The clinical features and outcomes of elderly patients with acute myeloid leukemia: a real word research.
Clinical and experimental medicine
The aim of this study was to investigate the clinical features and outcomes of elderly patients with acute myeloid leukemia (AML) from a real word research. The clinical data of 223 consecutive elderly patients (aged ≥ 60 years) who were newly diagnosed with AML at our medical center between July 2017 and June 2022, including their clinical characteristics, genetic mutations, and survival outcomes, were retrospectively analyzed. Among the 223 patients (median age 67 years), 180 (80.7%) were diagnosed with de novo AML. Genetic mutations were identified in 138 of 149 patients tested (92.6%). The most commonly mutated genes included TET2, DNMT3A, NPM1, FLT3-ITD, ASXL1, IDH2, RUNX1, TP53, and CEBPA. Among these genes, TET2, DNMT3A, FLT3-ITD, and TP53 were associated with a poor outcome. Multivariate Cox's regression analysis revealed that age over 70 years, platelet count less than 100 × 10/L, albumin level less than 35 g/L, presence of infection or bleeding at diagnosis, untreated or best supportive care (BSC) treatment status, and adverse or intermediate ELN 2022 risk classification were independent prognostic factors for overall survival in elderly AML patients. Patients who received at least one induction cycle had longer overall survival times (20 months vs. 6.6 months, P < 0.001) than those who received best supportive care. Patients with ≥ 6 cycles of chemotherapy had longer overall survival times (89.2% vs. 78.5%, P = 0.007) than those with ≤ 5 cycles of therapy. The results of this study indicated that elderly AML patients had multiple genetic abnormalities and poor outcomes. Regular effective treatment can improve patient outcomes and survival. In addition to genetic abnormalities, several other clinical features can influence survival in elderly AML patients.
10.1007/s10238-024-01536-4
Future directions in myelodysplastic syndromes/neoplasms and acute myeloid leukaemia classification: from blast counts to biology.
Histopathology
Myelodysplastic syndromes/neoplasms (MDS) and acute myeloid leukaemia (AML) are neoplastic haematopoietic cell proliferations that are diagnosed and classified based on a combination of morphological, clinical and genetic features. Specifically, the percentage of myeloblasts in the blood and bone marrow is a key feature that has historically separated MDS from AML and, together with several other morphological parameters, defines distinct disease entities within MDS. Both MDS and AML have recurrent genetic abnormalities that are increasingly influencing their definitions and subclassification. For example, in 2022, two new MDS entities were recognised based on the presence of SF3B1 mutation or bi-allelic TP53 abnormalities. Genomic information is more objective and reproducible than morphological analyses, which are subject to interobserver variability and arbitrary numeric cut-offs. Nevertheless, the integration of genomic data with traditional morphological features in myeloid neoplasm classification has proved challenging by virtue of its sheer complexity; gene expression and methylation profiling also can provide information regarding disease pathogenesis, adding to the complexity. New machine-learning technologies have the potential to effectively integrate multiple diagnostic modalities and improve on historical classification systems. Going forward, the application of machine learning and advanced statistical methods to large patient cohorts can refine future classifications by advancing unbiased and robust previously unrecognised disease subgroups. Future classifications will probably incorporate these newer technologies and higher-level analyses that emphasise genomic disease entities over traditional morphologically defined entities, thus promoting more accurate diagnosis and patient risk stratification.
10.1111/his.15353
[ENT manifestations of myeloid sarcoma].
Revue medicale suisse
Myeloid sarcoma (MS) is a rare extra-medullary manifestation of acute myeloid leukaemia (AML) in the form of a first manifestation, progression or recurrence. Mostly located in the bones, it has the particularity of reaching the ENT sphere by mimicking common patho-logies, leading to a delay in diagnosis and treatment. The -mastoid involvement that we have encountered in our clinical -practice (clinical vignette) shows the complexity of identifying this pathology, with very few cases reported in the literature. The anamnesis, including a -history of AML, and the clinical examination help to guide the investigations. Targeted imaging, in this case CT/MRI combined with a biopsy of the lesion and a marrow puncture, is used to make the -diagnosis. Treatment with chemotherapy is indicated and rapidly initiated.
10.53738/REVMED.2024.20.889.1761
CD45 inhibition in myeloid leukaemia cells sensitizes cellular responsiveness to chemotherapy.
Annals of hematology
Myeloid malignancies are a group of blood disorders characterized by the proliferation of one or more haematopoietic myeloid cell lineages, predominantly in the bone marrow, and are often caused by aberrant protein tyrosine kinase activity. The protein tyrosine phosphatase CD45 is a trans-membrane molecule expressed on all haemopoietic blood cells except that of platelets and red cells. CD45 regulates various cellular physiological processes including proliferation, apoptosis, and lymphocyte activation. However, its role in chemotherapy response is still unknown; therefore, the aim of this study was to investigate the role of CD45 in myeloid malignancies in terms of cellular growth, apoptosis, and response to chemotherapy. The expression of CD45 on myeloid leukaemia primary cells and cell lines was heterogeneous with HEL and OCI-AML3 cells showing the highest level. Inhibition of CD45 resulted in increased cellular sensitivity to cytarabine and ruxolitinib, the two main therapies for AML and MPN. Bioinformatics analysis identified genes whose expression was correlated with CD45 expression such as JAK2, ACTR2, THAP3 Serglycin, and PBX-1 genes, as well as licensed drugs (alendronate, allopurinol, and balsalazide), which could be repurposed as CD45 inhibitors which effectively increases sensitivity to cytarabine and ruxolitinib at low doses. Therefore, CD45 inhibition could be explored as a potential therapeutic partner for treatment of myeloid malignancies in combination with chemotherapy such as cytarabine especially for elderly patients and those showing chemotherapy resistance.
10.1007/s00277-023-05520-y
A practical algorithm for acute myeloid leukaemia diagnosis following the updated 2022 classifications.
Critical reviews in oncology/hematology
Disease classification of complex and heterogenous diseases, such as acute myeloid leukaemia (AML), is continuously updated to define diagnoses, appropriate treatments, and assist research and education. Recent availability of molecular profiling techniques further benefits the classification of AML. The World Health Organization (WHO) classification of haematolymphoid tumours and the International Consensus Classification of myeloid neoplasms and acute leukaemia from 2022 are two updated versions of the WHO 2016 classification. As a consequence, the European LeukemiaNet 2022 recommendations on the diagnosis and management of AML in adults have been also updated. The current review provides a practical interpretation of these guidelines to facilitate the diagnosis of AML and discusses genetic testing, disease genetic heterogeneity, and FLT3 mutations. We propose a practical algorithm for the speedy diagnosis of AML. Future classifications may need to incorporate gene mutation combinations to enable personalised treatment regimens in the management of patients with AML.
10.1016/j.critrevonc.2024.104358
The power and potential of integrated diagnostics in acute myeloid leukaemia.
British journal of haematology
The field of acute myeloid leukaemia (AML) diagnostics, initially based solely on morphological assessment, has integrated more and more disciplines. Today, state-of-the-art AML diagnostics relies on cytomorphology, cytochemistry, immunophenotyping, cytogenetics and molecular genetics. Only the integration of all of these methods allows for a comprehensive and complementary characterisation of each case, which is prerequisite for optimal AML diagnosis and management. Here, we will review why multidisciplinary diagnostics is mandatory today and will gain even more importance in the future, especially in the context of precision medicine. We will discuss ideas and strategies that are likely to shape and improve multidisciplinary diagnostics in AML and may even overcome some of today's gold standards. This includes recent technical advances that provide genome-wide molecular insights. The enormous amount of data obtained by these latter techniques represents a great challenge, but also a unique chance. We will reflect on how this increase in knowledge can be incorporated into the routine to pave the way for personalised medicine in AML.
10.1111/bjh.16360
Phenotypic clues that predict underlying cytogenetic/genetic abnormalities in myeloid malignancies: A contemporary review.
Cytopathology : official journal of the British Society for Clinical Cytology
Precise subclassification of myeloid malignancies per the World Health Organization (WHO) classification system and the International Consensus Classification of Myeloid Neoplasms and Acute Leukaemias (ICC) requires investigation and documentation of the presence of cytogenetic and/or molecular genetic changes. These ancillary studies not only help in diagnosis, but also the prognosis of disease; however, they take time to be completed. In contrast, morphological evaluation of material from the blood and bone marrow specimens of cases where myeloid malignancies are suspected is usually completed quickly. Cytomorphological assessment may predict genetic changes and can be helpful in triaging acuity. This is especially true in haematological emergencies such as acute promyelocytic leukaemia (APL), where prompt APL-specific therapy can be life changing. Similarly, some morphological clues may help identify core binding factor leukaemias where a diagnosis of acute myeloid leukaemia (AML) could be rendered without reaching the 20% blast cutoff with immediate treatment-decision implications, or even a subset of cases of AML with FLT3 ITD/NPM1 mutation(s) which show characteristic features. Even though FISH/cytogenetics and/or PCR are still required for establishing the final diagnosis, evaluation for the presence of specific cytomorphological features that help predict genetic changes can be a useful tool to help guide early therapy.
10.1111/cyt.13280