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European Journal of Nuclear Medicine and Molecular Imaging

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01.11.2009 | Original Article

Absorbed dose and biologically effective dose in patients with high-risk non-Hodgkin’s lymphoma treated with high-activity myeloablative ⁹⁰Y-ibritumomab tiuxetan (Zevalin®)

verfasst von: C. Chiesa, F. Botta, A. Coliva, M. Maccauro, L. Devizzi, A. Guidetti, C. Carlo-Stella, E. Seregni, M. A. Gianni, E. Bombardieri

Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging | Ausgabe 11/2009

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Abstract

Purpose

The aim of this study was to carry out two different dose estimation approaches in patients with non-Hodgkin’s lymphoma (NHL) treated with a myeloablative amount of ⁹⁰Y-labelled ibritumomab tiuxetan (Zevalin®) in an open-label dose escalation study.

Methods

Twenty-seven patients with relapsed/refractory or de novo high-risk NHL receiving one myeloablative dose of ⁹⁰Y-ibritumomab tiuxetan followed by tandem stem cell reinfusion were evaluated for dose estimate. The injected activity was 30 MBq/kg in 12 patients and 45 MBq/kg in 15 patients. Dose estimation was performed 1 week prior to ⁹⁰Y-ibritumomab tiuxetan by injection of ¹¹¹In-ibritumomab tiuxetan (median activity: 200 MBq). The absorbed dose (D) and the biologically effective dose (BED) were calculated.

Results

The absorbed doses per unit activity (Gy/GBq) were [median (range)]: heart wall 4.6 (2.5–9.7), kidneys 5.1 (2.8–10.5), liver 6.1 (3.9–10.4), lungs 2.9 (1.5–6.8), red marrow 1.0 (0.5–1.7), spleen 7.0 (1.5–14.4) and testes 4.9 (2.9–16.7). The absorbed dose (Gy) for the 15 patients treated with 45 MBq/kg were: heart wall 17.0 (8.7–25.4), kidneys 17.1 (7.9–22.4), liver 20.8 (15.4–28.3), lungs 8.1 (5.4–11.4), red marrow 3.1 (2.0–4.0), spleen 26.2 (17.0–35.6) and testes 17.3 (9.0–28.4). At the highest activities the acute haematological toxicity was mild or moderate and of very short duration, and it was independent of the red marrow absorbed dose. No secondary malignancy or treatment-related myelodysplastic syndrome was observed. No non-haematological toxicity (liver, kidney, lung) was observed during a follow-up period of 24–48 months.

Conclusion

The use of 45 MBq/kg of ⁹⁰Y-ibritumomab tiuxetan in association with stem cell autografting resulted in patients being free of toxicity in non-haematological organs. These clinical findings were in complete agreement with our dose estimations, considering both organ doses and BED values.

After completion of this dosimetric study, 57 patients were treated with 45 MBq/kg in an ongoing clinical study without dose estimation, for a total of 72 treatments with 45 MBq/kg.

After completion of this dosimetric study, a total of 72 patients were treated with 45 MBq/kg and no extrahaematological toxicity was observed.

In our limited experience with an anti-α-folate receptor immunoconjugate developed in our Institute (90Y-Mov18) for the treatment of ovarian cancer, we observed a similar mismatch between low blood-based red marrow dose and high haematological toxicity in the presence of visible spine.

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Titel: Absorbed dose and biologically effective dose in patients with high-risk non-Hodgkin’s lymphoma treated with high-activity myeloablative 90Y-ibritumomab tiuxetan (Zevalin®)
verfasst von: C. Chiesa
F. Botta
A. Coliva
M. Maccauro
L. Devizzi
A. Guidetti
C. Carlo-Stella
E. Seregni
M. A. Gianni
E. Bombardieri
Publikationsdatum: 01.11.2009
Verlag: Springer-Verlag
Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging / Ausgabe 11/2009
Print ISSN: 1619-7070
Elektronische ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-009-1141-x

Springer Medizin

Abstract

Purpose

Methods

Results

Conclusion

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