Bad prognosis in AML Is indicated by
Correct Answer: Monosomy
Description: Acute myeloid leukemia (AML) with monosomy 7 is associated with poor disease-free survival when treated by aggressive conventional chemotherapy alone. Similarly, outcomes are poor in children with myelodysplastic syndrome (MDS) with monosomy 7 treated by chemotherapy, immunosuppressive drugs or suppoive measures Myelodysplastic syndrome AML arising from a pre-existing myelodysplastic syndrome (MDS) or myeloproliferative disease (so-called secondary AML) has a worse prognosis, as does treatment-related AML arising after chemotherapy for another previous malignancy. Both of these entities are associated with a high rate of unorable cytogenetic abnormalities Cytogenetics The single most impoant prognostic factor in AML is cytogenetics, or the chromosomal structure of the leukemic cell. Ceain cytogenetic abnormalities are associated with very good outcomes (for example, the (15;17) translocation in acute promyelocytic leukemia). About half of people with AML have "normal" cytogenetics; they fall into an intermediate risk group. A number of other cytogenetic abnormalities are known to associate with a poor prognosis and a high risk of relapse after treatment. Genotype A large number of molecular alterations are under study for their prognostic impact in AML. However, only FLT3-ITD, NPM1, CEBPA and c-KIT are currently included in validated international risk stratification schema. These are expected to increase rapidly in the near future. FLT3 internal tandem duplications (ITDs) have been shown to confer a poorer prognosis in AML with normal cytogenetics. Several FLT3 inhibitors have undergone clinical trials, with mixed results. Two other mutations - NPM1 and biallelic CEBPA are associated with improved outcomes, especially in people with normal cytogenetics and are used in current risk stratification algorithms. Researchers are investigating the clinical significance of c-KIT mutations in AML. These are prevalent, and potentially clinically relevant because of the availability of tyrosine kinase inhibitors, such as imatinib and sunitinib that can block the activity of c-KIT pharmacologically. It is expected that additional markers (e.g., RUNX1, ASXL1, and TP53) that have consistently been associated with an inferior outcome will soon be included in these recommendations. The prognostic impoance of other mutated genes (e.g., DNMT3A, IDH1, IDH2) is less clear. Ref Davidson 23rd edition pg 789
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