title: Dose-attenuated radioimmunotherapy with tositumomab and iodine 131 tositumomab in patients with recurrent non-Hodgkin's lymphoma (NHL) and extensive bone marrow involvement.
abstract: Radioimmunotherapy (RIT) with tositumomab and iodine 131 tositumomab can produce durable and complete responses in relapsed/refractory low-grade Non-Hodgkin's lymphoma. Patients with bone marrow involvement (BMI) with tumor >25% of the intertrabecular space are generally excluded from RIT because of risk of excessive hematologic toxicity. The authors conducted a dose-escalation study of tositumomab and iodine 131 tositumomab to determine whether RIT is feasible in this population. Patients had baseline BMI of >25% and platelet count of >or=150,000/mm3. In contrast to the usual 75 cGy total body dose of radiation, dose escalation of Iodine I 131 tositumomab began at a total body dose of 45 cGy, and increased to 55 cGy in a second cohort. Dose-limiting toxicity (DLT) was defined as absolute neutrophil count <500 cells/mm3 or platelets <25,000/mm3 for >17 days, or absolute neutrophil count <750/mm3 or platelets <50,000/mm3 for >24 days. Eleven subjects were enrolled (8 at 45 cGy and 3 at 55 cGy). Estimated BMI ranged from 30 to 65% (median approximately 40%). Patients had received a median of three prior chemotherapies (range 1 - 6). One of the six evaluable patients treated at 45 cGy experienced DLT. Three patients received 55 cGy, one had hematologic DLT concurrent with lymphoma progression and extensive BMI at relapse. Three of 11 (27%) patients received hematologic supportive care. Two patients had objective responses of 1 and 42.4+ months, respectively. RIT with attenuated dose iodine 131 tositumomab for patients with >25% BMI has acceptable toxicity and can result in lymphoma responses.
authors.affiliation: Center for Lymphoma and Myeloma, Division of Hematology/Oncology, Weill Medical College of Cornell University and New York Presbyterian Hospital, New York, NY 10021, USA.
authors.forename: Jodi V
authors.initials: JV
authors.lastname: Mones
authors.forename: Morton
authors.initials: M
authors.lastname: Coleman
authors.forename: Lale
authors.initials: L
authors.lastname: Kostakoglu
authors.forename: Richard R
authors.initials: RR
authors.lastname: Furman
authors.forename: Amy
authors.initials: A
authors.lastname: Chadburn
authors.forename: Tsiporah B
authors.initials: TB
authors.lastname: Shore
authors.forename: Daniel
authors.initials: D
authors.lastname: Muss
authors.forename: Patricia
authors.initials: P
authors.lastname: Stewart
authors.forename: Stewart
authors.initials: S
authors.lastname: Kroll
authors.forename: Shankar
authors.initials: S
authors.lastname: Vallabhajosula
authors.forename: Stanley J
authors.initials: SJ
authors.lastname: Goldsmith
authors.forename: John P
authors.initials: JP
authors.lastname: Leonard
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D018951:Antigens, CD20 / Q000276:immunology; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001853:Bone Marrow / Q000276:immunology*; D004307:Dose-Response Relationship, Radiation; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes; D016393:Lymphoma, B-Cell / Q000532:radiotherapy; D008224:Lymphoma, Follicular / Q000532:radiotherapy; D008228:Lymphoma, Non-Hodgkin / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000532:radiotherapy*; D016499:Radioimmunotherapy; D012074:Remission Induction
chemical_list: D000911:Antibodies, Monoclonal; D018951:Antigens, CD20; D000970:Antineoplastic Agents; D007457:Iodine Radioisotopes; C119496:tositumomab I-131