Thesis (M.S.)--Oregon State University, 2008. / Printout. Includes bibliographical references (leaves 89-99). Also available on the World Wide Web.

Submitted by Valquíria Barbieri (kikibarbi@hotmail.com) on 2017-08-30T21:44:32Z No. of bitstreams: 1 DISS_2014_Beluci Bianca Nunes de Siqueira.pdf: 720939 bytes, checksum: f785c41d77a555cc4b6a978ad9366ed8 (MD5) / Approved for entry into archive by Jordan (jordanbiblio@gmail.com) on 2017-09-01T14:03:51Z (GMT) No. of bitstreams: 1 DISS_2014_Beluci Bianca Nunes de Siqueira.pdf: 720939 bytes, checksum: f785c41d77a555cc4b6a978ad9366ed8 (MD5) / Made available in DSpace on 2017-09-01T14:03:51Z (GMT). No. of bitstreams: 1 DISS_2014_Beluci Bianca Nunes de Siqueira.pdf: 720939 bytes, checksum: f785c41d77a555cc4b6a978ad9366ed8 (MD5) Previous issue date: 2014-07-11 / CAPES / Esta pesquisa tem como proposta compreender a experiência de adoecimento de adultos jovens por uma condição crônica: a Leucemia Mielóide Aguda. Ressaltamos nesse estudo a dimensão social, pois essa nova condição é tratada com prognóstico ruim, mutilante, fatal; sendo comparada/associada a desordens físicas, mentais e sociais, além disso, a sociedade deprecia as pessoas adoecidas pelo câncerestigmatizando- as. Trata-se de uma pesquisa qualitativa baseado em pressupostos da fenomenologia de Alfred Schutz. As informações foram obtidas mediante entrevistas semiestruturadas realizada com quatro jovens, na faixa etária de 20 a 28 anos, em fase de manutenção no tratamento em uma unidade de referência oncológica no período de novembro de 2013 até janeiro de 2014, no estado de Mato Groso. Após as entrevistas foi realizada a descrição dos sujeitos entrevistados, e em seguida o agrupamento dos temas principais nas experiências dos adoecidos. Os resultados abrangem: o processo de descoberta do adoecimento por leucemia, em que destacase o diagnóstico realizado com rapidez sendo esse o diferencial entre a vida e a morte; o conceito, sendo a leucemia atribuída a uma doença fatal, contagiosa, silenciosa e invisível; noções causais relacionado a uma doença com causas pluralísticas de acordo com o seu contexto, como hereditariedade, agentes externos e momento marcante negativamente em sua vida; os impactos e as estratégias cotidianas de enfrentamento relatados com maior importância estavam ligados com a aparência corporal, morte vivenciada de amigos e prenúncios da própria morte e o apoio social recebidos tanto pelo apoio informal quanto formal para a realização do tratamento;e as motivações dos sujeitos para as suas ações. A pesquisa demonstrou a complexidade do adoecimento crônico, como o adoecimento marca a vida cotidiana dos sujeitos e como são realizadas as estratégias de enfrentamento na tentativa de integrar a condição crônica ao novo ritmo da vida, resignificando sua experiência com a leucemia. Além disso, possibilita a refletir sobre as práticas de atenção e de gestão oncológica. / This research aims at understanding the experience of illness in young adults with a chronic condition: the Acute Myeloid Leukemia. This study emphasize the social dimension, because this new condition is treated bad, mutilating, fatal prognosis; being compared / associated with physical, mental, and social disorders, moreover, detracts society people with cancer have fallen ill-branding them. This is a qualitative research based on assumptions of phenomenology of Alfred Schutz. Data were obtained through semi-structured interviews conducted with four youths, aged 20-28 years in the maintenance phase of treatment in an oncology referral from November 2013 until January 2014, the state of Mato Groso. After the interviews were performed description of the interviewees, and then grouping the main themes in the experiences of the diseased. The results include: the process of discovery of illness from leukemia, where the highlight is the diagnosis made quickly that being the difference between life and death; the concept, and the leukemia attributed to a fatal, contagious, silent and invisible disease; causal notions related to a disease with pluralistic causes according to its context, such as heredity, external agents and negatively striking moment in your life; impacts and everyday coping strategies reported most importance were linked with body appearance, experienced death of friends and harbingers of death itself and the social support received by both the informal and formal support for the completion of the treatment, and the motivations of the subjects for their actions. Research has demonstrated the complexity of chronic illness, such as illness marks the daily lives of the subjects and how the coping strategies in an attempt to integrate the new chronic condition pace of life are held, redefining his experience with leukemia. Furthermore, it allows to reflect on care practices and oncological management.

Patients with acute promyelocytic leukemia (APL) often present with potentially lifethreatening hemorrhagic diathesis. The underlying pathomechanisms of APLassociated coagulopathy are complex. However, two pathways considered to be APLspecific had been identified: 1) annexin A2 (ANXA2)-associated hyperfibrinolysis and 2) podoplanin (PDPN)-mediated platelet activation and aggregation. In contrast, since disseminated intravascular coagulation (DIC) is far less frequent in patients with non- APL acute myeloid leukemia (AML), the pathophysiology of AML-associated hemorrhagic disorders is not well understood. Furthermore, the potential threat of coagulopathy in non- APL AML patients may be underestimated. Herein, we report a patient with non-APL AML presenting with severe coagulopathy with hyperfibrinolysis. Since his clinical course resembled a prototypical APL-associated hemorrhagic disorder, we hypothesized pathophysiological similarities. Performing multiparametric flow cytometry (MFC) and immunofluorescence imaging (IF) studies, we found the patient’s bone-marrow mononuclear cells (BM-MNC) to express ANXA2 - a biomarker previously thought to be APL-specific. In addition, whole-exome sequencing (WES) on sorted BM-MNC (leukemiaassociated immunophenotype (LAIP)1: ANXAlo, LAIP2: ANXAhi) demonstrated high intratumor heterogeneity. Since ANXA2 regulation is not well understood, further research to determine the coagulopathy-initiating events in AML and APL is indicated. Moreover, ANXA2 and PDPN MFC assessment as a tool to determine the risk of life-threatening DIC in AML and APL patients should be evaluated.

Background: Acute promyelocytic leukemia (APL) is considered a hematologic emergency due to high risk of bleeding and fatal hemorrhages being a major cause of death. Despite lower death rates reported from clinical trials, patient registry data suggest an early death rate of 20%, especially for elderly and frail patients. Therefore, reliable diagnosis is required as treatment with differentiation-inducing agents leads to cure in the majority of patients. However, diagnosis commonly relies on cytomorphology and genetic confirmation of the pathognomonic t(15;17). Yet, the latter is more time consuming and in some regions unavailable. - Methods: In recent years, deep learning (DL) has been evaluated for medical image recognition showing outstanding capabilities in analyzing large amounts of image data and provides reliable classification results. We developed a multi-stage DL platform that automatically reads images of bone marrow smears, accurately segments cells, and subsequently predicts APL using image data only. We retrospectively identified 51 APL patients from previous multicenter trials and compared them to 1048 non-APL acute myeloid leukemia (AML) patients and 236 healthy bone marrow donor samples, respectively. - Results: Our DL platform segments bone marrow cells with a mean average precision and a mean average recall of both 0.97. Further, it achieves high accuracy in detecting APL by distinguishing between APL and non-APL AML as well as APL and healthy donors with an area under the receiver operating characteristic of 0.8575 and 0.9585, respectively, using visual image data only. - Conclusions: Our study underlines not only the feasibility of DL to detect distinct morphologies that accompany a cytogenetic aberration like t(15;17) in APL, but also shows the capability of DL to abstract information from a small medical data set, i. e. 51 APL patients, and infer correct predictions. This demonstrates the suitability of DL to assist in the diagnosis of rare cancer entities. As our DL platform predicts APL from bone marrow smear images alone, this may be used to diagnose APL in regions were molecular or cytogenetic subtyping is not routinely available and raise attention to suspected cases of APL for expert evaluation.