High-dose chemoradiotherapy with allogeneic bone marrow or peripheral blood stem cell transplantation (SCT) is a potentially curative treatment for advanced or poor-prognosis hematological malignancies. This procedure was initially considered as a means to deliver supralethal doses of chemotherapy and radiation for the eradication of the malignancy, but it has subsequently become apparent that much of the therapeutic benefit of SCT relates to an associated immune-mediated graft-versus-leukemia (GVL) effect. Additionally, due to the increased risk of morbidity and graft-versus-host disease (GVHD) that occurs with advanced age, the use of standard myeloablative preparative regimens with allogeneic progenitor cell transplantation has been generally limited to younger patients in good medical condition. However, most patients with hematologic malignancies are older and therefore the overall impact of allografting is relatively small. Thus despite resulting in high rates of long term disease control, allografting is only performed in a small fraction of patients, either because of lack of a suitable donor or the high risk of toxicity due to age or the general medical condition. Therefore strategies aimed at improving the safety and tolerability of allografting to allow for its more frequent application in older patients are necessary.
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