TARGET: Acute Myeloid Leukemia (AML)
Ontology highlight
ABSTRACT:
SECONDARY ACCESSION(S): PRJNA89525
REPOSITORIES: dbGaP
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Project description:Despite expanding knowledge in the molecular landscape of acute myeloid leukemia (AML) and an increasing understanding of leukemogenic pathways, little has changed in the treatment of AML in the last 40 years. Since introduction in the 1970s, combination chemotherapy consisting of anthracycline and cytarabine has been the mainstay of treatment, with major therapeutic advances based on improving supportive care rather than the introduction of novel therapeutics. Over the last decades, there have been extensive efforts to identify specific target mutations or pathways with the aim of improving clinical outcomes. Finally, after a prolonged wait, we are witnessing the next wave of AML treatment, characterized by a more "precise" and "personalized" understanding of the unique molecular or genetic mapping of individual patients. This new trend has since been further facilitated, with four new FDA approvals granted in 2017 in AML therapeutics. Currently, a total of eight targeted agents have been approved since 2017 (as of Jan. 2020). In this review, we will briefly discuss these newer agents in the context of their indication and the basis of their approval.
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2004-02-25 | E-GEOD-1065 | biostudies-arrayexpress
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2004-02-25 | E-GEOD-1066 | biostudies-arrayexpress
Project description:Purpose of reviewThe acute myeloid leukemia (AML) treatment landscape has rapidly evolved over the past few years. These changes have several implications for the care of older adults (≥ 60 years), who have inferior clinical outcomes. We review decision-making in older adults, focusing on patient- and disease-related factors. We then summarize current treatment options, including multiple recently approved therapies, based on hypothetical clinical scenarios.Recent findingsIn lieu of using chronological age to determine fitness, we highlight the importance of standardized fitness assessments using geriatric assessments. Next, we review intensive and lower-intensity treatment options in the upfront setting. We focus on multiple newly approved medications, including venetoclax, midostaurin, CPX-351, gemtuzumab, glasdegib, enasidenib, and ivosidenib, and their specific indications. Lastly, we briefly discuss supportive care of older adults with AML. Outcomes of older adults with AML remain poor; fortunately, there are many new promising treatment options. Personalized treatment plans based on patient- and disease-specific factors are essential to the care of older adults with AML.
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Project description:Equal access to clinical trial enrollment is important to ensure that findings are generalizable to the broader population. This study aimed to evaluate disparities in enrollment on pediatric oncology clinical trials. We assessed the relationship between patient characteristics and enrollment on COG trial AAML1031 in a cohort of pediatric patients with AML in the Pediatric Health Information System. The associations of enrollment with outcomes were evaluated. Non-Hispanic Black patients, infants, and patients from zip codes with a lower proportion of poverty were less likely to enroll (30% vs. 61%, p = .004; 34% vs. 58%, p = .003; 46% vs. 58%, p = .02). On-therapy mortality was similar among enrolled and nonenrolled patients (7.3% vs. 8.9%, p = .47). Differences in early mortality were more pronounced among nonenrolled patients compared to enrolled patients (3.0% vs. 0.5%, p = .03). Understanding the etiology of these disparities will inform strategies to ensure balanced access to clinical trials across patient populations.
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2004-02-26 | GSE1066 | GEO
Project description:[Submitter has not provided a description of the experiment] Keywords: other
2004-02-26 | GSE1065 | GEO
Project description:Late relapse, defined as relapse arising after at least 5 years of remission, is rare and occurs in 1-3% of patients with acute myeloid leukemia (AML). The underlying mechanisms of late relapse remain poorly understood. We identified patients with AML who achieved remission with standard induction chemotherapy and relapsed after at least five years of remission (n = 15). Whole exome sequencing was performed in available bone marrow samples obtained at diagnosis (n = 10), remission (n = 6), and first relapse (n = 10). A total of 41 driver mutations were identified, of which 11 were primary tumor-specific, 17 relapse-specific, and 13 shared (detected both in primary and relapsed tumor samples). We demonstrated that 12 of 13 shared mutations were in epigenetic modifier and spliceosome genes. Longitudinal genomic characterization revealed that in eight of 10 patients the founder leukemic clone persisted after chemotherapy and established the basis of relapse years later. Understanding the mechanisms of such quiescence in leukemic cells may help designing future strategies aimed at increasing remission duration in patients with AML.
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Project description:Acute lymphoblast leukemia (ALL) is characterized by overproduction of immature white blood cells in the bone marrow. ALL is most common in the childhood and has high (>80%) cure rate. In contrast, acute myeloid leukemia (AML) has far greater mortality rate than the ALL and is most commonly affecting older adults. However, AML is a leading cause of childhood cancer mortality. In this study, we compare gene expression and molecular pathway activation patterns in three normal blood, seven pediatric ALL and seven pediatric AML bone marrow samples. We identified 172/94 and 148/31 characteristic gene expression/pathway activation signatures, clearly distinguishing pediatric ALL and AML cells, respectively, from the normal blood. The pediatric AML and ALL cells differed by 139/34 gene expression/pathway activation biomarkers. For the adult 30 AML and 17 normal blood samples, we found 132/33 gene expression/pathway AML-specific features, of which only 7/2 were common for the adult and pediatric AML and, therefore, age-independent. At the pathway level, we found more differences than similarities between the adult and pediatric forms. These findings suggest that the adult and pediatric AMLs may require different treatment strategies.
| S-EPMC5182073 | biostudies-literature
Project description:Acute myeloid leukemia (AML) is a heterogenous and complex disease characterized by rapid cellular proliferation, an aggressive clinical course, and generally high mortality. While progress has been made in the understanding of the genetic and molecular biology of the disease, the standard of care for patients had only changed minimally over the past 40 years. Recently, rapid movement of potentially useful agents from bench to bedside has translated into new therapies either recently approved or in clinical trials. These therapies include improved chemotherapies, mutationally targeted inhibitors, pro-apoptotic agents, microenvironment targeting molecules, cell cycle checkpoint inhibitors, and epigenetic regulators. Furthermore, advances in immunotherapy employ monoclonal and bispecific antibodies, chimeric antigen receptor (CAR) T cells, checkpoint inhibitors, and vaccines provide an alternative pathway for AML treatment. In this review, we discuss the recent results of completed or ongoing clinical trials with these novel therapeutic agents in AML.
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