title: Assessment of treatment-related myelodysplastic syndromes and acute myeloid leukemia in patients with non-Hodgkin lymphoma treated with tositumomab and iodine I131 tositumomab.
abstract: The incidence of treatment-related myelodysplastic syndromes and acute myeloid leukemia (tMDSs/tAML) after tositumomab and iodine I(131) tositumomab administration to previously treated and untreated patients with non-Hodgkin lymphoma (NHL) was evaluated. A total of 1071 patients were enrolled in 7 studies: 995 with relapsed/refractory low-grade NHL, +/- transformation (median, 3 prior regimens [range, 1-13 regimens]) and 76 patients with previously untreated low-grade follicular NHL. A single dose of iodine tositumomab and I(131) tositumomab was administered. For tMDS/tAML patients, baseline and posttherapy peripheral blood and marrow specimens were reviewed in a blinded fashion. Median follow-up was 6 years from diagnosis and 2 years from radioimmunotherapy (RIT) for previously treated patients, and 4.6 years from radioimmunotherapy for previously untreated patients. tMDS/tAML was reported in 35 (3.5%) of 995 patients (annualized incidence, 1.6%/y [95% confidence interval, 1.0%-2.0%/y]), and 52% of the tMDS/tAML diagnoses of tMDS/tAML were confirmed in a blinded review (annualized incidence of 1.1%/y [95% confidence interval, 0.7%-1.6%/y]). Of the 25 cases, 10 patients (40%) were diagnosed with tMDS/tAML prior to receiving radioimmunotherapy; 2 (8%) had no pathologic or clinical evidence to support such a diagnosis; and 13 (52%) were confirmed to have developed tMDS/tAML following RIT. This incidence is consistent with that expected on the basis of patients' prior chemotherapy for NHL. With a median follow-up approaching 5 years, no case of tMDS/tAML has been reported in any of the 76 patients receiving iodine I(131) tositumomab as their initial therapy (P = .011 compared with previously treated patients).
authors.affiliation: James P. Wilmot Cancer Center, University of Rochester School of Medicine, Rochester, NY 14642, USA. john_bennett@urmc.rochester.edu <john_bennett@urmc.rochester.edu>
authors.forename: John M
authors.initials: JM
authors.lastname: Bennett
authors.forename: Mark S
authors.initials: MS
authors.lastname: Kaminski
authors.forename: John P
authors.initials: JP
authors.lastname: Leonard
authors.forename: Julie M
authors.initials: JM
authors.lastname: Vose
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Zelenetz
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Knox
authors.forename: Sandra
authors.initials: S
authors.lastname: Horning
authors.forename: Oliver W
authors.initials: OW
authors.lastname: Press
authors.forename: John A
authors.initials: JA
authors.lastname: Radford
authors.forename: Stewart M
authors.initials: SM
authors.lastname: Kroll
authors.forename: Robert L
authors.initials: RL
authors.lastname: Capizzi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects*; D002986:Clinical Trials as Topic; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D007457:Iodine Radioisotopes / Q000627:therapeutic use*; D015470:Leukemia, Myeloid, Acute / Q000139:chemically induced* / Q000175:diagnosis* / Q000453:epidemiology; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D009190:Myelodysplastic Syndromes / Q000139:chemically induced* / Q000175:diagnosis* / Q000453:epidemiology; D016499:Radioimmunotherapy / Q000009:adverse effects*; D011874:Radiometry; D012074:Remission Induction; D013997:Time Factors; D014916:Whole-Body Irradiation
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D007457:Iodine Radioisotopes; C119496:tositumomab I-131