Adult acute leukemia: a need for continued translational research.

Over the past 2 to 3 decades, the outlook for diverse types of acute leukemias has changed from rapidly fatal to potentially curable diseases. This gratifying change is mainly applicable to childhood acute lymphocytic leukemia (ALL) patients, where more than 70% enjoy greater than 5-year survival, but also holds true for some adults (in particular those under the age of 60) with acute myelogenous leukemia (AML) and ALL. However, even in the younger adult population, only about 30% are able to attain such long-term survival. Unfortunately, that degree of improvement has yet to be realized for older adults, those with therapy-induced (secondary) leuke-mias, or those whose leukemias have evolved from myelodysplastic syndrome (MDS). Thus, the leukemias continue to present a formidable challenge for which there is not yet a reliably curative standard approach for the majority of adults with this family of diseases. In this respect, clinical investigation-the design, implementation, and analysis of new strategies aimed at increasing the cure rate is necessary to provide state-of-the-art treatment and medical care in addition to measuring the efficacy of new approaches and validation of their widespread applications. Most adult patients with newly diagnosed acute leukemia are able to achieve a complete remission (CR) in response to induction chemotherapy. Although the most appropriate form of potentially curative postremission therapy continues to be controversial, the long-term clinical results of both bone marrow transplantation (BMT) and dose-intensive chemotherapy in first CR continue to improve for several leukemia patient subgroups. The advances achieved to date in disease-free survival (DFS) are, in large part, attributable to the design and implementation of intensive cytoreduc-tive therapies which, in turn, have been made possible only by aggressive support measures. There is no question that, in addition to increasing the DFS rate in these patient populations, intensive cyto-toxic therapy is accompanied by a heightened risk for widespread mucosal and nonhematopoietic multi-organ toxicities as well as profound marrow aplasia. With an increasing ability to manage and in some instances circumvent diverse cytotoxic complications, the full antileukemic potential of aggressive cytoreductive therapy can be evaluated. Thus, patients receiving high-dose ara-C therapy in first CR have achieved a prolongation of DFS and cure compared with those patients receiving less intensive regimens. In addition, mye-loablative therapy followed by either autologous or allogeneic BMT also results in substantial cure rates in patients able to tolerate this more aggressive approach. Yet, despite this progress, aggressive cytoreductive therapy …