Acute myeloid leukemia (AML) is a disorder characterized by a malignancy of the bone marrow stem cell at either a pluripotent or committed stage of development, which leads to an overproliferation of leukemic cells (blasts), which can be shown to have either cytochemical and/or immunophenotypic features of myeloid (including monocytoid, erythroid, or megakaryocytic) lineage. A brief list of the pathophys-iologic abnormalities leading to this malignancy include unbridled proliferation, failure to undergo normal maturation, the inability to undergo programmed cell death, and overreliance on angiogenic mechanisms. The disordered growth in the myeloid stem cell compartment leads to the patient's death from bone marrow failure, unless a successful therapeutic strategy is employed. The fundamental differences in disease biology and clinical response between AML arising in younger (generally considered to be less than 60 years in age) verses older adults have lead to different therapeutic approaches in these groups. This chapter deals with the therapeutic strategies available for those younger adults who are by and large able to withstand (and benefit from) intensive chemotherapy and stem cell transplantation.

The major challenge in the management of the adult, age 18-60 years, with AML is to employ the available therapies in a fashion that will maximize the chance of a cure for any individual. The chance of long-term disease-free survival for an adult in this age group today is approximately 33%.1,2 However, our recent knowledge of risk at presentation, largely due to chromosome findings at diagnosis, suggests that some patients with AML can expect long-term disease-free survival rates in the range of 70%, while others are rarely cured.3 These vastly different prior probabilities of success with available therapy suggest that, with appropriate use of so-called risk-adapted approaches, one could prevent overtreatment in the good prognosis groups and maximize treatment in those destined to do poorly. Moreover, increasing knowledge about the specific pathophysiological events at the genetic level4 also gives rise to the hope that therapy could target the specific genetic lesion or lesions in a given patient's leukemic cells, thereby improving the therapeutic index and leading to a higher cure rate with less toxicity.

0 0

Post a comment