Question ID: WS-44
Submitted by: Lindsay Morton
February 7, 2011
What is the risk of treatment-related leukemia associated with the many new chemotherapeutic, biologic, and molecularly-targeted agents that have been introduced in recent decades? Which patients are particularly susceptible to developing treatment-related leukemia? Background: Treatment-related myelodysplastic syndrome/acute myeloid leukemia (t-MDS/AML) is a rare but highly fatal complication of cytotoxic chemotherapy. Certain chemotherapeutic agents are known to be leukemogenic (e.g., melphalan, doxorubicin) and are associated with distinct morphologic and clinical characteristics and cytogenetic abnormalities. However, the dose-response relationship and mechanism are not well established; the leukemogenicity of newer chemotherapeutic, biologic, and molecularly-targeted agents is unknown; and patients who may be particularly susceptible to t-MDS/AML cannot currently be identified. With the increasing use of chemotherapy and improved survival of cancer patients, better understanding the risks and benefits of treatment has important clinical implications. Feasibility: Several large clinical series have provided valuable information about the morphologic, clinical characteristics, and cytogenetic abnormalities typical of t-MDS/AML arising after exposure to different classes of chemotherapeutic agents. The introduction of newer chemotherapeutic, biologic, and molecularly-targeted agents as well as descriptive studies showing changing incidence patterns of t-AML that are consistent with changing treatment practices demonstrate an urgent need for additional study. Newly created registries of patients with t-MDS/AML and follow-up of clinical trials or patients within health maintenance organizations may provide populations in which t-MDS/AML can be studied. Implications of success: Quantification of the risks of t-MDS/AML for newer cancer treatments would provide important information for clinicians assessing treatment risks and benefits. Identifying patients who are particularly susceptible to developing t-MDS/AML would allow for more personalized medicine, with risk/benefit calculations taking into account inherited susceptibility to a highly fatal complication of treatment. Further research in this area should also advance understanding of the mechanisms of t-MDS/AML, which may shed light on the leukemogenic process in primary AML.
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