scholarly journals Management of Acute Myeloid Leukemia: Current Treatment Options and Future Perspectives

Cancers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 5722
Author(s):  
Maximilian Fleischmann ◽  
Ulf Schnetzke ◽  
Andreas Hochhaus ◽  
Sebastian Scholl
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Current Treatment ◽  
Current Status ◽  
Epigenetic Therapy ◽  
Comprehensive Overview ◽  
Secondary Resistance ◽  
Acute Myeloid

Treatment of acute myeloid leukemia (AML) has improved in recent years and several new therapeutic options have been approved. Most of them include mutation-specific approaches (e.g., gilteritinib for AML patients with activating FLT3 mutations), or are restricted to such defined AML subgroups, such as AML-MRC (AML with myeloid-related changes) or therapy-related AML (CPX-351). With this review, we aim to present a comprehensive overview of current AML therapy according to the evolved spectrum of recently approved treatment strategies. We address several aspects of combined epigenetic therapy with the BCL-2 inhibitor venetoclax and provide insight into mechanisms of resistance towards venetoclax-based regimens, and how primary or secondary resistance might be circumvented. Furthermore, a detailed overview on the current status of AML immunotherapy, describing promising concepts, is provided. This review focuses on clinically important aspects of current and future concepts of AML treatment, but will also present the molecular background of distinct targeted therapies, to understand the development and challenges of clinical trials ongoing in AML patients.

scholarly journals Acute Myeloid Leukemia: Aging and Epigenetics

Cancers ◽  
2019 ◽  
Vol 12 (1) ◽  
pp. 103 ◽  
Author(s):  
Polina Zjablovskaja ◽  
Maria Carolina Florian
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Treatment Options ◽  
The Elderly ◽  
Current Treatment ◽  
Cellular Aging ◽  
Specific Cell ◽  
Poor Overall Survival ◽  
Hematological Disorders ◽  
Acute Myeloid

Acute myeloid leukemia (AML) is an aggressive hematological disorder mainly affecting people of older age. AML initiation is primarily attributed to mutations in crucial cellular regulators such as epigenetic factors, transcription factors, and signaling genes. AML’s aggressiveness and responsiveness to treatment depends on the specific cell type where leukemia first arose. Aged hematopoietic cells are often genetically and/or epigenetically altered and, therefore, present with a completely different cellular context for AML development compared to young cells. In this review, we summarize key aspects of AML development, and we focus, in particular, on the contribution of cellular aging to leukemogenesis and on current treatment options for elderly AML patients. Hematological disorders and leukemia grow exponentially with age. So far, with conventional induction therapy, many elderly patients experience a very poor overall survival rate requiring substantial social and medical costs during the relatively few remaining months of life. The global population’s age is increasing rapidly without an acceptable equal growth in therapeutic management of AML in the elderly; this is in sharp contrast to the increase in successful therapies for leukemia in younger patients. Therefore, a focus on the understanding of the biology of aging in the hematopoietic system, the development of appropriate research models, and new therapeutic approaches are urged.

More Versus Less Therapy for Older Adults With Acute Myeloid Leukemia: New Perspectives on an Old Debate

2019 ◽  
pp. 421-432 ◽  
Author(s):  
Heidi D. Klepin ◽  
Elihu Estey ◽  
Tapan Kadia
Keyword(s):  
Older Adults ◽  
Decision Making ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Treatment Decision ◽  
Important Conclusion ◽  
Treatment Decision Making ◽  
Acute Myeloid

Most patients with newly diagnosed acute myeloid leukemia (AML) are at least age 65 and continue to have short survival, with many patients receiving no specific anti-AML therapy, particularly if they are older than age 75. Although consensus regarding optimal treatment of this growing population is lacking, treatment options are expanding even for the oldest patients. A fundamental question when seeing an older patient with AML is whether to recommend “more intensive” or “less intensive” induction therapy. Existing data can support more intensive treatment strategies for selected older adults, although there is growing evidence to support less intensive therapies as well. Randomized trials to provide clear comparisons between treatment strategies among well-characterized older adult populations are lacking. Reliance on age alone to determine treatment choice is problematic, as “fitness” or “unfitness” varies dramatically among patients of the same chronologic age and remains poorly characterized in existing studies. This article will provide differing perspectives on the “more” versus “less” question, with particular attention to recent drug approvals. Issues relevant to both treatment decision-making in practice and alternative trial design to inform gaps in knowledge will be discussed. Given the heterogeneity, an important conclusion will be that there is unlikely to be a single best approach and that appropriate decision-making requires considerations of many factors specific to individual patients.

scholarly journals Strategizing the Treatment Approach to Acute Myeloid Leukemia

2021 ◽  
pp. 1-6
Author(s):  
Laura Finn ◽  
Michael Lunski ◽  
Saikrishna Gadde ◽  
Matthew Alberti ◽  
Danny Markabawi ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Molecular Classification ◽  
Ongoing Research ◽  
Molecular Alterations ◽  
Treatment Regimens ◽  
New Treatments ◽  
Acute Myeloid

For decades acute myeloid leukemia, the primary acute leukemia affecting adults, had limited treatment options. Since 2017, we have seen discovery and development in cytogenetic and molecular classification of acute myeloid leukemia, improved understanding of cell signaling pathways, and development of new treatment for acute myeloid leukemia. These new treatments include novel combinations of agents and therapy targeting molecular alterations improving rates of remission and overall survival. Treatment discovery provides therapeutic opportunity to older patients and populations previously excluded from intense induction chemotherapy. In this review, we discuss the timing of first therapy, non-intense treatment regimens achieving remission, and new targets for directed therapy. We reference key clinical trials to expand our discussion of newly approved agents for acute myeloid leukemia. In this review, we highlight the discovery of treatment strategies to improve patient outcomes and ongoing research in leukemia.

scholarly journals Clinical Applications of MicroRNAs in Acute Myeloid Leukemia: A Mini-Review

2021 ◽  
Vol 11 ◽  
Author(s):  
Bhavana Bhatnagar ◽  
Ramiro Garzon
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Treatment Strategies ◽  
Current Treatment ◽  
Clinical Applications ◽  
Response To Therapy ◽  
Medical Decision ◽  
Cellular Processes ◽  
Novel Therapeutic Strategies ◽  
Acute Myeloid

MicroRNAs (miRs) are short non-coding RNAs, typically 18-25 nucleotides in length, that are critically important, through their direct effects on target mRNAs, in a variety of cellular processes including cell differentiation, proliferation and survival. Dysregulated miR expression has been identified in numerous cancer types including acute myeloid leukemia (AML). From a clinical standpoint, several miRs have been shown to associate with prognosis in AML patients. Furthermore, they also carry the potential to be used as biomarkers and to inform medical decision making. In addition, several preclinical studies have provided strong rationale to develop novel therapeutic strategies to target miRs in AML. This review will focus on potential clinical applications of miRs in adult AML and will discuss unique miR signatures in specific AML subtypes, their role in prognostication and response to therapy, as well as miRs that are promising therapeutic targets and ongoing clinical trials directed towards targeting clinically relevant miRs in AML that could allow for improvements in current treatment strategies.

Novel Approaches to the Treatment of Acute Myeloid Leukemia

Hematology ◽  
2011 ◽  
Vol 2011 (1) ◽  
pp. 43-50 ◽  
Author(s):  
Gail J. Roboz
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Residual Disease ◽  
Molecular Genetic ◽  
Treatment Strategies ◽  
Standard Of Care ◽  
The United States ◽  
Current Treatment ◽  
Treatment Standards ◽  
Acute Myeloid

Abstract Approximately 12 000 adults are diagnosed with acute myeloid leukemia (AML) in the United States annually, the majority of whom die from their disease. The mainstay of initial treatment, cytosine arabinoside (ara-C) combined with an anthracycline, was developed nearly 40 years ago and remains the worldwide standard of care. Advances in genomics technologies have identified AML as a genetically heterogeneous disease, and many patients can now be categorized into clinicopathologic subgroups on the basis of their underlying molecular genetic defects. It is hoped that enhanced specificity of diagnostic classification will result in more effective application of targeted agents and the ability to create individualized treatment strategies. This review describes the current treatment standards for induction, consolidation, and stem cell transplantation; special considerations in the management of older AML patients; novel agents; emerging data on the detection and management of minimal residual disease (MRD); and strategies to improve the design and implementation of AML clinical trials.

Treatment Strategies for Therapy-related Acute Myeloid Leukemia

2020 ◽  
Vol 20 (3) ◽  
pp. 147-155 ◽  
Author(s):  
Prajwal Dhakal ◽  
Bimatshu Pyakuryal ◽  
Prasun Pudasainee ◽  
Venkat Rajasurya ◽  
Krishna Gundabolu ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Treatment Strategies ◽  
Acute Myeloid

scholarly journals Minimal residual disease eradication with epigenetic therapy in core binding factor acute myeloid leukemia

2017 ◽  
Vol 92 (9) ◽  
pp. 845-850 ◽  
Author(s):  
Brittany Knick Ragon ◽  
Naval Daver ◽  
Guillermo Garcia-Manero ◽  
Farhad Ravandi ◽  
Jorge Cortes ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Minimal Residual Disease ◽  
Myeloid Leukemia ◽  
Residual Disease ◽  
Epigenetic Therapy ◽  
Core Binding Factor ◽  
Disease Eradication ◽  
Binding Factor ◽  
Minimal Residual ◽  
Acute Myeloid

Molecular determinants of therapy response of venetoclax-based combinations in acute myeloid leukemia

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Philipp Makowka ◽  
Verena Stolp ◽  
Karoline Stoschek ◽  
Hubert Serve
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Current Knowledge ◽  
Therapy Response ◽  
Secondary Resistance ◽  
Molecular Alterations ◽  
Molecular Features ◽  
Slow Progress ◽  
Molecular Aberrations ◽  
Acute Myeloid

Abstract Acute myeloid leukemia (AML) is a heterogeneous, highly malignant disease of the bone marrow. After decades of slow progress, recent years saw a surge of novel agents for its treatment. The most recent advancement is the registration of the Bcl-2 inhibitor ventoclax in combination with a hypomethylating agent (HMA) in the US and Europe for AML patients not eligible for intensive chemotherapy. Treatment of newly diagnosed AML patients with this combination results in remission rates that so far could only be achieved with intensive treatment. However, not all AML patients respond equally well, and some patients relapse early, while other patients experience longer periods of complete remission. A hallmark of AML is its remarkable genetic, molecular and clinical heterogeneity. Here, we review the current knowledge about molecular features of AML that help estimate the probability of response to venetoclax-containing therapies. In contrast to other newly developed AML therapies that target specific recurrent molecular alterations, it seems so far that responses are not specific for a certain subgroup. One exception is spliceosome mutations, where good response has been observed in clinical trials with venetoclax/azacitidine. These mutations are rather associated with a more unfavorable outcome with chemotherapy. In summary, venetoclax in combination with hypomethylating agents represents a significant novel option for AML patients with various molecular aberrations. Mechanisms of primary and secondary resistance seem to overlap with those towards chemotherapy.

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