Drugs, such as chloramphenicol, phenylbutazone, chloroquine, and methoxypsoralen, can induce marrow damage that may later evolve into AML. Secondary AML may also occur because of progression of myelodysplastic syndrome or chronic bone marrow stem cell disorders, such as polycythemia bcr-abl vera, chronic myeloid leukemia, primary thrombocytosis, or paroxysmal nocturnal hemoglobinuria. Secondary AML has a particularly poor prognosis and is not considered to be curable, with the exception of secondary acute promyelocytic leukemia. This is largely due to the high percentage of secondary AML associated with multidrug resistance mechanisms: up to 70% of secondary AML patients show overexpression of P glycoprotein or other MDR mechanisms.
The genetic changes in leukemic blasts make them ineffective at generating mature red blood cells, neutrophils, monocytes, and platelets. In addition, these AML blasts also inhibit normal blasts from differentiating Doxorubicin structure into mature progeny. Inhibition does not result from crowding out of normal blasts, rather, inhibition may be mediated by various chemokines produced by AML blasts. AML progresses rapidly and is typically fatal within weeks or months if left untreated. The most common cause of death in AML is bone marrow failure, and the principal sign of marrow failure is infection. Potential fatal organ infiltration, most commonly involving the lung and the brain, becomes more likely as the disease progresses. AML is the most common acute leukemia affecting adults, and its incidence increases with age.
Although the majority of patients under age 60 years achieve complete remission with traditional anthracycline and cytarabine based induction regimens, the long term survival rates continue to be poor at approximately 30% to 40%. The prognosis is even poorer for those with high risk AML, such as those Meristem who are older, those who had preceding MDS or myeloproliferative disorders, or those with secondary AML from environmental exposures or prior chemotherapy. In such cases, CR is achieved in less than 40% of cases, with survival rates of less than 10%. While 60% to 80% of younger patients achieve CR with standard therapy, only about 20% to 30% of the overall patient population has long term disease free survival. Outcomes are worse for patients aged 60 years or over, with CR rates in the range of 40% to 55% and poor long term survival rates.
Along with age, remission rates and overall survival depend on a number of other factors, including cytogenetics, previous bone marrow disorders such as MDS, and comorbidities. AML accounts for approximately 25% of all leukemias diagnosed in adults, and the median age at diagnosis is 67 years. In the United States, 43,050 new cases of leukemia were reported in the year 2010, of which BI-1356 molecular weight 12,330 were new cases of AML. There were 21,840 patients who died in the year 2010 because of leukemia, of which 8,950 were attributed to AML. The incidence of AML in the 65 years age group is 1. 8 cases per 100,000 patients, and the incidence in the 65 years age group is 17. 9 cases per 100,000 patients.