Radioimmunoconjugates in acute leukemia treatment: the future is radiant.
Targeted radiotherapy of the bone marrow using radiolabeled monoclonal antibodies is a therapeutic approach of considerable potential for the treatment of acute leukemia in addition to or as a substitute for total body irradiation. The data currently available, of about 300 patients, suggest that radioimmunotherapy (RIT) with beta-emitters in acute leukemia is feasible and safe using a variety of antibodies (anti-CD33, anti-CD45, anti-CD66) and radionuclides (131I, 90Y, 188Re). It appears to reduce the risk of relapse in high-risk acute myelogenous leukemia (AML) patients transplanted early in the course of their disease (<15% blasts) to 20-30%. Furthermore, it has shown the potential to safely intensify reduced-intensity conditioning regimens (nonrelapse mortality of 25% compared to relapse rate of 55% within 2 years). Significant improvements in the results of refractory patients will probably depend on the successful further development of RIT with alpha-emitters or the use of a cocktail of antibodies labeled with alpha- and beta-emitters, in a first dose escalation study of 213Bi-labeled anti-CD33 in refractory AML (partial) remission could be achieved in 5/18 patients. Randomized trials to evaluate the therapeutic efficacy of RIT in the context of stem cell transplantation have been initiated and the results are keenly anticipated.
Kotzerke
J
J
Klinik und Poliklinik für Nuklearmedizin, Universitätsklinikum Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany. joerg.kotzerke@mailbox.tu-dresden.de
Bunjes
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Scheinberg
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D000512:Alpha Particles; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD / Q000096:biosynthesis; D015214:Antigens, Differentiation, Myelomonocytic / Q000096:biosynthesis; D001610:Beta Particles; D015815:Cell Adhesion Molecules / Q000096:biosynthesis; D002986:Clinical Trials as Topic; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D018796:Immunoconjugates / Q000627:therapeutic use*; D007938:Leukemia / Q000532:radiotherapy*; D017493:Leukocyte Common Antigens / Q000096:biosynthesis; D011786:Quality Control; D016499:Radioimmunotherapy; D011868:Radioisotopes / Q000627:therapeutic use; D011874:Radiometry; D012211:Rhenium / Q000627:therapeutic use; D063268:Sialic Acid Binding Ig-like Lectin 3; D033581:Stem Cell Transplantation; D015021:Yttrium Radioisotopes / Q000627:therapeutic use
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; C571163:CD33 protein, human; C069847:CD66 antigens; D015815:Cell Adhesion Molecules; D018796:Immunoconjugates; D011868:Radioisotopes; D063268:Sialic Acid Binding Ig-like Lectin 3; D015021:Yttrium Radioisotopes; D012211:Rhenium; D017493:Leukocyte Common Antigens