{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T04:43:51Z","timestamp":1774413831029,"version":"3.50.1"},"reference-count":42,"publisher":"American Society of Hematology","issue":"7","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2003,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Holmium-166 1, 4, 7, 10-tetraazcyclododecane-1, 4, 7, 10-tetramethylenephosphonate (166Ho-DOTMP) is a radiotherapeutic that localizes specifically to the skeleton and can deliver high-dose radiation to the bone and bone marrow. In patients with multiple myeloma undergoing autologous hematopoietic stem cell transplantation two phase 1\/2 dose-escalation studies of high-dose 166Ho-DOTMP plus melphalan were conducted. Patients received a 30 mCi (1.110 Gbq) tracer dose of 166Ho-DOTMP to assess skeletal uptake and to calculate a patient-specific therapeutic dose to deliver a nominal radiation dose of 20, 30, or 40 Gy to the bone marrow. A total of 83 patients received a therapeutic dose of 166Ho-DOTMP followed by autologous hematopoietic stem cell transplantation 6 to 10 days later. Of the patients, 81 had rapid and sustained hematologic recovery, and 2 died from infection before day 60. No grades 3 to 4 nonhematologic toxicities were reported within the first 60 days. There were 27 patients who experienced grades 2 to 3 hemorrhagic cystitis, only 1 of whom had received continuous bladder irrigation. There were 7 patients who experienced complications considered to be caused by severe thrombotic microangiopathy (TMA). No cases of severe TMA were reported in patients receiving in 166Ho-DOMTP doses lower than 30 Gy. Approximately 30% of patients experienced grades 2 to 4 renal toxicity, usually at doses targeting more than 40 Gy to the bone marrow. Complete remission was achieved in 29 (35%) of evaluable patients. With a minimum follow-up of 23 months, the median survival had not been reached and the median event-free survival was 22 months. 166Ho-DOTMP is a promising therapy for patients with multiple myeloma and merits further evaluation. (Blood. 2003;102:2684-2691)<\/jats:p>","DOI":"10.1182\/blood-2002-10-3250","type":"journal-article","created":{"date-parts":[[2003,5,6]],"date-time":"2003-05-06T00:14:56Z","timestamp":1052180096000},"page":"2684-2691","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":101,"title":["166Ho-DOTMP plus melphalan followed by peripheral blood stem cell transplantation in patients with multiple myeloma: results of two phase 1\/2 trials"],"prefix":"10.1182","volume":"102","author":[{"given":"Sergio","family":"Giralt","sequence":"first","affiliation":[{"name":"From the MD Anderson Cancer Center, Houston, TX; the Fred Hutchinson Cancer Research Center; the University of Miami Medical Center, Miami, FL; the University of Washington Medical Center; and NeoRx, Seattle, WA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William","family":"Bensinger","sequence":"additional","affiliation":[{"name":"From the MD Anderson Cancer Center, Houston, TX; the Fred Hutchinson Cancer Research Center; the University of Miami Medical Center, Miami, FL; the University of Washington Medical Center; and NeoRx, Seattle, WA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark","family":"Goodman","sequence":"additional","affiliation":[{"name":"From the MD Anderson Cancer Center, Houston, TX; the Fred Hutchinson Cancer Research Center; the University of Miami Medical Center, Miami, FL; the University of Washington Medical Center; and NeoRx, Seattle, WA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Donald","family":"Podoloff","sequence":"additional","affiliation":[{"name":"From the MD Anderson Cancer Center, Houston, TX; the Fred Hutchinson Cancer Research Center; the University of Miami Medical Center, Miami, FL; the University of Washington Medical Center; and NeoRx, Seattle, WA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janet","family":"Eary","sequence":"additional","affiliation":[{"name":"From the MD Anderson Cancer Center, Houston, TX; the Fred Hutchinson Cancer Research Center; the University of Miami Medical Center, Miami, FL; the University of Washington Medical Center; and NeoRx, Seattle, WA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard","family":"Wendt","sequence":"additional","affiliation":[{"name":"From the MD Anderson Cancer Center, Houston, TX; the Fred Hutchinson Cancer Research Center; the University of Miami Medical Center, Miami, FL; the University of Washington Medical Center; and NeoRx, Seattle, WA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raymond","family":"Alexanian","sequence":"additional","affiliation":[{"name":"From the MD Anderson Cancer Center, Houston, TX; the Fred Hutchinson Cancer Research Center; the University of Miami Medical Center, Miami, FL; the University of Washington Medical Center; and NeoRx, Seattle, WA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Donna","family":"Weber","sequence":"additional","affiliation":[{"name":"From the MD Anderson Cancer Center, Houston, TX; the Fred Hutchinson Cancer Research Center; the University of Miami Medical Center, Miami, FL; the University of Washington Medical Center; and NeoRx, Seattle, WA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Maloney","sequence":"additional","affiliation":[{"name":"From the MD Anderson Cancer Center, Houston, TX; the Fred Hutchinson Cancer Research Center; the University of Miami Medical Center, Miami, FL; the University of Washington Medical Center; and NeoRx, Seattle, WA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leona","family":"Holmberg","sequence":"additional","affiliation":[{"name":"From the MD Anderson Cancer Center, Houston, TX; the Fred Hutchinson Cancer Research Center; the University of Miami Medical Center, Miami, FL; the University of Washington Medical Center; and NeoRx, Seattle, WA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph","family":"Rajandran","sequence":"additional","affiliation":[{"name":"From the MD Anderson Cancer Center, Houston, TX; the Fred Hutchinson Cancer Research Center; the University of Miami Medical Center, Miami, FL; the University of Washington Medical Center; and NeoRx, Seattle, WA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hazel","family":"Breitz","sequence":"additional","affiliation":[{"name":"From the MD Anderson Cancer Center, Houston, TX; the Fred Hutchinson Cancer Research Center; the University of Miami Medical Center, Miami, FL; the University of Washington Medical Center; and NeoRx, Seattle, WA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard","family":"Ghalie","sequence":"additional","affiliation":[{"name":"From the MD Anderson Cancer Center, Houston, TX; the Fred Hutchinson Cancer Research Center; the University of Miami Medical Center, Miami, FL; the University of Washington Medical Center; and NeoRx, Seattle, WA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard","family":"Champlin","sequence":"additional","affiliation":[{"name":"From the MD Anderson Cancer Center, Houston, TX; 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