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British Journal of Haematology Mar 2011The majority of patients with acute myeloid leukaemia (AML) are elderly. Advancements in supportive care and regimen intensification have resulted in improvements in... (Review)
Review
The majority of patients with acute myeloid leukaemia (AML) are elderly. Advancements in supportive care and regimen intensification have resulted in improvements in clinical outcomes for younger AML patients, but analogous improvements in older patients have not been realized. While outcomes are compromised by increased comorbidities and susceptibility to toxicity from therapy, it is now recognized that elderly AML represents a biologically distinct disease that is more aggressive and less responsive to therapy. Some patients tolerate and benefit from intensive remission-induction approaches, while others are best managed with less aggressive strategies. The challenge is to differentiate these groups based on host-related and biological features, in order to maximize the therapeutic benefit and minimize toxicity. As more is understood about the complicated pathogenesis and molecular basis of AML, there are more opportunities to develop and test targeted therapies. Elderly patients, with their narrow therapeutic window, are well positioned to derive a benefit from these novel agents, and therefore, despite a difficult past, there are reasons to be optimistic about the future of elderly AML.
Topics: Aged; Antineoplastic Agents; Hematopoietic Stem Cell Transplantation; Humans; Leukemia, Myeloid, Acute; Prognosis
PubMed: 21314823
DOI: 10.1111/j.1365-2141.2010.08470.x -
Journal of Internal Medicine Aug 2021The definition of older age in AML is arbitrary. In the context of the clinical studies, it starts with age ≥60 or ≥65 years and in recent years ≥70 or 75,... (Review)
Review
The definition of older age in AML is arbitrary. In the context of the clinical studies, it starts with age ≥60 or ≥65 years and in recent years ≥70 or 75, depending on the selection of the studied population. In clinical practice, with older age, we often mean that the patient is unfit for intensive chemotherapy. Higher age overlaps with categories such as worse performance status, unfitness, comorbidities, poor-risk cytogenetics, adverse mutation patterns, age-related clonal haematopoiesis and specific disease ontogeny. Intensive induction therapy can result in prolonged overall survival, at least in a subset of elderly patients aged up to 75 years despite the reluctance of some physicians and patients to use treatment regimens perceived as toxic. Venetoclax and azacitidine combination is the new standard of comparison for persons unfit for intensive therapy. New oral hypomethylating agent CC-486 as maintenance therapy led to a prolonged overall survival in a randomized trial of patients ≥55 years of age who were in first complete remission, but not eligible for allogeneic stem cell transplantation. Any therapy is better than no therapy, but a substantial proportion of older patients still receive only palliative care. Making a decision for AML diagnosed in older age should be individualized and shared through the dialog with the patient and relatives or cohabitants, considering medical issues and social factors including personal goals. Although we are witnesses of the advances in basic research and therapy, we are still a very long way from curing older patients with AML.
Topics: Age Factors; Aged; Female; Health Status; Humans; Leukemia, Myeloid, Acute; Male; Middle Aged; Socioeconomic Factors
PubMed: 33780573
DOI: 10.1111/joim.13293 -
Nature Reviews. Clinical Oncology Feb 2013
Review
Topics: Combined Modality Therapy; Humans; Leukemia, Myeloid, Acute; Molecular Targeted Therapy; Time Factors
PubMed: 23296115
DOI: 10.1038/nrclinonc.2012.239 -
Lancet (London, England) Sep 1949
Topics: Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid
PubMed: 18140703
DOI: No ID Found -
Blood Reviews Jan 2011Acute myeloid leukaemia (AML) is one of the most common haematological malignancies and is increasing in frequency due to an ageing population. Whilst remission will be... (Review)
Review
Acute myeloid leukaemia (AML) is one of the most common haematological malignancies and is increasing in frequency due to an ageing population. Whilst remission will be achieved in up to 80% of those receiving intensive chemotherapy, the main variables precluding cure are the treatment-related mortality and relapse rates. Decisions on intensification, de-escalation and allografting rely on the ability to divide an apparently homogeneous group according to risk. A wide range of clinical, cytogenetic and molecular variables may be used to inform this task. Cytogenetic and molecular characterisation has already identified subgroups, such as acute promyelocytic leukaemia (APL) with t(15;17)/PML-RARA and AML with FLT3 mutation for which targeted therapies are available, and further molecularly defined groups who may be potential candidates for this approach are likely to be identified in the future. This review examines the range of established clinical and diagnostic parameters that should be used in assessing prognosis for a patient with AML and looks ahead to an expanding repertoire of potential variables that are currently under evaluation.
Topics: Antineoplastic Combined Chemotherapy Protocols; Humans; Leukemia, Myeloid, Acute; Prognosis
PubMed: 21078537
DOI: 10.1016/j.blre.2010.10.002 -
British Journal of Haematology Apr 2014Acute myeloid leukaemia (AML) is a heterogeneous disease. Prognosis of AML is influenced both by patient-specific as well as disease-specific factors. Age is the most... (Review)
Review
Acute myeloid leukaemia (AML) is a heterogeneous disease. Prognosis of AML is influenced both by patient-specific as well as disease-specific factors. Age is the most prominent patient-specific risk factor, while chromosomal aberrations are the strongest disease-specific risk factors. For patients with cytogenetically normal AML, prognosis can be specified by mutational status of the genes NPM1, FLT3 and CEBPA. A growing number of recurrent mutations in additional genes have recently been identified, for which the prognostic effect yet has to be determined. Performance status, geriatric assessment, secondary leukaemia following myelodysplastic syndrome or cytotoxic treatment, common laboratory parameters, leukaemic stem cell frequency, bone marrow microenvironment, gene expression levels, epigenetic changes, micro-RNA's as well as kinetics and depth of response to treatment influence prognosis of AML patients. Despite the high number of established risk factors, only few predictive markers exist which can truly aid therapy decisions in patients with AML.
Topics: Adult; Humans; Leukemia, Myeloid, Acute; Nucleophosmin; Prognosis; Risk Factors
PubMed: 24484469
DOI: 10.1111/bjh.12750 -
British Journal of Cancer Sep 2009MicroRNAs (miRNAs) are short non-coding RNAs that have key functions in a wide array of critical cell processes, including haematopoiesis by regulating the expression of... (Review)
Review
MicroRNAs (miRNAs) are short non-coding RNAs that have key functions in a wide array of critical cell processes, including haematopoiesis by regulating the expression of multiple genes. Aberrant miRNA expression has been described in acute myeloid leukaemia suggesting a role in leukaemogenesis. In this review we summarise the current knowledge.
Topics: Humans; Leukemia, Myeloid, Acute; MicroRNAs; Prognosis
PubMed: 19672257
DOI: 10.1038/sj.bjc.6605232 -
The Lancet. Oncology Jul 2004Acute myeloid leukaemia (AML) is a heterogeneous disease that presents with a range of morphological, cytogenetic, immunophenotypic, and biomolecular features. Over the... (Review)
Review
Acute myeloid leukaemia (AML) is a heterogeneous disease that presents with a range of morphological, cytogenetic, immunophenotypic, and biomolecular features. Over the past 20 years, application of new cytogenetic and molecular techniques has greatly improved knowledge of the pathophysiology of AML, resulting in new potential therapeutic applications. However, the results of current therapy are still unsatisfactory, especially in patients who have adverse prognostic factors at the time of diagnosis. Furthermore, some pivotal questions about the procedures of induction and postinduction therapy of AML remain unanswered, and substantial controversy exists on the optimum therapeutic approach for the disorder.
Topics: Acute Disease; Aged; Antineoplastic Agents; Humans; Leukemia, Myeloid; Middle Aged; Remission Induction; Stem Cell Transplantation; Treatment Outcome
PubMed: 15231251
DOI: 10.1016/S1470-2045(04)01512-8 -
British Journal of Haematology Sep 1999
Review
Topics: Acute Disease; Humans; Leukemia, Myeloid; Recurrence
PubMed: 10519984
DOI: 10.1046/j.1365-2141.1999.01629.x -
Expert Opinion on Biological Therapy Jan 2004Monoclonal antibodies have become an important treatment modality in cancer therapy. Genetically engineered chimaeric and humanised antibodies have demonstrated activity... (Review)
Review
Monoclonal antibodies have become an important treatment modality in cancer therapy. Genetically engineered chimaeric and humanised antibodies have demonstrated activity against a variety of tumours. Whereas the humanised anti-CD33 monoclonal antibody HuM195 has only modest activity against overt acute myeloid leukaemia (AML), it can eliminate minimal residual disease detectable by reverse transcription-polymerase chain reaction in acute promyelocytic leukaemia. High-dose radioimmunotherapy with beta-particle-emitting isotopes targeting CD33, CD45 and CD66 can potentially allow intensification of antileukaemic therapy before bone marrow transplantation. Conversely, alpha-particle immunotherapy with isotopes such as bismuth-213 or actinium-225 offers the possibility of selective tumour cell kill while sparing surrounding normal cells. Targeted chemotherapy with the anti-CD33-calicheamicin construct gemtuzumab ozogamicin has produced remissions as a single agent in patients with relapsed AML and appears promising when used in combination with standard chemotherapy in the treatment of newly diagnosed AML.
Topics: Acute Disease; Animals; Antibodies, Monoclonal; Antineoplastic Combined Chemotherapy Protocols; Humans; Leukemia, Myeloid; Radioimmunotherapy
PubMed: 14680472
DOI: 10.1517/14712598.4.1.95