title: Myeloablative anti-CD20 radioimmunotherapy +/- high-dose chemotherapy followed by autologous stem cell support for relapsed/refractory B-cell lymphoma results in excellent long-term survival.
abstract: BACKGROUND
  Radioimmunotherapy (RIT) has been used to treat relapsed/refractory CD20+ Non-Hodgkin lymphoma (NHL). Myeloablative anti-CD20 RIT followed by autologous stem cell infusion (ASCT) enables high radiation doses to lymphoma sites. We performed a phase I/II trial to assess feasibility and survival.
  
  
  METHODS
  Twenty-three patients with relapsed/refractory NHL without complete remission (CR) to salvage chemotherapy were enrolled to evaluate RIT with Iodine-131 labelled rituximab (131I-rituximab) in a myeloablative setting. Biodistribution and dosimetric studies were performed to determine 131I activity required to induce a total body dose of 21-27Gy to critical organs. In 6/23 patients RIT was combined with high-dose chemotherapy. 8/23 patients received a sequential high-dose chemotherapy with a second ASCT. The median follow-up is 9.5 years.
  
  
  RESULTS
  6.956-19.425GBq of 131I was delivered to achieve the limiting organ dose to lungs or kidneys. No grade III/IV non-hematologic toxicity was seen with RIT alone. Significant grade III/IV toxicity (mucositis, fever, infection, one therapy related death) was observed in patients treated with RIT combined with high-dose chemotherapy. The overall response rate was 87% (64% CR). The median progression-free (PFS) and overall survival (OS) is 47.5 and 101.5 months. An international prognostic index score >1 was predictive for OS.
  
  
  CONCLUSIONS
  Myeloablative RIT with 131I-rituximab followed by ASCT is feasible, well-tolerated and effective in high risk CD20+ NHL. Combination of RIT and high-dose chemotherapy increased toxicity significantly. Long-term results for PFS and OS are encouraging.
authors.affiliation: III. Medical Department, Technische Universität München, Munich, Germany.
authors.forename: Julia Y
authors.initials: JY
authors.lastname: Wagner
authors.forename: Kathleen
authors.initials: K
authors.lastname: Schwarz
authors.forename: Susanne
authors.initials: S
authors.lastname: Schreiber
authors.forename: Burkhard
authors.initials: B
authors.lastname: Schmidt
authors.forename: Hans-Jürgen
authors.initials: HJ
authors.lastname: Wester
authors.forename: Markus
authors.initials: M
authors.lastname: Schwaiger
authors.forename: Christian
authors.initials: C
authors.lastname: Peschel
authors.forename: Christoph
authors.initials: C
authors.lastname: von Schilling
authors.forename: Klemens
authors.initials: K
authors.lastname: Scheidhauer
authors.forename: Ulrich
authors.initials: U
authors.lastname: Keller
mesh_terms: D000328:Adult; D000368:Aged; D058846:Antibodies, Monoclonal, Murine-Derived; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes / Q000008:administration & dosage; D016393:Lymphoma, B-Cell / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000628:therapy; D036102:Peripheral Blood Stem Cell Transplantation / Q000379:methods; D016499:Radioimmunotherapy / Q000379:methods*; D019275:Radiopharmaceuticals / Q000008:administration & dosage; D012307:Risk Factors; D000069283:Rituximab; D016019:Survival Analysis; D014182:Transplantation, Autologous / Q000379:methods
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D007457:Iodine Radioisotopes; D019275:Radiopharmaceuticals; D000069283:Rituximab