Modern Risk Stratification of Acute Myeloid Leukemia in 2023: Integrating Established and Emerging Prognostic Factors

Abstract

An accurate estimation of AML prognosis is complex since it depends on patient-related factors, AML manifestations at diagnosis, and disease genetics. Furthermore, the depth of response, evaluated using the level of MRD, has been established as a strong prognostic factor in several AML subgroups. In recent years, this rapidly evolving field has made the prognostic evaluation of AML more challenging. Traditional prognostic factors, established in cohorts of patients treated with standard intensive chemotherapy, are becoming less accurate as new effective therapies are emerging. The widespread availability of next-generation sequencing platforms has improved our knowledge of AML biology and, consequently, the recent ELN 2022 recommendations significantly expanded the role of new gene mutations. However, the impact of rare co-mutational patterns remains to be fully disclosed, and large international consortia such as the HARMONY project will hopefully be instrumental to this aim. Moreover, accumulating evidence suggests that clonal architecture plays a significant prognostic role. The integration of clinical, cytogenetic, and molecular factors is essential, but hierarchical methods are reaching their limit. Thus, innovative approaches are being extensively explored, including those based on “knowledge banks”. Indeed, more robust prognostic estimations can be obtained by matching each patient’s genomic and clinical data with the ones derived from very large cohorts, but further improvements are needed.

Latest Insights and Progress in the Clinical Management of Elderly Patients with Acute Myeloid Leukemia: From Genetic Advancements to Targeted Treatments

“…Consequently, NGS and MFCM tests will likely increase significantly over the next few years to accommodate these new classification schemes and provide precise treatments, especially for older patients. However, most older patients can benefit considerably from tailored agents to biological and molecular targets, requiring these innovative treatment approaches, the appropriate diagnostic evaluation, and the regular monitoring of treatment responses [79][80][81][82][83].…”

“…The accurate estimation of prognosis for AML is complex and depends on patient-related factors, AML manifestations at diagnosis, and disease genetics [83]. While NGS platforms have enhanced our understanding of AML biology, performing these tests is rare in older patients.…”

“…Therefore, they present some limitations, particularly for patients with age-related frailty and comorbidities [85]. As the trend towards using lower intensive treatments for most elderly patients continues, the existing risk stratification guidelines and recommendations for post-remission therapies are limited to a few selected ND AML older patients [83]. However, MRD detection is not a routine practice in older patients with AML due to age-related factors, disease features, and available treatment options.…”

“…While curative therapy for AML has traditionally relied on ICT and allogeneic SCT, these measures are associated with potentially severe complications in older AML patients. Therefore, risk stratification systems are essential in older patients with AML candidates to receive lower-intensity treatments by tailored agents and new effective combinations, facilitating new possibilities in this challenging setting [83].…”

Pharmacological p38 MAPK inhibitor SB203580 enhances AML stem cell line KG1a chemosensitivity to daunorubicin by promoting late apoptosis, cell growth arrest in S-phase, and miR-328-3p upregulation

“…AML is the most common acute malignant hematologic disorder in adults. Cytogenetic and genomic characterizations contributing to AML classification into subgroups, as well as the establishment of clinical risk profile and the stratification of AML patients are revealed to be crucial for prognosis and tailored treatment ( Isidori et al, 2019 , Hou and Tien, 2020 , Boscaro et al, 2023 ). In clinical practice, various modalities of AML treatment are employed, which are commonly drug-based protocols, including standard first-line chemotherapy, targeted therapy, antibody-drug conjugates, hypomethylating agents, and small molecule tyrosine kinase inhibitors ( Miyamoto et al, 2022 , Récher et al, 2022 ).…”