Highrisk

High-risk MDS, for this discussion, refers to patients belonging to the intermediate-2 (int-2) or high-risk International Prognostic Scoring System (IPSS) categories. As blast cells in these patients are continuously increasing and the probability of transforming into acute myeloid leukemia (AML) is high, therapeutic intervention is essential. Chemotherapeutic agents have traditionally been used, especially busulfan, VP-16, topotecan, and low-dose cytosine arabinoside alone or in combination.1 More recently, a better understanding of the molecular mechanisms underlying the evolution of malignancy has produced new classes of drugs that have proved to be quite successful. These drugs, in addition to DNA methyl-transferase inhibitors, include histone deacetylase (HDAC) inhibitors, farnesyl transferase inhibitors (FTIs), tyrosine kinase inhibitors (TKIs), and arsenic trioxide (ATO). The cellular targets of these drugs are varied and include, either singly or in combination, the chromatin structure of the MDS cell, cytoplasmic regulatory proteins that are essential for cell proliferation, survival, and cell death, and cellular receptors that respond to cytokines of the bone marrow microenvironment.

0 0

Post a comment