Myeloablative doses of yttrium-90-ibritumomab tiuxetan and the risk of secondary myelodysplasia/acute myelogenous leukemia

Cancer. 2011 Nov 15;117(22):5074-84. doi: 10.1002/cncr.26182. Epub 2011 May 12.

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.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal / adverse effects*
  • Antibodies, Monoclonal / therapeutic use
  • Bone Marrow / drug effects
  • Bone Marrow / pathology
  • Bone Marrow / radiation effects
  • Female
  • Follow-Up Studies
  • Granulocyte-Macrophage Progenitor Cells / cytology
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / drug effects
  • Hematopoietic Stem Cells / radiation effects
  • Humans
  • Leukemia, Myeloid, Acute / etiology*
  • Lymphoma, Non-Hodgkin / drug therapy
  • Lymphoma, Non-Hodgkin / radiotherapy
  • Male
  • Middle Aged
  • Myelodysplastic Syndromes / etiology*
  • Neoplasms, Second Primary / etiology*
  • Radioimmunotherapy / adverse effects*
  • Risk
  • Telomere / drug effects
  • Telomere / radiation effects
  • Yttrium Radioisotopes / adverse effects*
  • Yttrium Radioisotopes / therapeutic use

Substances

  • Antibodies, Monoclonal
  • Yttrium Radioisotopes
  • ibritumomab tiuxetan