Epidemiological, genetic, and clinical characterization by age of newly diagnosed acute myeloid leukemia based on an academic population-based registry study (AMLSG BiO)

Abstract

We describe genetic and clinical characteristics of acute myeloid leukemia (AML) patients according to age from an academic population-based registry. Adult patients with newly diagnosed AML at 63 centers in Germany and Austria were followed within the AMLSG BiO registry (NCT01252485). Between January 1, 2012, and December 31, 2014, data of 3525 patients with AML (45% women) were collected. The median age was 65 years (range 18–94). The comparison of age-specific AML incidence rates with epidemiological cancer registries revealed excellent coverage in patients < 70 years old and good coverage up to the age of 80. The distribution according to the European LeukemiaNet (ELN) risk categorization from 2010 was 20% favorable, 31% intermediate-1, 28% intermediate-2, and 21% adverse. With increasing age, the relative but not the absolute prevalence of patients with ELN favorable and intermediate-1 risk (p < 0.001), with activating FLT3 mutations (p < 0.001), with ECOG performance status < 2 (p < 0.001), and with HCT-CI comorbidity index < 3 (p < 0.001) decreased. Regarding treatment, obesity and favorable risk were associated with an intensive treatment, whereas adverse risk, higher age, and comorbidity index > 0 were associated with non-intensive treatment or best supportive care. The AMLSG BiO registry provides reliable population-based distributions of genetic, clinical, and treatment characteristics according to age.Electronic supplementary materialThe online version of this article (10.1007/s00277-017-3150-3) contains supplementary material, which is available to authorized users.

Acute myelogenous leukemia in adolescents and young adults

“…The high incidence of AML in older age groups (especially >60 years) correlates with prolonged exposure to environmental carcinogens and accumulation of mutations from genetic error events in cell division . The incidence of acute promyelocytic leukemia (APL, t[15;17]/ PML‐RARA , World Health Organization 2008 classification) and AML with NPM1 mutations appears constant with respect to age after the first decade . According to SEER data, the proportion of APL is highest (20–25%) among AML subtypes in AYA (Figure ).…”

“…This trend remained in recent analyses (1997–2005; up to 45% in 5‐ to 10‐year‐old children vs. 14% in adolescents, and <5% in older AYA) and was mainly because these patients were not referred to institutions undertaking the clinical trials . In Europe, participation rates are higher in AYA with leukemias, as they are generally included in national trials (e.g., >90% in the British MRC trials or German AML trials) . As most clinical trials in adults do not report results separately for AYA and older adults, limited data are available for comparisons across age groups.…”

Temporal patterns and predictors of receiving no active treatment among older patients with acute myeloid leukemia in the United States: A population‐level analysis

“…Treatment modalities with the highest cure rates, namely intensive chemotherapy and allogeneic hematopoietic stem cell transplantation, are mainly reserved for younger patients . In addition, AML in older patients is associated with adverse cytogenetics and lower response rates, leading to a poor median overall survival of 3 to 6 months …”

“…2,3 In addition, AML in older patients is associated with adverse cytogenetics and lower response rates, leading to a poor median overall survival of 3 to 6 months. 2,[4][5][6] Although high-intensity treatment with curative intent might not be feasible for older patients with AML, several treatment options to alleviate symptoms, improve quality of life (QOL), reduce the need for transfusion, and possibly prolong survival are available. [2][3][4] These include hypomethylating agents (HMAs) such as azacitidine and decitabine, lowdose cytarabine, and, more recently, targeted therapies such as the hedgehog signaling pathway inhibitor glasdegib and the BCL-2 inhibitor venetoclax, which have been approved in the United States for older, unfit patients with AML.…”

“…12 The underlying factors for the potential undertreatment of older patients with AML include a high burden of comorbidity, poor performance status, and the adverse genetic profile of the disease. 5,12 Given the heterogeneity of both patients with AML and the disease biology as well as the greater availability of targeted and less toxic therapies, it is widely recommended that age alone should not be used as the sole criterion with which to make treatment decisions. 5,13,14 One of the major reasons leading clinicians to limit active treatment in elderly patients with AML is the concern for treatment-associated toxicity and impaired QOL.…”