Environmental Chemistry and Engineering

Biography

Biography: Emmanuel C Besa

Abstract

Although not all patients with myelodysplastic syndrome (MDS) evolve into acute myelogenous leukemia (AML), it is generally believed that these patients if they survive long enough will eventually transform and was in the past named as a preleukemic syndrome. Basic knowledge regarding the molecular mechanism of the evolution of MDS into AML, development of epigenetic and immunomodulatory agents in its management may give us opportunities of better management of the disease as well as opportunities to prevention of its evolution to a fatal condition given the right circumstances. Continued improvement in classification and prognostication by inclusion of new data including cytogenetics and molecular markers, we are now able to tailor specific treatment for subgroups of patients who share similar diagnostic labels but differ in pathogenesis as indicated by their molecular markers leading to a more specific and personal approach to their management. A specific example in MDS is the presence of a cytogenetic abnormality ie. del5q which is responsive to a specific immunomodulatory agent called lenalidomide (an analogue of thalidomide). This syndrome which for the past decade had no standard therapy that prolonged survival has now shown a doubling overall survival with azacytidine, a demethylating agent. Meanwhile in AML, specific cytogenetic abnormalities have led to a completely different approach such as using a retinoid and arsenic trioxide for acute promyelocytic leukemia (APL) with the specific cytogenetic abnormality of a translocation 15;17. We also now identified AML patients with cytogenetic abnormalities of the core binding factor such as inverted 16 as a good prognostic marker and treated specifically with standard induction and high dose cytosine arabinoside consolidation. The intermediate group in AML with normal cytogenetics is a mixture of good and bad prognostic patients and with the help of molecular markers such as FLT3/ITD and NPM markers, we are able to tease out the good from the bad and plan out a more specific approach to their management. We an also identify up front patients who will not respond to our available therapies and should be prepared early for possible hematopoietic stem cell transplantation. The latter has evolved so that we can now push this form of treatment to include some of our elderly patients using less aggressive non-myeloablative approaches and using graft versus leukemia effects to our advantage.