Targeted Radiotherapy As An Adjunct To Hematopoietic Stem Cell Transplantation For Advanced Leukemia

Currently, hematopoietic stem cell transplantation (HSCT) offers the highest chance of cure for most patients with acute leukemia or chronic myelogenous leukemia (CML) beyond chronic phase. Conditioning regimens consisting of highdose chemotherapy with or without total body irradiation (TBI) followed by HLA-matched related-donor HSCT offer long-term, disease-free survival rates of 45% to 65% for patients with acute myeloid leukemia (AML) transplanted in first complete remission (CR), and 30% for AML patients transplanted with refractory or relapsed disease.1 However, both rates of disease relapse and transplant-related mortality remain unacceptably high following HSCT using conventional chemotherapyand TBI-containing conditioning regimens, and clinical trials examining increased-intensity conditioning regimens as a means of reducing the risk of relapse have almost uniformly demonstrated increased transplant-related mortality.2–4 Targeted radiotherapy delivered by radioimmunoconjugates has evolved as a means of selectively directing radiation to leukemic cells and/or surrounding normal hematopoietic cells while relatively sparing radiation-sensitive, non-hematopoietic tissues such as liver, lung, and mucous membranes. Theoretically, such an approach would serve to decrease both relapse rates and transplant-related toxicity and mortality, particularly if targeted radiation could be used in place of, rather than in addition to, TBI. There are three major “components” of radioimmunoconjugates that directly affect how well they are able to deliver radiation selectively to target tissues: the antigen against which the antibody is directed, the structure of the antibody itself, and the radioisotope. Each of these components may be modified, albeit with varying degrees of difficulty, in order to improve targeting and tolerability of radioimmunotherapy (RIT). Through modification of the various components of previously studied radioimmunoconjugates, the field of RIT for the treatment of leukemia continues to evolve, and the work reported by Buchmann et al in this issue is indicative of this ongoing evolution.