title: Dose-escalated radioimmunotherapy as part of reduced intensity conditioning for allogeneic transplantation in patients with advanced high-grade non-Hodgkin lymphoma.
abstract: A total of 20 patients enrolled in a multicenter phase II dose escalation study of radioimmunotherapy (RIT) using yttrium-90-ibritumomab tiuxetan at two dose levels (22 and 30 MBq/kg) in 10 patients, combined with reduced intensity conditioning (RIC) using fludarabine, melphalan and alemtuzumab followed by allogeneic hematopoietic cell transplantation (HCT) from either matched-related (n=5) or matched-unrelated donors (n=15). Postgrafting immunosuppression with cyclosporine was administered. Diagnoses were diffuse large B-cell lymphoma (n=13), transformed CLL (n=4), blastic mantle cell lymphoma (n=2) and follicular lymphoma grade 3 (n=1). Median age was 51 (range, 29-69) years. All patients were high risk with relapsed/refractory disease or relapse after preceding autologous HCT. Median follow-up of patients alive was 1115 (range, 1006-1252) days. No directly RIT-related toxicities were observed. The cumulative incidence of non-relapse mortality was 30%. Incidences of grade II-IV acute and chronic GvHD was 45% and 70%, respectively. Kaplan-Meier estimated 3-year OS and EFS were 20% for both dose levels. In conclusion, dose escalation of RIT and combined use with RIC is feasible with no additional toxicity due to dose escalation. This study is registered on http://clinicaltrials.gov as NCT00302757.
authors.affiliation: Department of Hematology and Oncology, Medical Center, University of Tuebingen, Tuebingen, Germany. wolfgang.bethge@med.uni-tuebingen.de
authors.forename: W A
authors.initials: WA
authors.lastname: Bethge
authors.forename: S
authors.initials: S
authors.lastname: von Harsdorf
authors.forename: M
authors.initials: M
authors.lastname: Bornhauser
authors.forename: B
authors.initials: B
authors.lastname: Federmann
authors.forename: M
authors.initials: M
authors.lastname: Stelljes
authors.forename: R
authors.initials: R
authors.lastname: Trenschel
authors.forename: H
authors.initials: H
authors.lastname: Baurmann
authors.forename: H
authors.initials: H
authors.lastname: Dittmann
authors.forename: C
authors.initials: C
authors.lastname: Faul
authors.forename: W
authors.initials: W
authors.lastname: Vogel
authors.forename: L
authors.initials: L
authors.lastname: Kanz
authors.forename: D
authors.initials: D
authors.lastname: Bunjes
mesh_terms: D000328:Adult; D000368:Aged; D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016572:Cyclosporine / Q000627:therapeutic use; D004307:Dose-Response Relationship, Radiation; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy / Q000532:radiotherapy* / Q000601:surgery; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D008875:Middle Aged; D060787:Neoplasm Grading; D011379:Prognosis; D011446:Prospective Studies; D016499:Radioimmunotherapy / Q000009:adverse effects / Q000379:methods*; D019275:Radiopharmaceuticals / Q000627:therapeutic use; D019172:Transplantation Conditioning / Q000009:adverse effects / Q000379:methods*; D014184:Transplantation, Homologous; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives; D015021:Yttrium Radioisotopes / Q000627:therapeutic use*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D019275:Radiopharmaceuticals; D015021:Yttrium Radioisotopes; D000074323:Alemtuzumab; C422802:ibritumomab tiuxetan; D016572:Cyclosporine; D014740:Vidarabine; C024352:fludarabine; D008558:Melphalan