The clinical utility of the test refers to the likelihood that the test will, by prompting an intervention, result in an improved health outcome. The clinical utility of a genetic test is based on the health benefits related to the interventions offered to people with positive test results. Theoretically, there are at least five strategies that might improve the health outcome of people with a genetic susceptibility to cancer:
Correction of the underlying genetic defect (not currently available)...
Advances in the treatment of AML (also called acute myelogenous leukemia, acute nonlymphocytic leukemia [ANLL]) have resulted in substantially improved complete remission (CR) rates. Treatment should be sufficiently aggressive to achieve CR because partial remission offers no substantial survival benefit. Approximately 60% to 70% of adults with AML can be expected to attain CR status following appropriate induction therapy. More than 25% of adults with AML (about 45% of those who attain CR) can be expected to survive 3 or more years and may be cured. Remission rates in adult AML are inversely related to age, with an expected remission rate of more than 65% for those younger than 60 years. Data suggest that once attained, duration of remission may be shorter in older patients. Increased morbidity and mortality during induction appear to be directly related to age. Other adverse prognostic factors include central nervous system involvement with leukemia, systemic infection at diagnosis, elevated white blood cell count (>100,000/mm3), treatment-induced AML, and history of myelodysplastic syndromes or another antecedent hematological disorder. Patients with leukemias that express the progenitor cell antigen CD34 and/or the P-glycoprotein (MDR1 gene product) have an inferior outcome.[2,3,4] AML associated with an internal tandem duplication of the FLT3 gene (FLT3/ITD mutation) has an inferior outcome that is attributed to a higher relapse rate.[5,6]
Cytogenetic analysis provides some of the strongest prognostic information available, predicting outcome of both remission induction and postremission therapy, as seen in a trial from the Southwest Oncology Group (SWOG) and the Eastern Cooperative Oncology Group (ECOG) (E-3489). Cytogenetic abnormalities that indicate a good prognosis include t(8; 21), inv(16) or t(16;16), and t(15;17). Normal cytogenetics portend average-risk AML. Patients with AML that is characterized by deletions of the long arms or monosomies of chromosomes 5 or 7; by translocations or inversions of chromosome 3, t(6; 9), t(9; 22); or by abnormalities of chromosome 11q23 have particularly poor prognoses with chemotherapy. These cytogenetic subgroups, as seen in the trial from the Medical Research Council (MRC-LEUK-AML11), predict clinical outcome in older patients with AML as well as in younger patients. The fusion genes formed in t(8; 21) and inv(16) can be detected by reverse transcriptase–polymerase chain reaction (RT–PCR) or fluorescence in situ hybridization (FISH), which will indicate the presence of these genetic alterations in some patients in whom standard cytogenetics was technically inadequate. RT–PCR does not appear to identify significant numbers of patients with good-risk fusion genes who have normal cytogenetics.