Acute Myeloid Leukemia Clinical Practice Guidelines in Oncology

2003 ◽  
Vol 1 (4) ◽  
pp. 520 ◽  
Keyword(s):  
Clinical Trials ◽  
Acute Myeloid Leukemia ◽  
Clinical Practice ◽  
Clinical Practice Guidelines ◽  
Practice Guidelines ◽  
Myeloid Leukemia ◽  
Treatment Options ◽  
Innovative Strategies ◽  
Recent Version ◽  
Acute Myeloid

The incidence of leukemia, along with its precursor, myelodysplasia, appears to be rising, particularly in the population over age 60. Recently an expanded panel of clinicians from the NCCN member institutions joined to update guidelines for the treatment of acute myeloid leukemia. Although there are some areas in which clinical trials have led to significant improvements in treatment, for the most part, recent trials have only served to highlight the continued need for innovative strategies to overcome this disease. These guidelines focus on outlining reasonable treatment options based on the information available. For the most recent version of the guidelines, please visit NCCN.org

Acute Myeloid Leukemia Clinical Practice Guidelines in Oncology

2006 ◽  
Vol 4 (1) ◽  
pp. 16 ◽  
Author(s):  
_ _
Keyword(s):  
Clinical Trials ◽  
Acute Myeloid Leukemia ◽  
Clinical Practice ◽  
Young Adulthood ◽  
Older Patients ◽  
Myeloid Leukemia ◽  
Innovative Strategies ◽  
The Past ◽  
Recent Version ◽  
Acute Myeloid

Approximately 11,960 people will be diagnosed with acute myeloid leukemia (AML) in 2005, and 9,000 patients will die of the disease. As the population ages, the incidence of AML, along with myelodysplasia, appears to be rising. Equally disturbing is the increasing incidence of treatment-related myelodysplasia and leukemia in survivors of tumors of childhood and young adulthood such as Hodgkin's disease, sarcomas, breast and testicular cancers, and lymphomas. Recent large clinical trials have highlighted the need for new, innovative strategies because outcomes for AML patients, particularly older patients, have not substantially changed in the past 3 decades. For the most recent version of the guidelines, please visit NCCN.org

scholarly journals Acute Myeloid Leukemia, Version 3.2019, NCCN Clinical Practice Guidelines in Oncology

2019 ◽  
Vol 17 (6) ◽  
pp. 721-749 ◽  
Author(s):  
Martin S. Tallman ◽  
Eunice S. Wang ◽  
Jessica K. Altman ◽  
Frederick R. Appelbaum ◽  
Vijaya Raj Bhatt ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Clinical Practice ◽  
Clinical Practice Guidelines ◽  
Practice Guidelines ◽  
Myeloid Leukemia ◽  
Treatment Options ◽  
The United States ◽  
Nccn Guidelines ◽  
Younger Age ◽  
Acute Myeloid

Acute myeloid leukemia (AML) is the most common form of acute leukemia among adults and accounts for the largest number of annual deaths due to leukemias in the United States. Recent advances have resulted in an expansion of treatment options for AML, especially concerning targeted therapies and low-intensity regimens. This portion of the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for AML focuses on the management of AML and provides recommendations on the workup, diagnostic evaluation and treatment options for younger (age <60 years) and older (age ≥60 years) adult patients.

Acute Myeloid Leukemia

2008 ◽  
Vol 6 (10) ◽  
pp. 962 ◽  
Author(s):  
_ _
Keyword(s):  
Clinical Trials ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Treatment Options ◽  
Significant Treatment ◽  
Innovative Strategies ◽  
Relative Risks ◽  
Polymerase Chain ◽  
Recent Version ◽  
Acute Myeloid

Approximately 13,290 people will be diagnosed with acute myeloid leukemia (AML) in 2008, and 8820 patients will die of the disease. As the population ages, the incidence of AML, along with myelodysplasia, appears to be rising. Clinical trials have led to significant treatment improvements in some areas, primarily acute promyelocytic leukemia. However, recent large clinical trials have highlighted the need for new, innovative strategies, because outcomes for AML patients have not substantially changed in the past 3 decades. The NCCN AML Panel has focused on outlining reasonable treatment options based on recent clinical trials and data from basic science, which may identify new risk factors and treatment approaches. These guidelines attempt to provide a rationale for including several treatment options in some categories, as divergent opinions about the relative risks and benefits of various treatment options have surfaced. Updates for 2009 include new clarifications of some treatment recommendations as well as for defining polymerase chain reaction positivity. For the most recent version of the guidelines, please visit NCCN.org

scholarly journals Acute Myeloid Leukemia, Version 3.2017, NCCN Clinical Practice Guidelines in Oncology

2017 ◽  
Vol 15 (7) ◽  
pp. 926-957 ◽  
Author(s):  
Margaret R. O'Donnell ◽  
Martin S. Tallman ◽  
Camille N. Abboud ◽  
Jessica K. Altman ◽  
Frederick R. Appelbaum ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Clinical Practice ◽  
Clinical Practice Guidelines ◽  
Practice Guidelines ◽  
Myeloid Leukemia ◽  
Acute Myeloid

scholarly journals Personalizing initial therapy in acute myeloid leukemia: incorporating novel agents into clinical practice

2018 ◽  
Vol 9 (5) ◽  
pp. 109-121 ◽  
Author(s):  
Christin B. DeStefano ◽  
Christopher S. Hourigan
Keyword(s):  
Clinical Trials ◽  
Acute Myeloid Leukemia ◽  
Clinical Practice ◽  
Drug Administration ◽  
Myeloid Leukemia ◽  
Initial Therapy ◽  
Gemtuzumab Ozogamicin ◽  
The Past ◽  
Molecular Etiology ◽  
Acute Myeloid

While the past decade has seen a revolution in understanding of the genetic and molecular etiology of the disease, in clinical practice, initial therapy for acute myeloid leukemia (AML) patients has been a relatively straightforward choice between intensive combination cytotoxic induction therapy as used for decades or less-intensive hypomethylating therapy. The year 2017, however, witnessed US Food and Drug Administration approvals of midostaurin, enasidenib, gemtuzumab ozogamicin and CPX-351 for AML patients, with many other promising agents currently in clinical trials. This review discusses these options, highlights unanswered questions regarding optimal combinations and proposes some suggested approaches for the personalization of initial therapy for AML patients.

scholarly journals Duplex Sequencing Accurately Detects Variants below 1/100,000 in Genes Recurrently Mutated in Acute Myeloid Leukemia

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2769-2769
Author(s):  
Jacob E. Higgins ◽  
Lindsey N. Williams ◽  
Sarah A Buckley ◽  
Christopher S. Hourigan ◽  
Jerald P. Radich ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Residual Disease ◽  
Treatment Options ◽  
Surrogate Endpoint ◽  
Dna Duplex ◽  
New Treatments ◽  
Duplex Sequencing ◽  
Acute Myeloid

Abstract Acute myeloid leukemia (AML) is a challenging disease to treat: most patients achieve remission after induction chemotherapy, but the majority eventually relapse. Minimal residual disease (MRD) after initial treatment is the best predictor of relapse and is thus a critical metric around which to develop new treatments. However, conventional MRD diagnostics, including cytology and flow cytometry, are of variable sensitivity and often only perform well in specialty centers, and there is no gold standard. Molecular tests developed to measure trace MRD in other hematological malignancies (i.e. CML) are high-resolution but assay a single, universally-present mutation, while many different genetic drivers exist in AML and these are spread among dozens of genes. Virtually every AML patient harbors a unique combination of mutations, making it difficult to design an effective universal assay. As such, most reported molecular AML MRD assays are either sensitive for mutations that are only found in a narrow subset of patients, or can screen many potential sites of mutation, but with low sensitivity. Here we present a broadly applicable Duplex Sequencing-based AML MRD assay that can readily detect mutant allele frequencies (MAF) below 1/10,000 across a large panel of genes, and below 1/100,000 in a focused panel. Conventional next generation sequencing (NGS) introduces errors during amplification and sequencing, creating a background of artifactual noise that obscures true mutations present below ~1%. Duplex Sequencing improves accuracy >100,000-fold through a molecular tagging approach whereby both strands of each original DNA duplex are ligated with a unique molecular barcode and amplified such that the reads generated from each strand can be related back to their unique original duplex. Reads can also be distinguished from those of their mate strand, thus the two strands of each DNA duplex can be compared and any discrepant nucleotide positions are discounted as errors. Our complete AML panel targets 151 exons or hotspot codons in 29 genes with a 59 kilobase (kb) hybrid-capture footprint. This region comprises loci containing single-nucleotide and short indel mutations found in approximately 90% of adult AMLs. A mean Duplex error-corrected sequence depth of 10,837 and a maximum Duplex depth of 14,967 was obtained across these targets from a single library preparation using 250 ng of sheared leukocyte DNA (Fig. 1). Duplex depth can be readily increased by preparing additional Duplex libraries from the same source DNA to achieve proportionally higher sensitivity for rarer variants. This stands in contrast to conventional NGS where, beyond a modest level, an increase in depth simply increases the number of background errors identified (Fig. 2A). We simulated low-level residual disease by mixing control DNA from a healthy young blood donor with DNA from 9 human cell lines harboring known AML mutations at dilutions from 1:100 to 1:100,000 (Table 2). The genomic loci of these 9 mutations in NRAS, KRAS and TP53 were captured with a small 1 kb probe panel. This mixture was sequenced to a mean Duplex depth of >1,000,000-fold, with the highest and lowest MAFs shown in Fig. 2B. All were close to expected frequencies (r2=0.96) with MAF as low as 6x10-6 (Fig. 3). As proof of specificity, we examined all coding nucleotide positions (excluding the 9 expected variants) and identified only 241 background variant counts out of 414,452,402 total Duplex BP, for an aggregate mutation frequency of 5.8x10-7, consistent with the estimated background of normal human aging. Our Duplex Sequencing-based AML MRD assay is flexible, broadly applicable and extremely sensitive. The assay is easily implemented using standard NGS equipment and automated cloud-based analysis software. The ~90% of AML patients served by this SNV-focused panel can be expanded to nearly 100% with complementary indel detection via targeted NGS RT-PCR. Optionally, when a patient's mutation profile from time-of-diagnosis is known, MRD testing can focus exclusively on those targets using a subset of pre-validated probes to reduce sequencing cost. Improved MRD testing will facilitate accurate prognostication, better selection among treatment options, and could serve as a surrogate endpoint in clinical trials to bring new treatments to patients faster. We are currently evaluating Duplex Sequencing MRD tests in both retrospective and prospective clinical trials. Disclosures Higgins: TwinStrand Biosciences: Employment. Williams:TwinStrand Biosciences: Employment. Buckley:CTI Biopharma: Employment; TwinStrand Biosciences: Consultancy. Radich:TwinStrand Biosciences: Research Funding. Salk:TwinStrand Biosciences: Employment, Equity Ownership.

scholarly journals Core outcome set measurement for future clinical trials in acute myeloid leukemia: the HARMONY study protocol using a multi-stakeholder consensus-based Delphi process and a final consensus meeting

2020 ◽  
Author(s):  
Katharina M Lang ◽  
Kathryn L. Harrison ◽  
Paula R. Williamson ◽  
Brian J.P. Huntly ◽  
Gert Ossenkoppele ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Core Outcome Set ◽  
Core Outcome ◽  
Face To Face ◽  
Outcome Set ◽  
Multi Stakeholder ◽  
Stakeholder Consensus ◽  
Acute Myeloid

Abstract Background Acute myeloid leukemia is the most common acute leukemia in adults with an unacceptably low cure rate. In recent years a number of new treatment strategies and compounds were developed for the treatment of acute myeloid leukemia. There were several randomized, controlled clinical trials with the objective to improve patients’ management and patients’ outcome in acute myeloid leukemia. Unfortunately, these trials are not always directly comparable, as they do not measure the same outcomes and currently there are no core outcome sets that can be utilized to guide outcome selection and harmonization in this disease area. The HARMONY Alliance is a public-private European Network established in 2017, which currently includes 53 partners and 32 associated members from 22 countries. Amongst many other goals of the HARMONY Alliance, Work Package 2 focuses on defining outcomes that are relevant to each hematological malignancy. In accordance, a pilot study will be performed to define core outcome set in acute myeloid leukemia. Methods The pilot study will use a three-round Delphi survey and a final consensus meeting to define a core outcome set. Participants will be recruited from different stakeholder groups, including patients, clinicians, regulators and members of the European Federation of Pharmaceutical Industries and Associations (EFPIA). At the pre-Delphi stage a literature research was conducted followed by several semi-structured interviews of clinical public and private key opinion leaders. Subsequently the preliminary outcome list was discussed in several multi-stakeholder face-to-face meetings. The Delphi survey will reduce the preliminary outcome list to essential core outcomes. After completing the last Delphi round a final face-to-face meeting is planned to achieve consensus about core outcome set in acute myeloid leukemia. Discussion The pilot Delphi as part of HARMONY Alliance aims to define a core outcome set in acute myeloid leukemia based on a multi-stakeholder consensus. Such a core outcome set will help to allow consistent comparison of future clinical trials and real world evidence research and ensures that appropriate outcomes valued by a range of stakeholders are measured within future trials.

scholarly journals Acute Myeloid Leukemia: Advanced Practice Management From Presentation to Cure

2020 ◽  
Vol 11 (8) ◽  
Author(s):  
Meredith Beaton, RN, MSN, AG-ACNP ◽  
Glen J. Peterson, RN, DNP, ACNP ◽  
Kelly O'Brien, RN, MSN, ANP-C, ACNP-BC
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Performance Status ◽  
Treatment Options ◽  
Signs And Symptoms ◽  
The Elderly ◽  
Poor Performance Status ◽  
Curative Therapy ◽  
Initial Symptoms ◽  
Acute Myeloid

Acute myeloid leukemia (AML) is the most common acute leukemia in adults, diagnosed in approximately 21,450 individuals annually in the US with nearly 11,000 deaths attributable to this disease (National Cancer Institute, 2020). Acute myeloid leukemia is a disease of the elderly, with the average age of diagnosis being 68 years old (Kouchkovsky & Abdul-Hay, 2016). It is a heterogeneous disease with widely varying presentations but universally carries a poor prognosis in the majority of those affected. Unfortunately, the 5-year overall survival rate remains poor, at less than 5% in patients over 65 years of age (Thein, Ershler, Jemal, Yates, & Baer, 2013). The landscape of AML is beginning to change, however, as new and improved treatments are emerging. Advanced practitioners (APs) are often involved in the care of these complex patients from the time of initial symptoms through diagnosis, treatment, and potentially curative therapy. It is vitally important for APs to understand and be aware of the various presentations, initial management strategies, diagnostic workup, and treatment options for patients with AML, especially in the elderly population, which until recently had few treatment options. This Grand Rounds article highlights the common presenting signs and symptoms of patients with AML in the hospital, including a discussion of the upfront clinical stability issues, oncologic emergencies, diagnostic evaluation, and current treatment options for elderly patients and those with poor performance status.

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