Abstract
Hematopoietic stem cell transplantation (HSCT) is a curative treatment for several malignant and nonmalignant disorders. Busulfan (Bu) and cyclophosphamide (Cy) are the most commonly used alkylators in high-dose pretransplant conditioning for HSCT; a treatment that is correlated with drug-related toxicity and relapse. Pharmacogenetic investigations have shown that CYP450, as well as aldehyde dehydrogenase, are clearly involved with Cy metabolism and are associated with altered treatment response, Cy metabolism and the unique stem-cell sparing capacity. Moreover, glutathione-S-transferase isoenzymes have been associated with cellular outward transport of various alkylating agents, including Cy metabolites, melphalan, Bu and chlorambucil. A shift from genetic-based studies to whole-genome-based investigations of Cy- and Bu-associated markers may contribute to personalizing the conditioning therapy and enhancing the clinical outcome of HSCT.
Published Version
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