{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T20:45:14Z","timestamp":1792097114808,"version":"4.4.0"},"reference-count":50,"publisher":"American Society of Clinical Oncology (ASCO)","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["J Clin Oncol"],"abstract":"<jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>\n                      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 \u03b2-emitting radionuclides, attention is now shifting toward \u03b1-emitters, such as astatine-211 (\n                      <jats:sup>211<\/jats:sup>\n                      At), for their more potent and precise radiation delivery with minimized toxicity to surrounding tissues.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Patients and Methods<\/jats:title>\n                    <jats:p>\n                      To our knowledge, in this first-in-human, two-stage dose-finding study, we administered a single infusion of\n                      <jats:sup>211<\/jats:sup>\n                      At-labeled anti-CD45 monoclonal antibody before nonmyeloablative conditioning with fludarabine\/2-3 Gy total body irradiation and allografting from HLA-matched or single-allele\u2013mismatched donors in 45 adults (38-74 years of age) at a high relapse risk from myeloid malignancies or acute leukemia.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Seventeen patients were treated in stage I with 85-591 \u03bcCi\/kg of\n                      <jats:sup>211<\/jats:sup>\n                      At. The patient receiving 591 \u03bcCi\/kg developed veno-occlusive disease\/sinusoidal obstruction syndrome (VOD\/SOS), thereby establishing 500 \u03bcCi\/kg as the protocol-defined maximum tolerated dose and prompting initiation of stage II at that dose in 28 patients. Infusion reactions were mild.\n                      <jats:sup>211<\/jats:sup>\n                      At-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.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      <jats:sup>211<\/jats:sup>\n                      At-CD45 RIT can be incorporated into nonmyeloablative conditioning, with liver toxicity defining activity limits. Evidence of antitumor efficacy supports phase II evaluation.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/jco-26-00877","type":"journal-article","created":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T20:00:13Z","timestamp":1792094413000},"update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":0,"title":["First-In-Human Study of\n                    <sup>211<\/sup>\n                    At-CD45 Radioimmunotherapy With Nonmyeloablative Conditioning Hematopoietic Cell Transplantation for Adults With Hematologic Malignancies"],"prefix":"10.1200","author":[{"given":"Phuong T.","family":"Vo","sequence":"first","affiliation":[{"name":"Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA"},{"name":"Division of Hematology and Oncology, Department of Medicine, University of Washington, Seattle, 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