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Rhode Island Medical Journal (2013) Apr 2020Acute myeloid leukemia (AML) is a malignancy of the stem cell precursors of the myeloid lineage (red blood cells, platelets, and white blood cells other than B and T... (Review)
Review
Acute myeloid leukemia (AML) is a malignancy of the stem cell precursors of the myeloid lineage (red blood cells, platelets, and white blood cells other than B and T cells). Like other malignancies, it is due to genetic variations that lead to neoplastic changes and clonal proliferation. AML remains a rare malignancy, accounting for only 1.2% of all new cancer diagnoses in the United States per year, but it accounts for close to one third of all leukemias diagnosed.* For much of the 20th and early 21st century treatment paradigms were unchanged with survival curves remaining stagnant for many decades. Recent changes in our understanding of the genetic variations in the disease have led to some promising new therapies with hopes for improved outcomes in the future. Below we review the definitions, diagnosis and classification of AML and how this affects the evolving treatment paradigm of AML.
Topics: Antineoplastic Agents; Forecasting; Hematopoietic Stem Cell Transplantation; Humans; Leukemia, Myeloid, Acute; Recurrence; Treatment Outcome
PubMed: 32236160
DOI: No ID Found -
BMJ (Clinical Research Ed.) Oct 2021Acute myeloid leukemia (AML) is an uncommon but potentially catastrophic diagnosis with historically high mortality rates. The standard of care treatment remained... (Review)
Review
Acute myeloid leukemia (AML) is an uncommon but potentially catastrophic diagnosis with historically high mortality rates. The standard of care treatment remained unchanged for decades; however, recent discoveries of molecular drivers of leukemogenesis and disease progression have led to novel therapies for AML. Ongoing research and clinical trials are actively seeking to personalize therapy by identifying molecular targets, discovering patient specific and disease specific risk factors, and identifying effective combinations of modalities and drugs. This review focuses on important updates in diagnostic and disease classifications that reflect new understanding of the biology of AML, its mutational heterogeneity, some important genetic and environmental risk factors, and new treatment options including cytotoxic chemotherapy, novel targeted agents, and cellular therapies.
Topics: Antineoplastic Agents; Combined Modality Therapy; Disease Progression; Genetic Predisposition to Disease; Hematopoietic Stem Cell Transplantation; Humans; Immunotherapy; Leukemia, Myeloid, Acute; Molecular Targeted Therapy
PubMed: 34615640
DOI: 10.1136/bmj.n2026 -
Haematologica Feb 2023Research into the underlying pathogenic mechanisms of acute myeloid leukemia (AML) has led to remarkable advances in our understanding of the disease. Mutations now... (Review)
Review
Research into the underlying pathogenic mechanisms of acute myeloid leukemia (AML) has led to remarkable advances in our understanding of the disease. Mutations now allow us to explore the enormous diversity among cytogenetically defined subsets of AML, particularly the large subset of cytogenetically normal AML. Despite the progress in unraveling the tumor genome, only a small number of recurrent mutations have been incorporated into risk-stratification schemes and have been proven to be clinically relevant, targetable lesions. The current World Health Organization Classification of myeloid neoplasms and leukemia includes eight AML categories defined by recurrent genetic abnormalities as well as three categories defined by gene mutations. We here discuss the utility of molecular markers in AML in prognostication and treatment decision-making. New therapies based on targetable markers include IDH inhibitors (ivosidenib, enasidenib), venetoclax-based therapy, FLT3 inhibitors (midostaurin, gilteritinib, and quizartinib), gemtuzumab ozogamicin, magrolimab and menin inhibitors.
Topics: Humans; Leukemia, Myeloid, Acute; Gemtuzumab
PubMed: 36722402
DOI: 10.3324/haematol.2022.280801 -
Current Oncology (Toronto, Ont.) Aug 2022Acute myeloid leukemia (AML) is a hematologic malignancy that most frequently develops in older adults. Overall, AML is associated with a high mortality although... (Review)
Review
Acute myeloid leukemia (AML) is a hematologic malignancy that most frequently develops in older adults. Overall, AML is associated with a high mortality although advancements in genetic risk stratification and new treatments are leading to improvements in outcomes for some subgroups. In this review, we discuss an individualized approach to intensive therapy with a focus on the role of recently approved novel therapies as well as the selection of post-remission therapies for patients in first remission. We discuss the management of patients with relapsed and refractory AML, including the role of targeted treatment and allogeneic stem cell transplant. Next, we review non-intensive treatment for older and unfit AML patients including the use of azacitidine and venetoclax. Finally, we discuss the integration of palliative care in the management of patients with AML.
Topics: Aged; Azacitidine; General Practitioners; Hematopoietic Stem Cell Transplantation; Humans; Leukemia, Myeloid, Acute
PubMed: 36135060
DOI: 10.3390/curroncol29090491 -
Seminars in Diagnostic Pathology May 2023Myeloid Sarcoma (MS) is a high grade, hematological malignancy defined as an extramedullary tumor mass of myeloid blasts with or without maturation that effaces tissue... (Review)
Review
Myeloid Sarcoma (MS) is a high grade, hematological malignancy defined as an extramedullary tumor mass of myeloid blasts with or without maturation that effaces tissue architecture. It is a highly heterogenous condition that represents a variety of myeloid neoplasms. This heterogeneity of MS, together with its rarity, have greatly hampered our understanding of the condition. Diagnosis requires tumor biopsy, which should be accompanied by bone marrow evaluation for medullary disease. It is presently recommended that MS be treated similar to AML. Additionally, ablative radiotherapy and novel targeted therapies may also be beneficial. Genetic profiling has identified recurrent genetic abnormalities including gene mutations associated with MS, supporting its etiology similar to AML. However, the mechanisms by which MS homes to specific organs is unclear. This review provides an overview of pathogenesis, pathological and genetic findings, treatment, and prognosis. Improving the management and outcomes of MS patients requires a better understanding of its pathogenesis and its response to various therapeutic approaches.
Topics: Humans; Sarcoma, Myeloid; Prognosis; Myeloproliferative Disorders; Mutation; Leukemia, Myeloid, Acute
PubMed: 37149396
DOI: 10.1053/j.semdp.2023.04.009 -
Acta Haematologica 2024Acute myeloid leukemia (AML) is a biologically heterogenous disease arising in clonally proliferating hematopoietic stem cells. Sequential acquisition of mutations leads... (Review)
Review
BACKGROUND
Acute myeloid leukemia (AML) is a biologically heterogenous disease arising in clonally proliferating hematopoietic stem cells. Sequential acquisition of mutations leads to expanded proliferation of clonal myeloid progenitors and failure of differentiation, leading to fulminant AML.
SUMMARY
Here, we review the pathophysiology of AML with a focus on factors predisposing to AML development, including prior chemo- and radiation therapy, environmental factors, and germline predisposition.
KEY MESSAGE
Increasing genomic characterization of AML and insight into mechanisms of its development will be critical to improvement in AML prognostication and therapy.
Topics: Humans; Hematopoietic Stem Cells; Leukemia, Myeloid, Acute; Cell Differentiation; Genotype
PubMed: 38228114
DOI: 10.1159/000536152 -
Current Opinion in Pediatrics Feb 2020Despite advances in therapy over the past decades, overall survival for children with acute myeloid leukemia (AML) has not exceeded 70%. In this review, we highlight... (Review)
Review
PURPOSE OF REVIEW
Despite advances in therapy over the past decades, overall survival for children with acute myeloid leukemia (AML) has not exceeded 70%. In this review, we highlight recent insights into risk stratification for patients with pediatric AML and discuss data driving current and developing therapeutic approaches.
RECENT FINDINGS
Advances in cytogenetics and molecular profiling, as well as improvements in detection of minimal residual disease after induction therapy, have informed risk stratification, which now relies heavily on these elements. The treatment of childhood AML continues to be based primarily on intensive, conventional chemotherapy. However, recent trials focus on limiting treatment-related toxicity through the identification of low-risk subsets who can safely receive fewer cycles of chemotherapy, allocation of hematopoietic stem-cell transplant to only high-risk patients and optimization of infectious and cardioprotective supportive care.
SUMMARY
Further incorporation of genomic and molecular data in pediatric AML will allow for additional refinements in risk stratification to enable the tailoring of treatment intensity. These data will also dictate the incorporation of molecularly targeted therapeutics into frontline treatment in the hope of improving survival while decreasing treatment-related toxicity.
Topics: Antineoplastic Agents; Child; Hematopoietic Stem Cell Transplantation; Humans; Leukemia, Myeloid, Acute; Molecular Targeted Therapy; Patient Care; Prognosis; Risk Assessment; Risk Factors
PubMed: 31815781
DOI: 10.1097/MOP.0000000000000855 -
Annals of Hematology Aug 2023Myeloid sarcoma (MS) is a distinct entity among myeloid neoplasms defined as a tumour mass of myeloid blasts occurring at an anatomical site other than the bone marrow,... (Review)
Review
Myeloid sarcoma (MS) is a distinct entity among myeloid neoplasms defined as a tumour mass of myeloid blasts occurring at an anatomical site other than the bone marrow, in most cases concomitant with acute myeloid leukaemia (AML), rarely without bone marrow involvement. MS may also represent the blast phase of chronic myeloproliferative neoplasms (MPN) and myelodysplastic syndromes (MDS). However, the clinical and molecular heterogeneity of AML, as highlighted by the 2022 World Health Organization (WHO) and International Consensus (ICC) classifications, indirectly define MS more as a set of heterogeneous and proteiform diseases, rather than a homogeneous single entity. Diagnosis is challenging and relies mainly on histopathology, immunohistochemistry, and imaging. Molecular and cytogenetic analysis of MS tissue, particularly in isolated cases, should be performed to refine the diagnosis, and thus assign prognosis guiding treatment decisions. If feasible, systemic therapies used in AML remission induction should be employed, even in isolated MS. Role and type of consolidation therapy are not univocally acknowledged, and systemic therapies, radiotherapy, or allogeneic hematopoietic stem cell transplantation (allo-HSCT) should be considered. In the present review, we discuss recent information on MS, focusing on diagnosis, molecular findings, and treatments also considering targetable mutations by recently approved AML drugs.
Topics: Humans; Sarcoma, Myeloid; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Myeloproliferative Disorders; Hematopoietic Stem Cell Transplantation
PubMed: 37286874
DOI: 10.1007/s00277-023-05288-1 -
Blood Reviews May 2021The World Health Organization classification and definition of "myeloid sarcoma" is imprecise and misleading. A more accurate term is "extramedullary acute myeloid... (Review)
Review
The World Health Organization classification and definition of "myeloid sarcoma" is imprecise and misleading. A more accurate term is "extramedullary acute myeloid leukemia tumor (eAML)." The pathogenesis of eAML has been associated with aberrancy of cellular adhesion molecules, chemokine receptors/ligands and RAS-MAPK/ERK signaling. eAML can present with or without synchronous or metachronous intramedullary acute myeloid leukemia (AML) so a bone marrow evaluation is always recommended. Accurate diagnosis of eAML requires tissue biopsy. eAML confined to one or a few sites is frequently treated with local therapy such as radiotherapy. About 75-90% of patients with isolated eAML will develop metachronous intramedullary AML with a median latency period ranging from 4 to 12 months; thus, patients with isolated eAML may also be treated with systemic anti-leukemia therapy. eAML does not appear to have an independent prognostic impact; selection of post-remission therapy including allogeneic hematopoietic cell transplant (alloHCT) is typically guided by intramedullary disease risk. Management of isolated eAML should be individualized based on patient characteristics as well as eAML location and cytogenetic/molecular features. The role of PET/CT in eAML is also currently being elucidated. Improving outcomes of patients with eAML requires further knowledge of its etiology and mechanism(s) as well as therapeutic approaches beyond conventional chemotherapy, ideally in the context of controlled trials.
Topics: Allografts; Hematopoietic Stem Cell Transplantation; Humans; Leukemia, Myeloid, Acute; MAP Kinase Signaling System; Neoplasm Proteins; Positron Emission Tomography Computed Tomography; Radiotherapy; Sarcoma, Myeloid
PubMed: 33213985
DOI: 10.1016/j.blre.2020.100773 -
British Journal of Haematology Jan 2020The field of acute myeloid leukaemia (AML) diagnostics, initially based solely on morphological assessment, has integrated more and more disciplines. Today,... (Review)
Review
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.
Topics: Cytogenetic Analysis; Genome-Wide Association Study; Humans; Immunophenotyping; Leukemia, Myeloid, Acute; Precision Medicine
PubMed: 31808952
DOI: 10.1111/bjh.16360