title: 188Re anti-CD66 radioimmunotherapy combined with reduced-intensity conditioning and in-vivo T cell depletion in elderly patients undergoing allogeneic haematopoietic cell transplantation.
abstract: The addition of radioimmunotherapy to conventional and reduced-intensity conditioning has been shown to be feasible and effective. Within an ongoing prospective phase II trial, 22 patients with advanced myeloid malignancies and a median age of 65 years (range 54-76) received anti-CD66 Rhenium radioimmunotherapy followed by fludarabine (150 mg/m(2)), busulfan (8 mg/kg) and alemtuzumab (75 mg) before allogeneic haematopoietic stem cell transplantation from matched sibling (n = 7) and unrelated donors (n = 15). The extramedullary toxicity in the first 100 d post-transplantation was limited and all patients engrafted with complete donor chimaerism. The incidence of non-relapse mortality at day 100 and after 2 years was 4.5% and 23%, respectively. The probability of overall survival at 2 years was 40%. A comparison with a younger historical cohort (median age 57 years) having received the same dose of fludarabine and busulfan but neither radioimmunotherapy nor alemtuzumab showed no difference in outcome. Although the use of alemtuzumab reduced the incidence of acute graft-versus-host-disease, it was associated with a relapse incidence of 40% despite the incorporation of radioimmmunotherapy. In summary, we confirmed the feasibility of combined radioimmunotherapy and reduced-intensity conditioning in elderly patients. Further optimisation, probably involving less T cell depletion, is necessary before a randomized comparison with standard conditioning can be planned.
authors.affiliation: Medizinische Klinik und Poliklinik I, University Hospital Carl Gustav Carus, Fetscherstrasse 74, Dresden, Germany.
authors.forename: Anett
authors.initials: A
authors.lastname: Lauter
authors.forename: Annette
authors.initials: A
authors.lastname: Strumpf
authors.forename: Uwe
authors.initials: U
authors.lastname: Platzbecker
authors.forename: Johannes
authors.initials: J
authors.lastname: Schetelig
authors.forename: Martin
authors.initials: M
authors.lastname: Wermke
authors.forename: Jörgen
authors.initials: J
authors.lastname: Radke
authors.forename: Alexander
authors.initials: A
authors.lastname: Kiani
authors.forename: Gerd
authors.initials: G
authors.lastname: Wunderlich
authors.forename: Christian
authors.initials: C
authors.lastname: Thiede
authors.forename: Gerhard
authors.initials: G
authors.lastname: Ehninger
authors.forename: Jorg
authors.initials: J
authors.lastname: Kotzerke
authors.forename: Martin
authors.initials: M
authors.lastname: Bornhäuser
mesh_terms: D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000276:immunology; D004812:Epidemiologic Methods; D017707:Erythrocyte Transfusion; D005260:Female; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000209:etiology; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000532:radiotherapy*; D008212:Lymphocyte Depletion / Q000379:methods; D008297:Male; D008875:Middle Aged; D017713:Platelet Transfusion; D016499:Radioimmunotherapy / Q000009:adverse effects / Q000379:methods*; D011868:Radioisotopes / Q000627:therapeutic use; D012008:Recurrence; D012211:Rhenium / Q000627:therapeutic use*; D019172:Transplantation Conditioning / Q000379:methods*
chemical_list: D015703:Antigens, CD; D000951:Antigens, Neoplasm; C069847:CD66 antigens; D015815:Cell Adhesion Molecules; D011868:Radioisotopes; D012211:Rhenium