title: Myeloablative radioimmunotherapy in conditioning prior to haematological stem cell transplantation: closing the gap between benefit and toxicity?
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 beta-emitter (90)Y 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.
authors.affiliation: Department of Nuclear Medicine, University of Heidelberg, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany. Inga.buchmann@uk-sh.de
authors.forename: Inga
authors.initials: I
authors.lastname: Buchmann
authors.forename: Ralf G
authors.initials: RG
authors.lastname: Meyer
authors.forename: Walter
authors.initials: W
authors.lastname: Mier
authors.forename: Uwe
authors.initials: U
authors.lastname: Haberkorn
mesh_terms: D002986:Clinical Trials as Topic; D003131:Combined Modality Therapy; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D006801:Humans; D018796:Immunoconjugates / Q000009:adverse effects / Q000627:therapeutic use; D007938:Leukemia / Q000628:therapy; D009101:Multiple Myeloma / Q000628:therapy; D019653:Myeloablative Agonists / Q000009:adverse effects / Q000627:therapeutic use*; D009436:Neural Tube Defects / Q000628:therapy; D016499:Radioimmunotherapy / Q000009:adverse effects / Q000379:methods*; D011879:Radiotherapy Dosage; D019172:Transplantation Conditioning / Q000009:adverse effects / Q000379:methods*
chemical_list: D018796:Immunoconjugates; D019653:Myeloablative Agonists