Review Article

European Journal of Nuclear Medicine and Molecular Imaging

, Volume 36, Issue 3, pp 484-498

First online:

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

  • Inga BuchmannAffiliated withDepartment of Nuclear Medicine, University of HeidelbergUniversity of Lübeck Email author 
  • , Ralf G. MeyerAffiliated withDepartment of Medicine 3, University of Mainz
  • , Walter MierAffiliated withDepartment of Nuclear Medicine, University of Heidelberg
  • , Uwe HaberkornAffiliated withDepartment of Nuclear Medicine, University of HeidelbergUniversity of Lübeck

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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.

Keywords

Leukaemia Multiple myeloma Myeloablative conditioning Myeloablative radioimmunotherapy Stem cell transplantation