematologic malignancies. CD45-directed radioimmunotherapy (RIT) has been investigated to intensify conditioning and augment antitumor efficacy. After gaining clinical experience with β-emitting radionuclides, attention is now shifting toward α-emitters, such as astatine-211 (211At), for their more potent and precise radiation delivery with minimized toxicity to surrounding tissues.
Seventeen patients were treated in stage I with 85-591 μCi/kg of 211At. The patient receiving 591 μCi/kg developed veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS), thereby establishing 500 μCi/kg as the protocol-defined maximum tolerated dose and prompting initiation of stage II at that dose in 28 patients. Infusion reactions were mild. 211At-CD45 RIT did not delay hematopoietic recovery, impair donor chimerism, or increase graft-versus-host disease (GVHD) rates. In stage II, six patients (all receiving sirolimus as part of GVHD prophylaxis for unrelated donor HCT) experienced VOD/SOS. Among the 13 patients with circulating blasts at baseline, blasts cleared in 12 before initiation of fludarabine/total body irradiation, demonstrating immediate cytotoxic activity. Estimated 1-year relapse-free and overall survival were 42% (95% CI, 28%-56%) and 49% (34%-62%), respectively.
Journal of Clinical Oncology
Journal Name
Journal of Clinical Oncology
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