Therapy-related acute myelogenous leukemia

Abstract

Therapy-related acute myelogenous leukemia (t-AML) remains difficult to distinguish from de novo leukemia, and the overall incidence of t-AML is expected to increase with the successful management of other malignancies. Cytotoxic chemotherapy and radiation are causes for t-AML. Recent genetic profile data of patients with acute myelogenous leukemia (AML) at the diagnosis suggest that the field may be able to move toward a more refined genetics-based categorization of AML. This may then form the framework for an unbiased approach to the clinical management of t-AML. Cytogenetic abnormalities of t-AML mainly determine the course of disease as it does in de novo AML. Although an inferior outcome is observed in the entire population of t-AML patients, patient outcome is multifactorial. T-AML patients with favorable recurrent cytogenetic abnormalities who received a topoisomerase inhibitor 1-2 years earlier show similar responses to conventional therapy as their de novo counterparts, and patients should be encouraged to participate in clinical trials designed for de novo AML patients with similar cytogenetic abnormalities. T-AML patients who received an alkylating agent or irradiation 3-6 years earlier usually have a complex karyotype in their blast cells, and respond poorly to conventional AML therapy. Persistence of a primary malignancy, decreased organ reserve from prior therapy, and comorbidities impact clinical outcomes and limit therapeutic options for t-AML independent of genetics. Improvements in clinical outcomes in t-AML will be aided by earlier diagnosis and treatment, development of effective lower intensity treatments, post-remission strategies including investigational therapy, and pursuit of transplantation for poor-risk cytogenetic subsets.