Efficient bone marrow irradiation and low uptake by non-haematological organs with an yttrium-90-anti-CD66 antibody prior to haematopoietic stem cell transplantation

Abstract

We report the results of a Phase I radiation dose escalation study using an yttrium-90 (⁹⁰Y) labelled anti-CD66 monoclonal antibody given with standard conditioning regimen for patients receiving haematopoietic stem cell transplants for myeloid leukaemia or myeloma. The ⁹⁰Y-labelled anti-CD66 was infused prior to standard conditioning. In total, 30 patients entered the trial and 29 received ⁹⁰Y-labelled mAb, at infused radiation activity levels of 5, 10, 25, or 37.5 megaBequerel (MBq)/kg lean body weight. A prerequisite for receiving the ⁹⁰Y-labelled mAb was favourable dosimetry determined by single-photon emission computerised tomography (SPECT) dosimetry following administration of indium-111 (¹¹¹In) anti-CD66. Estimated absorbed radiation doses delivered to the red marrow demonstrated a linear relationship with the infused activity of ⁹⁰Y-labelled mAb. At the highest activity level of 37.5 MBq/kg, mean estimated radiation doses for red marrow, liver, spleen, kidneys and lungs were 24.6 ± 5.6 Gy, 5.8 ± 2.7 Gy, 19.1 ± 8.0 Gy, 2.1 ± 1.1 and 2.2 ± 0.9, respectively. All patients engrafted, treatment-related mortality 1-year post-transplant was zero. Toxicities were no greater than those anticipated for similar conditioning regimens without targeted radiation. The ability to substantially intensify conditioning prior to haematopoietic stem cell transplantation without increasing toxicity warrants further testing to determine efficacy. clinicaltrials.gov identifier: NCT01521611.

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