Approaches to minimizing the risk of tMDSAML

It may be appropriate to minimize, where possible, agents that are particularly associated with the greatest risk, including alkylating agents, external beam irradiation and topo-isomerase inhibitors. This can be accomplished in part by the identification of high-risk individuals who are likely to require ASCT as part of their therapy. Recent innovations in the application both of standard prognostic indicators and of global expression arrays may help in the identification of such patients, and efforts to assess risk using molecular markers should be further explored and validated. It seems advisable to avoid TBI as part of the conditioning regimen, although it may be best to directly determine the risk/benefit ratio of using TBI in a randomized trial. If standard cytogenetics are abnormal, allogeneic rather than autologous stem cell transplantation may be indicated. Selected FISH loci, such as 5q, 7q, +8, 20q and -11 should be explored prospectively as predictors of outcome, as should X-inactivation-based clonality assays. Effort should be devoted to pilot retrospective studies to evaluate the role and validity of genome-wide LOH screens, quantitative PCR for specific mutations and gene rearrangements, and the assessment of global expression patterns to identify signatures predictive of t-MDS/AML.

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