Hematology 2009 385 Independent prognostic factors for AML outcome David Grimwade 1 and Robert K. Hills 2 1 Department of Medical & Molecular Genetics, King’s College London School of Medicine, London, United Kingdom; 2 Department of Haematology, School of Medicine, Cardiff University, Cardiff, United Kingdom Over the last three decades there have been dramatic advances in deciphering the cytogenetic and molecular lesions underlying the pathogenesis of acute myeloid leukemia (AML). These have not only afforded greater insights into disease biology, but also provided useful information predicting the likeli- hood of any given patient achieving and maintaining remission following conventional chemotherapy, leading to the development of risk-stratified treatment approaches. However, it is becoming increasingly apparent that AML is highly heterogeneous at the molecular level. Defining the individual genetic abnor- malities or combinations of markers that provide significant independent prognostic information and establishing their respective relationships to other pre-treatment characteristics that impact on outcome, such as age and presenting white blood cell count, presents a major ongoing challenge. Moreover, there is increasing evidence that risk of relapse and overall survival can be predicted by assessment of kinetics and depth of response following front-line therapy and monitoring of the leukemic burden using molecu- lar or immunological approaches to minimal residual disease (MRD) detection. These advances present the exciting prospect that panels of pre-treatment parameters affording independent prognostic informa- tion can be integrated with precise measurement of treatment response using MRD technologies to provide greater refinement in risk-adapted management of AML. This could lead to further improvements in outcome and serve to identify in a more reliable fashion those patients most likely to benefit from allogeneic transplant in first remission. C urrent management of patients with acute myeloid leukemia (AML) is determined by a number of parameters, including age, performance status and the cytogenetic/molecular genetic characteristics of the leukemic clone. Together, these factors have an important bearing on treatment strategy, identifying potential candidates for molecularly targeted therapies (eg, all trans retinoic acid [ATRA] and arsenic trioxide in PML-RARA + acute promyelocytic leukemia, or FLT3 inhibitors in AML with FLT3 mutations) and informing decisions on alloge- neic transplantation. In older adults (defined as older than 60 years) presenting with AML, who account for the majority with the disease and who generally have a poor prognosis, the major goal of pre-treatment assessment is to distinguish those patients who may benefit from intensive chemotherapy. Rapid cytogenetic analysis can be particularly helpful, identifying patients with AML with adverse karyotypic features, who have a particularly poor prognosis with conventional chemotherapy (less than 5% survival at 5 years). Such patients may therefore be considered as candidates for experimental treatment approaches, non-intensive therapy or supportive care (reviewed in Grimwade 1 ). In children and younger adults, one key objective of the diagnostic work-up is to distinguish patients at differing risk of relapse to guide the use of allogeneic transplantation in first complete remission (CR). Conventional allografting has been clearly shown to reduce rates of relapse as com- pared to standard intensive chemotherapy (reviewed in Rowe 2 ), although the situation regarding overall survival (OS) is less clear. Given the procedure-related mortality associated with allogeneic transplantation, which is influenced by a range of factors, particularly patient age and type of transplant, one could argue that only those individuals at significant risk of relapse might be expected to gain any potential survival benefit from a transplant delivered in first CR. Accurate prediction of disease prognosis is therefore invaluable to help inform such treatment decisions, given the considerable expense associated with allogeneic transplantation as well as its longer term impact on health and quality of life. Pre-treatment Prognostic Factors Karyotype In approximately 60% of patients with AML, pre-treatment cytogenetic analysis reveals an abnormal karyotype. 1 While ACUTE MYELOID LEUKEMIA _________________________________________________________________________________