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1.
Animals (Basel) ; 13(21)2023 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-37958113

RESUMO

As precision livestock farming (PLF) technologies emerge, it is important to consider their social and ethical dimensions. Reviews of PLF have highlighted the importance of considering ethical issues related to privacy, security, and welfare. However, little attention has been paid to ethical issues related to transparency regarding these technologies. This paper proposes a framework for developing responsible transparency in the context of PLF. It examines the kinds of information that could be ethically important to disclose about these technologies, the different audiences that might care about this information, the challenges involved in achieving transparency for these audiences, and some promising strategies for addressing these challenges. For example, with respect to the information to be disclosed, efforts to foster transparency could focus on: (1) information about the goals and priorities of those developing PLF systems; (2) details about how the systems operate; (3) information about implicit values that could be embedded in the systems; and/or (4) characteristics of the machine learning algorithms often incorporated into these systems. In many cases, this information is likely to be difficult to obtain or communicate meaningfully to relevant audiences (e.g., farmers, consumers, industry, and/or regulators). Some of the potential steps for addressing these challenges include fostering collaborations between the developers and users of PLF systems, developing techniques for identifying and disclosing important forms of information, and pursuing forms of PLF that can be responsibly employed with less transparency. Given the complexity of transparency and its ethical and practical importance, a framework for developing and evaluating transparency will be an important element of ongoing PLF research.

2.
J Gen Philos Sci ; 54(2): 259-286, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36843654

RESUMO

In recent years, many philosophers of science have rejected the "value-free ideal" for science, arguing that non-epistemic values have a legitimate role to play in scientific inquiry. However, this philosophical position raises the question of how to distinguish between legitimate and illegitimate influences of values in science. In this paper, we argue that those seeking to address this "new" demarcation problem can benefit by drawing lessons from the "old" demarcation problem, in which philosophers tried to find a way of distinguishing between science and non-science. Many of those who worked on this problem ultimately found that efforts to provide necessary and sufficient conditions for defining science failed, and most concluded that the best solution to the problem was to characterize scientific hypotheses, theories, and research programs in terms of some common norms. We suggest that those seeking to distinguish between legitimate and illegitimate value influences on science would do well to adopt a similar approach. Rather than attempting to establish necessary and sufficient conditions for identifying appropriate value influences, it will be more fruitful to evaluate scientific activities based on their adherence to a set of epistemic and ethical norms that can be implemented in scientific practice by means of rules, conventions, policies, and procedures.

3.
Account Res ; : 1-25, 2022 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-36288536

RESUMO

Authorship of academic publications is central to scientists' careers, but decisions about how to include and order authors on publications are often fraught with difficult ethical issues. To better understand scholars' experiences with authorship, we developed a novel concept, authorship climate, which assesses perceptions of the procedural, informational, and distributive justice associated with authorship decisions. We conducted a representative survey of more than 3,000 doctoral students, postdoctoral researchers, and assistant professors from a stratified random sample of U.S. biology, economics, physics, and psychology departments. We found that individuals who tend to have more power on science teams perceived authorship climate to be more positive than those who tend to have less power. Alphabetical approaches for assigning authorship were associated with higher perceptions of procedural justice and informational justice but lower perceptions of distributive justice. Individuals with more marginalized identities also tended to perceive authorship climate more negatively than those with no marginalized identities. These results illustrate how the concept of authorship climate can facilitate enhanced understanding of early-career scholars' authorship experiences, and they highlight potential steps that can be taken to promote more positive authorship experiences for scholars of all identities.

4.
PLoS One ; 17(9): e0274278, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36099241

RESUMO

Early research on the impact of COVID-19 on academic scientists suggests that disruptions to research, teaching, and daily work life are not experienced equally. However, this work has overwhelmingly focused on experiences of women and parents, with limited attention to the disproportionate impact on academic work by race, disability status, sexual identity, first-generation status, and academic career stage. Using a stratified random survey sample of early-career academics in four science disciplines (N = 3,277), we investigated socio-demographic and career stage differences in the effect of the COVID-19 pandemic along seven work outcomes: changes in four work areas (research progress, workload, concern about career advancement, support from mentors) and work disruptions due to three COVID-19 related life challenges (physical health, mental health, and caretaking). Our analyses examined patterns across career stages as well as separately for doctoral students and for postdocs/assistant professors. Overall, our results indicate that scientists from marginalized (i.e., devalued) and minoritized (i.e., underrepresented) groups across early career stages reported more negative work outcomes as a result of COVID-19. However, there were notable patterns of differences depending on the socio-demographic identities examined. Those with a physical or mental disability were negatively impacted on all seven work outcomes. Women, primary caregivers, underrepresented racial minorities, sexual minorities, and first-generation scholars reported more negative experiences across several outcomes such as increased disruptions due to physical health symptoms and additional caretaking compared to more privileged counterparts. Doctoral students reported more work disruptions from life challenges than other early-career scholars, especially those related to health problems, while assistant professors reported more negative changes in areas such as decreased research progress and increased workload. These findings suggest that the COVID-19 pandemic has disproportionately harmed work outcomes for minoritized and marginalized early-career scholars. Institutional interventions are required to address these inequalities in an effort to retain diverse cohorts in academic science.


Assuntos
COVID-19 , Médicos , COVID-19/epidemiologia , Feminino , Humanos , Mentores , Pandemias , Pesquisadores
5.
Stud Hist Philos Sci ; 88: 1-9, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33945897

RESUMO

Both philosophers and scientists have recently promoted transparency as an important element of responsible scientific practice. Philosophers have placed particular emphasis on the ways that transparency can assist with efforts to manage value judgments in science responsibly. This paper examines a potential challenge to this approach, namely, that efforts to promote transparency can themselves be value-laden. This is particularly problematic when transparency incorporates second-order value judgments that are underwritten by the same values at stake in the desire for transparency about the first-order value judgments involved in scientific research. The paper uses a case study involving research on Lyme disease to illustrate this worry, but it responds by elucidating a range of scenarios in which transparency can still play an effective role in managing value judgments responsibly.


Assuntos
Doença de Lyme , Coleta de Dados , Humanos , Doença de Lyme/diagnóstico , Doença de Lyme/terapia
6.
Integr Environ Assess Manag ; 17(6): 1229-1242, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33913617

RESUMO

A possible way to alleviate the public skepticism toward regulatory science is to increase transparency by making all data and value judgments used in regulatory decision making accessible for public interpretation, ideally early on in the process, and following the concepts of Open Science. This paper discusses the opportunities and challenges in strengthening Open Science initiatives in regulatory environmental risk assessment (ERA). In this discussion paper, we argue that the benefits associated with Open Science in regulatory ERA far outweigh its perceived risks. All stakeholders involved in regulatory ERA (e.g., governmental regulatory authorities, private sector, academia, and nongovernmental organizations), as well as professional organizations like the Society of Environmental Toxicology and Chemistry, can play a key role in supporting the Open Science initiative, by promoting the use of recommended reporting criteria for reliability and relevance of data and tools used in ERA, and by developing a communication strategy for both professionals and nonprofessionals to transparently explain the socioeconomic value judgments and scientific principles underlying regulatory ERA. Integr Environ Assess Manag 2021;17:1229-1242. © 2021 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).


Assuntos
Comunicação , Ecotoxicologia , Monitoramento Ambiental , Reprodutibilidade dos Testes , Medição de Risco
7.
Sci Transl Med ; 12(526)2020 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-31941826

RESUMO

Clonal hematopoiesis is associated with various age-related morbidities. Error-corrected sequencing (ECS) of human blood samples, with a limit of detection of ≥0.0001, has demonstrated that nearly every healthy individual >50 years old harbors rare hematopoietic clones below the detection limit of standard high-throughput sequencing. If these rare mutations confer survival or proliferation advantages, then the clone(s) could expand after a selective pressure such as chemotherapy, radiotherapy, or chronic immunosuppression. Given these observations and the lack of quantitative data regarding clonal hematopoiesis in adolescents and young adults, who are more likely to serve as unrelated hematopoietic stem cell donors, we completed this pilot study to determine whether younger adults harbored hematopoietic clones with pathogenic mutations, how often those clones were transferred to recipients, and what happened to these clones over time after transplantation. We performed ECS on 125 blood and marrow samples from 25 matched unrelated donors and recipients. Clonal mutations, with a median variant allele frequency of 0.00247, were found in 11 donors (44%; median, 36 years old). Of the mutated clones, 84.2% of mutations were predicted to be molecularly pathogenic and 100% engrafted in recipients. Recipients also demonstrated de novo clonal expansion within the first 100 days after hematopoietic stem cell transplant (HSCT). Given this pilot demonstration that rare, pathogenic clonal mutations are far more prevalent in younger adults than previously appreciated, and they engraft in recipients and persist over time, larger studies with longer follow-up are necessary to correlate clonal engraftment with post-HSCT morbidity.


Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Mutação/genética , Adulto , Feminino , Doença Enxerto-Hospedeiro , Humanos , Masculino , Pessoa de Meia-Idade , Mutação de Sentido Incorreto , Projetos Piloto
9.
Environ Health Perspect ; 127(12): 125002, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31834829

RESUMO

BACKGROUND: Numerous types of rapid toxicity or exposure assays and platforms are providing information relevant to human hazard and exposure identification. They offer the promise of aiding decision-making in a variety of contexts including the regulatory management of chemicals, evaluation of products and environmental media, and emergency response. There is a need to consider both the scientific validity of the new methods and the values applied to a given decision using this new information to ensure that the new methods are employed in ways that enhance public health and environmental protection. In 2018, a National Academies of Sciences, Engineering, and Medicine (NASEM) workshop examined both the toxicological and societal aspects of this challenge. OBJECTIVES: Our objectives were to explore the challenges of adopting new data streams into regulatory decision-making and highlight the need to align new methods with the information and confidence needs of the decision contexts in which the data may be applied. METHODS: We go beyond the NASEM workshop to further explore the requirements of different decision contexts. We also call for the new methods to be applied in a manner consistent with the core values of public health and environmental protection. We use the case examples presented in the NASEM workshop to illustrate a range of decision contexts that have applied or could benefit from these new data streams. Organizers of the NASEM workshop came together to further evaluate the main themes from the workshop and develop a joint assessment of the critical needs for improved use of emerging toxicology tools in decision-making. We have drawn from our own experience and individual decision or research contexts as well as from the case studies and panel discussions from the workshop to inform our assessment. DISCUSSION: Many of the statutes that regulate chemicals in the environment place a high priority on the protection of public health and the environment. Moving away from the sole reliance on traditional approaches and information sources used in hazard, exposure, and risk assessment, toward the more expansive use of rapidly acquired chemical information via in vitro, in silico, and targeted testing strategies will require careful consideration of the information needed and values considerations associated with a particular decision. In this commentary, we explore the ability and feasibility of using emerging data streams, particularly those that allow for the rapid testing of a large number of chemicals across numerous biological targets, to shift the chemical testing paradigm to one in which potentially harmful chemicals are more rapidly identified, prioritized, and addressed. Such a paradigm shift could ultimately save financial and natural resources while ensuring and preserving the protection of public health. https://doi.org/10.1289/EHP4745.


Assuntos
Saúde Ambiental , Toxicologia/métodos , Simulação por Computador , Tomada de Decisões , Exposição Ambiental , Humanos , Saúde Pública , Medição de Risco
10.
Stud Hist Philos Sci ; 75: 1-11, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31426942

RESUMO

Throughout much of the 20th century, philosophers of science maintained a position known as the value-free ideal, which holds that non-epistemic (e.g., moral, social, political, or economic) values should not influence the evaluation and acceptance of scientific results. In the last few decades, many philosophers of science have rejected this position by arguing that non-epistemic values can and should play an important role in scientific judgment and decision-making in a variety of contexts, including the evaluation and acceptance of scientific results. Rejecting the value-free ideal creates some new and vexing problems, however. One of these is that relinquishing this philosophical doctrine may undermine the integrity of scientific research if practicing scientists decide to allow non-epistemic values to impact their judgment and decision-making. A number of prominent philosophers of science have sought to show how one can reject the value-free ideal without compromising the integrity of scientific research. In this paper, we examine and critique their views and offer our own proposal for protecting and promoting scientific integrity. We argue that the literature on research ethics and its focus on adherence to norms, rules, policies, and procedures that together promote the aims of science can provide a promising foundation for building an account of scientific integrity. These norms, rules, policies, and procedures provide a level of specificity that is lacking in most philosophical discussions of science and values, and they suggest an important set of tasks for those working in science and values-namely, assessing, justifying, and prioritizing them. Thus, we argue that bringing together the literature on research ethics with the literature on science and values will enrich both areas and generate a more sophisticated and detailed account of scientific integrity.


Assuntos
Ética em Pesquisa , Filosofia , Projetos de Pesquisa , Valores Sociais , Conhecimento
11.
PLoS One ; 14(7): e0219196, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31318891

RESUMO

Scientific research-especially high-impact research-is increasingly being performed in teams that are interdisciplinary and demographically diverse. Nevertheless, very little research has investigated how the climate on these diverse science teams affects data sharing or the experiences of their members. To address these gaps, we conducted a quantitative study of 266 scientists from 105 NSF-funded interdisciplinary environmental science teams. We examined how team climate mediates the associations between team diversity and three outcomes: satisfaction with the team, satisfaction with authorship practices, and perceptions of the frequency of data sharing. Using path analyses, we found that individuals from underrepresented groups perceived team climate more negatively, which was associated with lower satisfaction with the team and more negative perceptions of authorship practices and data sharing on the team. However, individuals on teams with more demographic diversity reported a more positive climate than those on teams with less demographic diversity. These results highlight the importance of team climate, the value of diverse teams for team climate, and barriers to the full inclusion and support of individuals from underrepresented groups in interdisciplinary science teams.


Assuntos
Diversidade Cultural , Disseminação de Informação , Pesquisa Interdisciplinar , Satisfação Pessoal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários
12.
Environ Health Perspect ; 127(7): 75002, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31353949

RESUMO

BACKGROUND: The open science movement is transforming scientific practice with the goal of enhancing the transparency, productivity, and reproducibility of research. Nevertheless, transparency is a complex concept, and efforts to promote some forms of transparency may do relatively little to advance other important forms of transparency. OBJECTIVES: Drawing from the literature in history, philosophy, and sociology of science, we aim to distinguish between different forms of scientific transparency. Our goal is to identify strategies for achieving forms of transparency that are relevant not only to scientists but also to decision makers and members of the public. DISCUSSION: We draw a distinction between "scientifically relevant transparency" and "socially relevant transparency." Most of the prominent strategies associated with the open science movement (e.g., making data publicly available and registering studies) are designed primarily to promote scientifically relevant transparency. To achieve socially relevant transparency, which is particularly important in fields like environmental health, further steps are needed to provide scientific information in ways that are relevant to decision makers and members of the public. CONCLUSIONS: Promoting socially relevant transparency will require a range of activities by many different individuals and institutions. We propose an array of strategies that can be pursued by scientists and other scholars, journals, universities, funders, government agencies, and members of the public. https://doi.org/10.1289/EHP4808.


Assuntos
Coleta de Dados/métodos , Projetos de Pesquisa/normas , Tomada de Decisões , Humanos
13.
Narrat Inq Bioeth ; 9(1): 47-52, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31031290

RESUMO

The narratives in this issue suggest six themes that merit further exploration: (1) the complexity of citizen science as a concept; (2) the potential to incorporate insights from the literature on team science; (3) the role of power and privilege in citizen science; (4) tensions over standardization, regulation, and quality control; (5) the nature and importance of local knowledge; and (6) the role of funding sources in citizen science initiatives. Taken together, these narratives and themes provide an image of citizen science that is like a kaleidoscope. They portray citizen science as a jumble of different kinds of activities that are in a constant state of flux. One of the most important tasks for the citizen science community going forward is to find ways to harness this energy and innovation while providing appropriate guidelines and standards.


Assuntos
Ciência do Cidadão/ética , Ciência do Cidadão/economia , Ciência do Cidadão/normas , Ética em Pesquisa , Humanos , Pesquisa Interdisciplinar/normas , Poder Psicológico , Competência Profissional/normas , Controle de Qualidade , Apoio à Pesquisa como Assunto
14.
Sci Eng Ethics ; 25(3): 707-718, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-29488061

RESUMO

Researchers have used drones to track wildlife populations, monitor forest fires, map glaciers, and measure air pollution but have only begun to consider how to use these unmanned aerial vehicles to study human beings. The potential use of drones to study public gatherings or other human activities raises novel issues of privacy, confidentiality, and consent, which this article explores in depth. It argues that drone research could fall into several different categories: non-human subjects research (HSR), exempt HSR, or non-exempt HSR. In the case of non-exempt HSR, it will be difficult for institutional review boards to approve studies unless they are designed so that informed consent can be waived. Whether drone research is non-HSR, exempt HSR, or non-exempt HSR, it is important for investigators to consult communities which could be affected by the research.


Assuntos
Aeronaves , Confidencialidade , Coleta de Dados/ética , Ética em Pesquisa , Consentimento Livre e Esclarecido , Privacidade , Sujeitos da Pesquisa/legislação & jurisprudência , Coleta de Dados/legislação & jurisprudência , Comitês de Ética em Pesquisa , Humanos , Vigilância da População , Características de Residência
16.
EFSA J ; 17(Suppl 1): e170707, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32626444

RESUMO

The interplay between science, risk assessment and risk management has always been complex, and even more so in a world increasingly characterised by rapid technical innovation, new modes of communication, suspicion about authorities and experts, and demands for people to have a say in decisions that are made on their behalf. In this challenging era where scientific advice on food safety has never been in greater demand, risk managers should effectively navigate the interplay between facts and values and be able to rely on robust and fit-for-purpose risk assessments to aid them. The fact that societal resistance is often encountered when scientific advice on food safety operates at a distance from social values and fails to actively engage with citizens, has led to increasing emphasis on the need to advance forms of risk assessment that are more contextual, and socially sound and accountable. EFSA's third Scientific Conference explored how risk assessments could be constructed to most usefully meet society's needs and thus connect science with society, while remaining scientifically robust. Contributors to the conference highlighted the need to: (1) frame risk assessments by clear policy goals and decision-making criteria; (2) begin risk assessments with an explicit problem formulation to identify relevant information; (3) make use of reliable risk assessment studies; (4) be explicit about value judgements; (5) address and communicate scientific uncertainty; (6) follow trustworthy processes; (7) publish the evidence and data, and report the way in which they are used in a transparent manner; (8) ensure effective communication throughout the risk analysis process; (9) involve society, as appropriate; and (10) weigh risks and benefits on request. Implementation of these recommendations would contribute to increased credibility and trustworthiness of food safety risk assessments.

17.
EFSA J ; 17(Suppl 1): e170709, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32626446

RESUMO

This paper argues that value-laden judgements play an important role in regulatory science and risk assessment. These judgements include choices about what topics to study; what questions to ask about those topics; how best to design studies to answer those questions; how to collect, analyse, and interpret data; and how to frame and communicate findings. Rather than defending a 'value-free ideal' for responding to these judgements, the paper calls for a 'value-management ideal' based on three principles: (1) value-laden judgements should be handled as transparently as possible; (2) these judgements should be made in ways that reflect social and ethical priorities; and (3) they should be made in a manner that is informed by engagement among interested and affected parties. Based on these principles, the paper suggests several strategies for moving forward to handle value-laden judgements in regulatory science and risk assessment in a responsible manner. First, decision makers should become more comfortable with scientific disagreement, finding ways to respect different positions on value-laden judgements and formulate policies despite inconclusive evidence. Second, those engaged in regulatory science should explore creative ways to clarify important judgements and communicate how they are being handled. Third, institutional processes for setting standards and guidelines for regulatory science and risk assessment should be scrutinised to ensure that they provide fair opportunities for all interested and affected parties to participate in and inform those processes.

18.
Risk Anal ; 39(3): 571-585, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30176174

RESUMO

Two between-subject experiments explored perceived conflict of interest (COI)-operationalized as perceived procedural unfairness-in a hypothetical public-private research partnership to study the health risks of trans fats. Perceived fairness was measured as subjects' perceptions that health researchers would be willing to listen to a range of voices and minimize bias (i.e., COI) in the context of a research project. Experiment 1 (n = 1,263) randomly assigned research subjects to a partnership that included (1) a combination of an industry partner, a university partner, and a nongovernmental organization (NGO) partner; and (2) one of three processes aimed at mitigating the potential for COI to harm the quality of the research. The procedures included an arm's-length process meant to keep the university-based research team from being influenced by the other partners, an independent advisory board to oversee the project, and a commitment to making all data and analyses openly available. The results suggest that having an industry partner has substantial negative effects on perceived fairness and that the benefit of employing a single COI-mitigation process may be relatively small. Experiment 2 (n = 1,076) assessed a partnership of (1) a university and either an NGO or industry partner and (b) zero, one, two, or three of the three COI-mitigation procedures. Results suggest there is little value in combining COI-mitigation procedures. The study has implications for those who aim to foster confidence in scientific findings for which the underlying research may benefit from industry funding.

19.
N Engl J Med ; 379(11): 1028-1041, 2018 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-30207916

RESUMO

BACKGROUND: Allogeneic hematopoietic stem-cell transplantation is the only curative treatment for patients with myelodysplastic syndrome (MDS). The molecular predictors of disease progression after transplantation are unclear. METHODS: We sequenced bone marrow and skin samples from 90 adults with MDS who underwent allogeneic hematopoietic stem-cell transplantation after a myeloablative or reduced-intensity conditioning regimen. We detected mutations before transplantation using enhanced exome sequencing, and we evaluated mutation clearance by using error-corrected sequencing to genotype mutations in bone marrow samples obtained 30 days after transplantation. In this exploratory study, we evaluated the association of a mutation detected after transplantation with disease progression and survival. RESULTS: Sequencing identified at least one validated somatic mutation before transplantation in 86 of 90 patients (96%); 32 of these patients (37%) had at least one mutation with a maximum variant allele frequency of at least 0.5% (equivalent to 1 heterozygous mutant cell in 100 cells) 30 days after transplantation. Patients with disease progression had mutations with a higher maximum variant allele frequency at 30 days than those who did not (median maximum variant allele frequency, 0.9% vs. 0%; P<0.001). The presence of at least one mutation with a variant allele frequency of at least 0.5% at day 30 was associated with a higher risk of progression (53.1% vs. 13.0%; conditioning regimen-adjusted hazard ratio, 3.86; 95% confidence interval [CI], 1.96 to 7.62; P<0.001) and a lower 1-year rate of progression-free survival than the absence of such a mutation (31.3% vs. 59.3%; conditioning regimen-adjusted hazard ratio for progression or death, 2.22; 95% CI, 1.32 to 3.73; P=0.005). The rate of progression-free survival was lower among patients who had received a reduced-intensity conditioning regimen and had at least one persistent mutation with a variant allele frequency of at least 0.5% at day 30 than among patients with other combinations of conditioning regimen and mutation status (P≤0.001). Multivariate analysis confirmed that patients who had a mutation with a variant allele frequency of at least 0.5% detected at day 30 had a higher risk of progression (hazard ratio, 4.48; 95% CI, 2.21 to 9.08; P<0.001) and a lower 1-year rate of progression-free survival than those who did not (hazard ratio for progression or death, 2.39; 95% CI, 1.40 to 4.09; P=0.002). CONCLUSIONS: The risk of disease progression was higher among patients with MDS in whom persistent disease-associated mutations were detected in the bone marrow 30 days after transplantation than among those in whom these mutations were not detected. (Funded by the Leukemia and Lymphoma Society and others.).


Assuntos
Transplante de Células-Tronco Hematopoéticas , Mutação , Síndromes Mielodisplásicas/genética , Adulto , Exame de Medula Óssea , Análise Mutacional de DNA , Progressão da Doença , Intervalo Livre de Doença , Humanos , Leucemia Mieloide Aguda/genética , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/mortalidade , Síndromes Mielodisplásicas/terapia , Pele/patologia , Análise de Sobrevida , Condicionamento Pré-Transplante , Transplante Homólogo
20.
JCI Insight ; 3(5)2018 03 08.
Artigo em Inglês | MEDLINE | ID: mdl-29515031

RESUMO

Allogeneic hematopoietic cell transplantation (alloHCT) is a potentially curative treatment for myelodysplastic syndromes (MDS), but patients who relapse after transplant have poor outcomes. In order to understand the contribution of tumor clonal evolution to disease progression,we applied exome and error-corrected targeted sequencing coupled with copy number analysis to comprehensively define changes in the clonal architecture of MDS in response to therapy using 51 serially acquired tumor samples from 9 patients who progressed after an alloHCT. We show that small subclones before alloHCT can drive progression after alloHCT. Notably, at least one subclone expanded or emerged at progression in all patients. Newly acquired structural variants (SVs) were present in an emergent/expanding subclone in 8 of 9 patients at progression, implicating the acquisition of SVs as important late subclonal progression events. In addition, pretransplant therapy with azacitidine likely influenced the mutation spectrum and evolution of emergent subclones after alloHCT. Although subclone evolution is common, founding clone mutations are always present at progression and could be detected in the bone marrow as early as 30 and/or 100 days after alloHCT in 6 of 8 (75%) patients, often prior to clinical progression. In conclusion, MDS progression after alloHCT is characterized by subclonal expansion and evolution, which can be influenced by pretransplant therapy.


Assuntos
Evolução Clonal/imunologia , Transplante de Células-Tronco Hematopoéticas , Síndromes Mielodisplásicas/terapia , Recidiva Local de Neoplasia/genética , Adulto , Idoso , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/efeitos adversos , Azacitidina/administração & dosagem , Azacitidina/efeitos adversos , Células da Medula Óssea/efeitos dos fármacos , Células da Medula Óssea/imunologia , Evolução Clonal/efeitos dos fármacos , Células Clonais/efeitos dos fármacos , Células Clonais/imunologia , Análise Mutacional de DNA , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação/efeitos dos fármacos , Agonistas Mieloablativos/administração & dosagem , Agonistas Mieloablativos/efeitos adversos , Síndromes Mielodisplásicas/genética , Síndromes Mielodisplásicas/imunologia , Síndromes Mielodisplásicas/patologia , Recidiva Local de Neoplasia/imunologia , Recidiva Local de Neoplasia/patologia , Condicionamento Pré-Transplante/efeitos adversos , Condicionamento Pré-Transplante/métodos , Transplante Homólogo , Resultado do Tratamento
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