AML in the elderly.

The incidence of AML increases with advancing age. 

The median age of patient’s diagnosis of AML is 68 years. 

A large proportion of patients with the AML are older persons, variably defined as 60 to 65 years of age and older.

In young and fit individuals standard treatments consists of intensive chemotherapy combining cytarabine and an antracycline, with or without consolidative allogeneic hematopoetic stem cell transplant.

Treating AML the elderly is difficult because of the incidence of frailty and medical comorbidities, and poor risk disease features such as adverse cytogenetics, complex karyotypes, 

TP53 mutations,  therapy related AML, antecedent myelodysplastic syndrome are more common in the elderly. 

Treatment with hypomethhalating agents azacitadine and decitabine have been previously considered the standard of care for older patients who are unfit for intensive care intensive chemotherapy.

Hypomethhalating agents are generally well-tolerated in older patients, the rates of complete remission are modest at 15 to 20%.

In patients with Core binding factor AML, elderly patients should be offered intensive cytarabine based chemotherapy, is it represents an opportunity for cure.

Ore binding factor AML is marked by t(8:21) or INV 16 translocations, defines a subset of patients with favorable outcomes and treatment with traditional intensive induction chemotherapy.

Gemtuzumab ozogamicin is an anti-CD  33 antibody drug conjugate has significantly improved outcomes in this subgroup of patients when combined with induction chemotherapy.

In older patients with AML who are medically fit and have a suitable donor long-term disease control may be achieved with allogeneic hematopoietic stem cell transplant.

For unfit elderly patients with AML azacididine plus venetoclax are considered.

Cladribine and clofarabine are purine nucleoside analogues that inhibit ribonucleotide reductase, leading to DNA leading to deoxynucleotide depletion and inhibition of DNA synthesis and is an effective regimen of low intensity with high efficacy and low toxicity in the elderly.

FLT3 mutation AML occurs less commonly in the elderly but is responsive to Midostaurin, gilteritinib and sorafenib.

IDH1/2 gene mutations are identified in 15 to 20% of cases of AML.

Ivosidenib, azacitidine, enasidenib IDH inhibitors are moderately effective agents.

Outcomes in patients who have AML with TP53 mutations, which are often associated with adverse/complex karyotypes are consistently poor with current treatment.

High dose cytarabine and an allogeneic hematopoetic stemcell transplant are the two best consolidation strategies in AML: The elderly are often ineligible for such therapies.

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