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High CD33-antigen loads in peripheral blood limit the efficacy of gemtuzumab ozogamicin (Mylotarg®) treatment in acute myeloid leukemia patients

Leukemia volume 18, pages 983–988 (2004)Cite this article

Abstract

Gemtuzumab ozogamicin (Mylotarg®) induces remission in approximately 30% of relapsed AML patients. We previously demonstrated that gemtuzumab infusion results in near-complete CD33 saturation in peripheral blood, and that saturating gemtuzumab levels result in continuous binding and internalization of gemtuzumab due to renewed CD33 expression. We now demonstrate that a high CD33-antigen load in peripheral blood is an independent adverse prognostic factor, likely due to peripheral consumption of gemtuzumab. Indeed, CD33 saturation in bone marrow is significantly reduced (40–90% saturation) as compared with CD33 saturation in corresponding peripheral blood samples (>90%). In vitro, such reduced CD33 saturation levels were strongly related with reduced cell kill. Apparently, high CD33-antigen loads in blood consume gemtuzumab and thereby limit its penetration into bone marrow. Consequently, CD33 saturation in bone marrow is reduced, which hampers efficient cell kill. Therefore, gemtuzumab should be administered at higher or repeated doses, or, preferably, after reduction of the leukemic cell burden by classical chemotherapy.

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Acknowledgements

We thank Marieke Comans-Bitter for preparation of the figures, Mark Berger, Mat Sherman, Cathy Eten, Gerry Messerschmidt, and Chantal Lejeune for support with the gemtuzumab protocols 0903B1-202-EU and 0903B1-203-EU, Philipp Hamann for helpful discussions, Dr WCJ Hop for help with statistical analyses, and Dr Ton Langerak, Dr Mirjam van der Burg, and Dr Jon Laman for critical reading of the manuscript.

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Authors and Affiliations

  1. Department of Immunology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands

    V H J van der Velden, J G te Marvelde, P G Hoogeveen & J J M van Dongen

  2. Department of Laboratory Medicine, Laboratory of Hematology, University Hospital Gasthuisberg, Leuven, Belgium

    N Boeckx

  3. Department of Hematology, LUMC, Leiden, The Netherlands

    I Jedema

  4. Department of Hematology, University Hospital Gasthuisberg, Leuven, Belgium

    M Boogaerts

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  1. V H J van der Velden
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van der Velden, V., Boeckx, N., Jedema, I. et al. High CD33-antigen loads in peripheral blood limit the efficacy of gemtuzumab ozogamicin (Mylotarg®) treatment in acute myeloid leukemia patients. Leukemia 18, 983–988 (2004). https://doi.org/10.1038/sj.leu.2403350

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