title: Reduced-Intensity Conditioning Combined with (188)Rhenium Radioimmunotherapy before Allogeneic Hematopoietic Stem Cell Transplantation in Elderly Patients with Acute Myeloid Leukemia: The Role of In Vivo T Cell Depletion.
abstract: The combination of reduced-intensity conditioning, (188)rhenium anti-CD66 radioimmunotherapy, and in vivo T cell depletion was successfully applied in elderly patients with acute myeloid leukemia or myelodysplastic syndrome. Within a prospective phase II protocol, we investigated whether a dose reduction of alemtuzumab (from 75 mg to 50 mg MabCampath) would improve leukemia-free survival by reducing the incidence of relapse. Fifty-eight patients (median age, 67 years; range, 54 to 76) received radioimmunotherapy followed by fludarabine 150 mg/m(2) and busulfan 8 mg/kg combined with either 75 mg (n = 26) or 50 mg (n = 32) alemtuzumab. Although we observed a trend towards a shorter duration of neutropenia in the 50 mg group (median, 19 versus 21 days; P = .07), the time from transplantation to neutrophil and platelet engraftment as well as the overall incidence of engraftment did not differ. The incidence of severe acute graft-versus-host disease tended to be higher after the lower alemtuzumab dose (17% versus 4%; P = .15). No significant differences in the cumulative incidences of relapse (38% versus 35%; P = .81) or nonrelapse mortality (46% versus 27%; P = .31) were observed. Accordingly, disease-free and overall survival were not significantly different between groups. Although the feasibility of radioimmunotherapy plus reduced-intensity conditioning could be demonstrated in elderly patients, the dose reduction of alemtuzumab had no positive impact on overall outcome.
authors.affiliation: Department of Medicine I, University Hospital Carl Gustav Carus at Dresden University of Technology, Dresden, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Schneider
authors.affiliation: Department of Nuclear Medicine, University Hospital Carl Gustav Carus at Dresden University of Technology, Dresden, Germany.
authors.forename: Annette
authors.initials: A
authors.lastname: Strumpf
authors.affiliation: Department of Medicine I, University Hospital Carl Gustav Carus at Dresden University of Technology, Dresden, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Schetelig
authors.affiliation: Department of Nuclear Medicine, University Hospital Carl Gustav Carus at Dresden University of Technology, Dresden, Germany.
authors.forename: Gerd
authors.initials: G
authors.lastname: Wunderlich
authors.affiliation: Department of Medicine I, University Hospital Carl Gustav Carus at Dresden University of Technology, Dresden, Germany.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Ehninger
authors.affiliation: Department of Nuclear Medicine, University Hospital Carl Gustav Carus at Dresden University of Technology, Dresden, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Kotzerke
authors.affiliation: Department of Medicine I, University Hospital Carl Gustav Carus at Dresden University of Technology, Dresden, Germany; German Consortium for Translational Cancer Research, Dresden, Germany. Electronic address: martin.bornhaeuser@uniklinikum-dresden.de.
authors.forename: Martin
authors.initials: M
authors.lastname: Bornhäuser
mesh_terms: D000368:Aged; D000074323:Alemtuzumab; D064591:Allografts; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000627:therapeutic use*; D015703:Antigens, CD / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002066:Busulfan / Q000008:administration & dosage; D015815:Cell Adhesion Molecules / Q000276:immunology; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D005240:Feasibility Studies; D005260:Female; D006086:Graft vs Host Disease / Q000453:epidemiology / Q000209:etiology; D020544:Graft vs Leukemia Effect; D006801:Humans; D018796:Immunoconjugates / Q000627:therapeutic use*; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000532:radiotherapy / Q000628:therapy*; D008212:Lymphocyte Depletion / Q000009:adverse effects / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000188:drug therapy / Q000532:radiotherapy / Q000628:therapy*; D009503:Neutropenia / Q000209:etiology; D011446:Prospective Studies; D016499:Radioimmunotherapy; D011868:Radioisotopes / Q000627:therapeutic use*; D012211:Rhenium / Q000627:therapeutic use*; D013601:T-Lymphocytes / Q000276:immunology*; D019172:Transplantation Conditioning / Q000009:adverse effects / Q000379:methods*; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015703:Antigens, CD; D000951:Antigens, Neoplasm; C069847:CD66 antigens; D015815:Cell Adhesion Molecules; D018796:Immunoconjugates; D011868:Radioisotopes; D000074323:Alemtuzumab; D012211:Rhenium; D014740:Vidarabine; D002066:Busulfan; C024352:fludarabine
keywords: Acute myeloid leukemia; Alemtuzumab; Re-188 radioimmunotherapy; Reduced-intensity conditioning; Stem cell transplantation