title: Myeloablative doses of yttrium-90-ibritumomab tiuxetan and the risk of secondary myelodysplasia/acute myelogenous leukemia.
abstract: BACKGROUND
  Because the long-term toxicity of myeloablative radioimmunotherapy remains a matter of concern, the authors evaluated the hematopoietic damage and incidence of secondary myelodysplastic syndrome and acute myelogenous leukemia (sMDS/AML) in patients who received myeloablative doses of the radiolabeled antibody yttrium-90 (⁹⁰Y)-ibritumomab tiuxetan.
  
  
  METHODS
  The occurrence of sMDS/AML was investigated prospectively in 53 elderly patients with non-Hodgkin lymphoma (NHL) who underwent an autograft after high-dose radioimmunotherapy (HD-RIT) myeloablative conditioning with ⁹⁰Y-ibritumomab tiuxetan. Bone marrow (BM) hematopoietic progenitors and telomere length (TL) also were investigated.
  
  
  RESULTS
  At a median follow-up of 49 months, 4 patients developed sMDS/AML at 6 months, 12 months, 27 months, and 36 months after HD-RIT, and the 5-year cumulative incidence of sMDS/AML was 8.29%. A significant but transient decrease in BM granulocyte-macrophage progenitors was observed; whereas multilineage, erythroid, and fibroblast progenitors were unaffected. A significant and persistent shortening of BM TL also was detected. A matched-pair analysis comparing the study patients with 55 NHL patients who underwent autografts after chemotherapy-based myeloablative conditioning demonstrated a 8.05% 5-year cumulative incidence of sMDS/AML.
  
  
  CONCLUSIONS
  HD-RIT for patients with NHL was associated with 1) limited toxicity on hematopoietic progenitors, 2) accelerated TL shortening, and 3) non-negligible incidence of sMDS/AML, which nevertheless was comparable to the incidence observed in a matched group of patients who received chemotherapy-based conditioning. Thus, in the current series of elderly patients with NHL, the development of sMDS/AML was not influenced substantially by HD-RIT.
authors.affiliation: Medical Oncology 3, National Cancer Institute, Milan, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Guidetti
authors.forename: Carmelo
authors.initials: C
authors.lastname: Carlo-Stella
authors.forename: Marco
authors.initials: M
authors.lastname: Ruella
authors.forename: Rosalba
authors.initials: R
authors.lastname: Miceli
authors.forename: Lilli
authors.initials: L
authors.lastname: Devizzi
authors.forename: Silvia L
authors.initials: SL
authors.lastname: Locatelli
authors.forename: Arianna
authors.initials: A
authors.lastname: Giacomini
authors.forename: Adele
authors.initials: A
authors.lastname: Testi
authors.forename: Stefano
authors.initials: S
authors.lastname: Buttiglieri
authors.forename: Alessandra
authors.initials: A
authors.lastname: Risso
authors.forename: Luigi
authors.initials: L
authors.lastname: Mariani
authors.forename: Massimo
authors.initials: M
authors.lastname: Di Nicola
authors.forename: Roberto
authors.initials: R
authors.lastname: Passera
authors.forename: Corrado
authors.initials: C
authors.lastname: Tarella
authors.forename: Alessandro M
authors.initials: AM
authors.lastname: Gianni
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects* / Q000627:therapeutic use; D001853:Bone Marrow / Q000187:drug effects / Q000473:pathology / Q000528:radiation effects; D005260:Female; D005500:Follow-Up Studies; D055014:Granulocyte-Macrophage Progenitor Cells / Q000166:cytology; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000209:etiology*; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy / Q000532:radiotherapy; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000209:etiology*; D016609:Neoplasms, Second Primary / Q000209:etiology*; D016499:Radioimmunotherapy / Q000009:adverse effects*; D012306:Risk; D016615:Telomere / Q000187:drug effects / Q000528:radiation effects; D015021:Yttrium Radioisotopes / Q000009:adverse effects* / Q000627:therapeutic use
chemical_list: D000911:Antibodies, Monoclonal; D015021:Yttrium Radioisotopes; C422802:ibritumomab tiuxetan