title: Myeloablative I-131-tositumomab with escalating doses of fludarabine and autologous hematopoietic transplantation for adults age ≥ 60 years with B cell lymphoma.
abstract: Myeloablative therapy and autologous stem cell transplantation (ASCT) are underutilized in older patients with B cell non-Hodgkin (B-NHL) lymphoma. We hypothesized that myeloablative doses of (131)I-tositumomab could be augmented by concurrent fludarabine, based on preclinical data indicating synergy. Patients were ≥ 60 years of age and had high-risk, relapsed, or refractory B-NHL. Therapeutic infusions of (131)I-tositumomab were derived from individualized organ-specific absorbed dose estimates delivering ≤ 27 Gy to critical organs. Fludarabine was initiated 72 hours later followed by ASCT to define the maximally tolerated dose. Thirty-six patients with a median age of 65 years (range, 60 to 76), 2 (range, 1 to 9) prior regimens, and 33% with chemoresistant disease were treated on this trial. Dose-limiting organs included lung (30), kidney (4), and liver (2) with a median administered (131)I activity of 471 mCi (range, 260 to 1620). Fludarabine was safely escalated to 30 mg/m(2) × 7 days. Engraftment was prompt, there were no early treatment-related deaths, and 2 patients had ≥ grade 4 nonhematologic toxicities. The estimated 3-year overall survival, progression-free survival, and nonrelapse mortality were 54%, 53%, and 7%, respectively (median follow up of 3.9 years). Fludarabine up to 210 mg/m(2) can be safely delivered with myeloablative (131)I-tositumomab and ASCT in older adults with B-NHL.
authors: Division of Medical Oncology, Department of Medicine, University of Washington, Seattle, Washington; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington. Electronic address: agopal@u.washington.edu.
authors: Ajay K
authors: AK
authors: Gopal
authors: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors: Ted A
authors: TA
authors: Gooley
authors: Division of Nuclear Medicine, Department of Radiology, University of Washington, Seattle, Washington.
authors: Joseph G
authors: JG
authors: Rajendran
authors: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors: John M
authors: JM
authors: Pagel
authors: Pacific Northwest National Laboratory, Richland, Washington.
authors: Darrell R
authors: DR
authors: Fisher
authors: Division of Medical Oncology, Department of Medicine, University of Washington, Seattle, Washington; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors: David G
authors: DG
authors: Maloney
authors: Division of Medical Oncology, Department of Medicine, University of Washington, Seattle, Washington; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors: Frederick R
authors: FR
authors: Appelbaum
authors: Division of Medical Oncology, Department of Medicine, University of Washington, Seattle, Washington; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors: Ryan D
authors: RD
authors: Cassaday
authors: Division of Nuclear Medicine, Department of Radiology, University of Washington, Seattle, Washington.
authors: Andrew
authors: A
authors: Shields
authors: Division of Medical Oncology, Department of Medicine, University of Washington, Seattle, Washington; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors: Oliver W
authors: OW
authors: Press
mesh_terms: D000367:Age Factors; D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D059248:Chemoradiotherapy; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D007457:Iodine Radioisotopes / Q000008:administration & dosage* / Q000493:pharmacokinetics; D016393:Lymphoma, B-Cell / Q000188:drug therapy / Q000532:radiotherapy / Q000628:therapy*; D020522:Lymphoma, Mantle-Cell / Q000188:drug therapy / Q000532:radiotherapy / Q000628:therapy; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016499:Radioimmunotherapy; D019275:Radiopharmaceuticals / Q000627:therapeutic use; D014182:Transplantation, Autologous; D014740:Vidarabine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D000911:Antibodies, Monoclonal; D007457:Iodine Radioisotopes; D019275:Radiopharmaceuticals; D014740:Vidarabine; C119496:tositumomab I-131; C024352:fludarabine
keywords: Autologous; B cell lymphoma; Elderly; Radioimmunotherapy