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Myeloablative radioimmunotherapy in conditioning prior to haematological stem cell transplantation: closing the gap between benefit and toxicity?

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Abstract

High-dose radio-/chemotherapy in the context of autologous and allogeneic haematopoietic stem cell transplantation is a double-edged sword. The requirement for dose intensification is linked to an increase in toxicity to noninvolved organs. Particularly for older patients and patients with comorbidities, efficient but toxicity-reduced schemes are needed. Myeloablative radioimmunotherapy is a targeted, internal radiotherapy that uses radiolabelled monoclonal antibodies (mAb) with affinity to the bone marrow. It involves the administration of high radiation doses (up to 30 Gy) to the bone marrow and spleen but without exposing radiosensitive organs to doses higher than 1–7 Gy. Added to conventional or intensity-reduced conditioning, myeloablative radioimmunotherapy may achieve a pronounced antileukaemic effect with tolerable toxicities. A rational and individual design of the ideal nuclide–antibody combination optimizes therapy. The anti-CD33, anti-CD45 and anti-CD66 mAbs appear to be ideal tracers so far. The β-emitter 90Y is coupled by DTPA and is the best nuclide for myeloablation. Approval trials for DTPA anti-CD66 mAb are underway in Europe, and in the near future these therapies may become applicable in practice. This review gives an overview of current myeloablative conditioning radioimmunotherapy. We discuss the selection of the optimal radioimmunoconjugate and discuss how radioimmunotherapy might be optimized in the future by individualization of therapy protocols. We also highlight the potential advantages of combination therapies.

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Acknowledgments

We thank colleagues of the Department of Nuclear Medicine and the Department of Hematology of the University Hospitals of Heidelberg, Mainz and Ulm, Germany, who have supported the establishment of myeloablative radioimmunotherapy and have contributed to the care of our patients.

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Authors and Affiliations

  1. Department of Nuclear Medicine, University of Heidelberg, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany

    Inga Buchmann, Walter Mier & Uwe Haberkorn

  2. Department of Medicine 3, University of Mainz, Mainz, Germany

    Ralf G. Meyer

  3. University of Lübeck, Ratzebürger Allee 160, 23538, Lübeck, Germany

    Inga Buchmann & Uwe Haberkorn

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  1. Inga Buchmann
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Correspondence to Inga Buchmann.

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Buchmann, I., Meyer, R.G., Mier, W. et al. Myeloablative radioimmunotherapy in conditioning prior to haematological stem cell transplantation: closing the gap between benefit and toxicity?. Eur J Nucl Med Mol Imaging 36, 484–498 (2009). https://doi.org/10.1007/s00259-008-0996-6

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  • DOI: https://doi.org/10.1007/s00259-008-0996-6

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