Dissertations / Theses: 'Myeloma patients'

1

Ågren, Brita. "Radiological evaluation of bone marrow transplanted multipel myeloma patients /." Stockholm, 1997. http://diss.kib.ki.se/1997/91-628-2609-3/.

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2

Hansson, Lotta. "Natural and induced idiotype immunity in patients with multiple myeloma /." Stockholm, 2004. http://diss.kib.ki.se/2004/91-7349-820-3/.

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3

Abdalla, Amir Osman. "Immunological and clinical long-term effects of idiotype vaccination in multiple myeloma patients /." Stockholm, 2007. http://diss.kib.ki.se/2007/978-91-7357-114-2/.

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4

Jacobson, Timothy. "A Trans-Dimensional View of Drug Resistance Evolution in Multiple Myeloma Patients." Scholar Commons, 2016. http://scholarcommons.usf.edu/etd/6099.

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Multiple Myeloma (MM) is a treatable, yet incurable, malignancy of bone marrowplasma cells. This cancer affects many patients and many succumb to relapse of tumor burden despite a large number of available chemotherapeutic agents developed for therapy. This is because MM tumors are heterogeneous and receive protection from therapeutic agents by the microenvironment and other mechanisms including homologous MM-MM aggregation. Therefore, therapy failure and frequent patient relapse is due to the evolution of drug resistance, not a lack of available drugs. To analyze and understand this problem, the evolution of drug resistance has been explored and presented herein. We seek to describe the methods through which MM cells become resistant to therapy, and how this resistance evolves throughout a patient’s treatment history. We achieve this in five steps. First we review the patient’s clinical history, including treatments and changes in tumor burden. Second, we trace the evolutionary tree of sub-clones within the tumor burden using standard of care fluorescence in situ hybridization (FISH). Thirdly, immunohistochemistry slides are stained and aligned to quantify the level of environmental protection received by surrounding cells and plasma in the bone marrow microenvironment (coined environment mediated drug resistance score [EMDR]). The fourth analysis type is produced through a novel 384-well plate ex vivo chemosensitivity assay to quantify sensitivity of primary MM cells to chemotherapeutic agents and extrapolate these findings to 90-day clinical response predictions. In addition to direct clinical application in the choice of best treatment, this tool was also used to study changes in sensitivity of patient tumors to other drugs, and it was observed that, upon relapse, in addition to developing resistance to the current line of therapy, tumors become cross-resistant to agents that they were never exposed to. Finally, MM-MM homologous aggregation is quantified to assess the level of drug resistance contributed by clustering of patient tumor cells, which causes upregulation of Bcl-2 expression and other resistance mechanisms1. The findings of such experimentation improve comprehension of the driving factors that contribute to drug resistance evolution on a personalized treatment basis. The aforementioned factors all contribute in varying degrees for unique patient cases, seven of which are presented in depth for this project. In summary: Environmental protection plays a critical initial role in drug resistance, which is followed by increase in tumor genetic heterogeneity as a result of mutations and drug-induced Darwinian selection. Eventually, environment-independent drug resistant subpopulations emerge, allowing the tumor to spread to unexplored areas of the bone marrow while maintaining inherited drug resistant phenotype2. It is our hope that these findings will help in shifting perspective regarding optimal management of MM by finding new therapeutic procedures that address all aspects of drug resistance to minimize chance of relapse and improve quality of life for patients.

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5

Esmaeili, Abbas. "Identifying responders to melphalan and dexamethasone for newly diagnosed multiple myeloma patients." Thesis, Kingston, Ont. : [s.n.], 2008. http://hdl.handle.net/1974/1330.

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6

Gerfen, Ashlee. "Chemomobilization with cyclophosphamide and filgrastim in multiple myeloma patients following lenalidomide treatment." The University of Arizona, 2012. http://hdl.handle.net/10150/623611.

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Class of 2012 Abstract
Specific Aims: Autologous stem cell transplant (ASCT) is the current gold standard following induction therapy to improve survival of multiple myeloma (MM). Lenalidomide (LEN) is used for treatment of MM before ASCT, but exposure may impair autologous peripheral blood stem cell (PBSC) mobilization. Chemomobilization with cyclophosphamide (CTX) has not been evaluated in this setting. CTX + filgrastim was investigated to determine if LEN-associated mobilization impairment can be abrogated. Methods: 36 pts (group A=12 pts who received ≥2 cycles of LEN and group B=24 pts without LEN) were analyzed retrospectively. Baseline characteristics were matched (p>0.05 for all variables). All pts received CTX (median group B, 1.5g/m2; median group A, 3gm/m2(p=0.18)) and filgrastim 10μg/kg/day. Primary outcomes include number of CD34+ cells collected and number of leukapheresis sessions. Secondary outcomes include failure to collect CD34+ cells and total CD34+ cells collected after second leukapheresis. Main Results: Total median number of CD34+ cells collected in group B=9.15x106/kg CD34+ cells and group A=7.43x106/kg CD34+ cells (p=0.159). Median number of apheresis sessions in group B=2 and group A=3 (p=0.42). Two of 12 pts with antecedent LEN usage failed to collect while no patient without previous LEN exposure failed to collect (p=0.105). Total number of CD34+ cells collected after 2 apheresis sessions for group B=8.13x106/kg CD34+ cells and group A=3.34x106/kg CD34+ cells (p=0.06). Conclusions: Chemomobilization with CTX + filgrastim yields robust PBSC collections irrespective of antecedent lenalidomide. There was a trend towards lesser PBSC collection in LEN-treated pts.

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Gerfen, Ashlee, and Myke Green. "Chemomobilization with Cyclophosphamide and Filgrastim in Multiple Myeloma Patients Following Lenalidomide Treatment." The University of Arizona, 2012. http://hdl.handle.net/10150/614472.

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Class of 2012 Abstract
Specific Aims: Autologous stem cell transplant (ASCT) is the current gold standard following induction therapy to improve survival of multiple myeloma (MM). Lenalidomide (LEN) is used for treatment of MM before ASCT, but exposure may impair autologous peripheral blood stem cell (PBSC) mobilization. Chemomobilization with cyclophosphamide (CTX) has not been evaluated in this setting. CTX + filgrastim was investigated to determine if LEN-associated mobilization impairment can be abrogated. Methods: 36 pts (group A=12 pts who received ≥2 cycles of LEN and group B=24 pts without LEN) were analyzed retrospectively. Baseline characteristics were matched (p>0.05 for all variables). All pts received CTX (median group B, 1.5g/m2; median group A, 3gm/m2(p=0.18)) and filgrastim 10µg/kg/day. Primary outcomes include number of CD34+ cells collected and number of leukapheresis sessions. Secondary outcomes include failure to collect CD34+ cells and total CD34+ cells collected after second leukapheresis. Main Results: Total median number of CD34+ cells collected in group B=9.15x106/kg CD34+ cells and group A=7.43x106/kg CD34+ cells (p=0.159). Median number of apheresis sessions in group B=2 and group A=3 (p=0.42). Two of 12 pts with antecedent LEN usage failed to collect while no patient without previous LEN exposure failed to collect (p=0.105). Total number of CD34+ cells collected after 2 apheresis sessions for group B=8.13x106/kg CD34+ cells and group A=3.34x106/kg CD34+ cells (p=0.06). Conclusions: Chemomobilization with CTX + filgrastim yields robust PBSC collections irrespective of antecedent lenalidomide. There was a trend towards lesser PBSC collection in LEN-treated pts.

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8

Raninga, Prahlad Vinodbhai. "Antioxidant Systems, Thioredoxin and DJ-1: Novel Therapeutic Targets in Multiple Myeloma." Thesis, Griffith University, 2017. http://hdl.handle.net/10072/366858.

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Multiple myeloma (MM) is a plasma cell malignancy characterized by an accumulation of malignant clonal plasma cells in the bone marrow (BM). In recent years, many effective anti-MM drugs have been developed including proteasome inhibitors and immunomodulators. Introduction of the proteasome inhibitor bortezomib has improved prognosis and survival in MM patients. However, upon prolonged drug treatment, myeloma cells acquire resistance to the given treatment including bortezomib, resulting in disease relapse. Studies have shown that the BM in myeloma patients is extensively hypoxic (1% O2) compared to the BM in healthy individuals. Hypoxia is a crucial microenvironmental factor that plays an important role in MM disease progression and drug resistance. Due to the development of drug resistance, MM remains an incurable disease with the median survival of only 3 to 5 years. Thus, novel therapeutic strategies are required to kill myeloma cells growing under physiological O2 conditions, including hypoxic microenvironments, and to overcome both acquired and hypoxia-induced drug resistance to improve MM patient survival and prognosis.
Thesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Natural Sciences
Science, Environment, Engineering and Technology
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9

Cho, Yu Kyoung. "Pharmacokinetics and pharmacodynamics of melphalan in multiple myeloma patients to predict clinical adverse outcomes." The Ohio State University, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=osu1468419921.

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10

Jackson, G. H. "Long term bone marrow culture studies of patients with lymphoid malignancies undergoing autologous bone marrow transplantation." Thesis, University of Newcastle Upon Tyne, 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.309068.

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11

Söderlund, Veli. "Combined radiology and cytology in the diagnosis of bone lesions : a study of 494 patients /." Stockholm, 2002. http://diss.kib.ki.se/2002/91-7349-353-8/.

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12

Goodyear, Oliver Charles. "A study of cancer-germline antigen specific T cell responses in patients with multiple myeloma." Thesis, University of Birmingham, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.433641.

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13

Brioli, Annamaria <1982&gt. "The impact of intraclonal heterogeneity on the outcomes of Multiple Myeloma patients treated with new drugs." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2015. http://amsdottorato.unibo.it/6779/.

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Understanding the biology of Multiple Myeloma (MM) is of primary importance in the struggle to achieve a cure for this yet incurable neoplasm. A better knowledge of the mechanism underlying the development of MM can guide us in the development of new treatment strategies. Studies both on solid and haematological tumours have shown that cancer comprises a collection of related but subtly different clones, a feature that has been termed “intra-clonal heterogeneity”. This intra-clonal heterogeneity is likely, from a “Darwinian” natural selection perspective, to be the essential substrate for cancer evolution, disease progression and relapse. In this context the critical mechanism for tumour progression is competition between individual clones (and cancer stem cells) for the same microenvironmental “niche”, combined with the process of adaptation and natural selection. The Darwinian behavioural characteristics of cancer stem cells are applicable to MM. The knowledge that intra-clonal heterogeneity is an important feature of tumours’ biology has changed our way to addressing cancer, now considered as a composite mixture of clones and not as a linear evolving disease. In this variable therapeutic landscape it is important for clinicians and researchers to consider the impact that evolutionary biology and intra-clonal heterogeneity have on the treatment of myeloma and the emergence of treatment resistance. It is clear that if we want to effectively cure myeloma it is of primarily importance to understand disease biology and evolution. Only by doing so will we be able to effectively use all of the new tools we have at our disposal to cure myeloma and to use treatment in the most effective way possible. The aim of the present research project was to investigate at different levels the presence of intra-clonal heterogeneity in MM patients, and to evaluate the impact of treatment on clonal evolution and on patients’ outcomes.

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14

Spary, Lisa Kate. "Rankl expression and chromosome 13 deletions in cell lines from patients with multiple myeloma and osteosarcoma." Thesis, University of the West of England, Bristol, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.444485.

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15

Song, Brian. "Comprehensive Risk Stratification Model for Prognostication and Assisting with Therapeutic Decision-Making for Multiple Myeloma Patients." Thesis, California State University, Long Beach, 2018. http://pqdtopen.proquest.com/#viewpdf?dispub=10839998.

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The goal of the research is to improve current risk stratification models of multiple myeloma by developing a novel statistical decision algorithm. The increase in precision would assist in providing optimal treatments for multiple myeloma cancer patients depending on the risk of progression at the time of diagnosis. If progression of cancer is imminent, then risk-adapted therapy would be a considerable option. Larger amount of data supplied from multiple clinics were gathered to obtain better prognosis. The data are available from the Synapse website under the Multiple Myeloma DREAM Challenge site. Although both genomic variation data and gene expression data were available, the study was done with the latter in conjunction with general patient data. Preliminary research has shown that the microarray data were not standardized among the different clinics, so the study required additional preprocessing before aggregating all data for comprehensive investigation. Accelerated Time Failure model is used to screen insignificant variables for easier processing, reducing 17,308 markers to 4,503. A combination of random forest models and likelihood ratio test is utilized to further reduce potentially significant biomarkers. The remaining biomarkers are used in multiple statistical models to determine the optimal model that best represents the data. The efficacy of the model is checked by using two clinics to train the model to predict the third clinic. The average and standard deviation of the resulting statistics are used to validate the consistency of the model for different clinics. We show that an improvement in current risk stratification models can be obtained.

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16

Redzepovic, Jasmina [Verfasser]. "Meta-analysis in context : Chemotherapy versus chemotherapy combined with bisphosphonate therapy in multiple myeloma patients / Jasmina Redzepovic." Berlin : Freie Universität Berlin, 2009. http://d-nb.info/1023664585/34.

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17

Johansson, Eva. "Central venous access devices in patients with haematological malignancies : care, complications and home treatment /." Stockholm, 2002. http://diss.kib.ki.se/2003/91-7349-414-3/.

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18

Alaterre, Elina. "Identification fine des cellules plasmocytaires normales et tumorales dans la moelle osseuse de patients atteints de myélome multiple en cytométrie en flux." Thesis, Montpellier, 2017. http://www.theses.fr/2017MONTT010.

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Le myélome multiple (MM) est une hémopathie maligne caractérisée par la prolifération d’un clone plasmocytaire tumoral dans la moelle osseuse et d’une accumulation d’une immunoglobuline monoclonale dans le sérum et/ou les urines. La diversité des anomalies cytogénétiques, rendant la maladie plus ou moins agressive, et la variabilité de la réponse au traitement font du MM une maladie hétérogène. Le MM reste incurable dans la majorité des cas avec une médiane de survie de 5 à 7 ans. La rechute après traitement est due à la persistance de cellules tumorales au sein de la moelle osseuse, appelée maladie résiduelle ou en anglais « Minimal Residual Disease » (MRD). La cytométrie en flux multiparamétrique (CFM) est une technique sensible, simple et rapide qui permet d’identifier et de caractériser des cellules d’intérêt dans un échantillon biologique. C’est dans le but de simplifier le suivi de la MRD du MM que nous avons développé une solution complète basée sur la CFM. Cette solution comprend (i) la conception d’un panel à 5 couleurs, composés des anticorps (Ac) anti-CD38, anti-kappa et anti-lambda pour identifier les plasmocytes totaux et de deux pools d’Ac couplés au même fluorochrome (anti-CD19/anti-CD27, pool négatif et anti-CD56/anti-CD117/anti-CD200, pool positif) pour détecter les plasmocytes tumoraux ; (ii) le développement d’un préparateur afin d’automatiser l’ensemble des étapes de préparation de l’échantillon ; et (iii) l’automatisation de l’analyse des résultats de CFM grâce à un logiciel que nous avons créé. Cette solution simple et entièrement automatisée permet d’augmenter la reproductibilité et la productivité, de diminuer le coût du test, sans altérer la sensibilité ou la spécificité. En parallèle de ces travaux, nous avons construit un score de risque simple basé sur l’expression de gènes codant pour des protéines de surface (CD24, CD27, CD36 et CD302) permettant de prédire la survie des patients atteints de MM au diagnostic ainsi qu’à la rechute
Multiple myeloma (MM) is a hematological malignancy characterized by clonal plasma cell proliferation in bone marrow and abnormal monoclonal immunoglobulin accumulation in the serum and/or urine. The heterogeneity of the disease is partly due to the cytogenetic abnormalities diversity making the disease more or less aggressive. MM is incurable in the majority of cases with a median survival between 5 and 7 years. The persistence of abnormal plasma cells in bone marrow after treatment is called minimal residual disease (MRD) and leads to the patient relapse. Multiparametric flow cytometry (MFC) is a sensitive, simple and fast technique to identify and characterize cells of interest in biological samples. In order to simplify MRD follow-up we have developed a complete solution based on MFC. This solution includes (i) the 5-color panel design, composed of anti-CD38, anti-kappa and anti-lambda antibodies (Ab) to identify total plasma cell population and two pools of Ab paired to the same fluorophore (anti-CD19/anti-CD27, negative pool and anti-CD56/anti-CD117/anti-CD200, positive pool) to detect abnormal plasma cells; (ii) the development of a device used to automatically prepare biological samples before MFC; and (iii) the analysis automation of MFC results using a homemade software. This fully automated solution increases reproducibility and productivity, decreases processing and analyzing time as well as test cost, without affecting sensibility and specificity. In parallel, we have built a simple risk score based on gene expression encoding surface proteins (CD24, CD27, CD36 and CD302) providing MM patient outcome at diagnostic and MRD follow-up

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Manchulenko, Cynthia. "Frequency of peripheral neuropathy and injection site reactions in patients with multiple myeloma receiving subcutaneous versus intravenous bortezomib." Thesis, University of British Columbia, 2015. http://hdl.handle.net/2429/52695.

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Multiple myeloma is an incurable hematological malignancy with patients living on average 3 to 6 years after diagnosis. Bortezomib is widely used to treat multiple myeloma. Peripheral neuropathy has been a major side effect associated with bortezomib treatment, and occurs in 47% to 64% of patients. Therefore, strategies to minimize this dose limiting toxicity have been studied and protocols have been revised accordingly. Bortezomib administered subcutaneously instead of intravenously is one strategy that has shown to decrease the incidence of peripheral neuropathy, is well-tolerated and equally as efficacious as bortezomib administered intravenously. Injection site reactions have been reported as mild. Furthermore, as far as the author is aware there is currently no published literature discussing the safety and tolerability of the back of the arm as an injection site for bortezomib. This was a retrospective, chart review of 53 subjects with multiple myeloma, conducted in two large academic medical centres in British Columbia. Incidence of peripheral neuropathy was collected and compared between those who had received bortezomib via intravenous and subcutaneous routes. Incidence of injection site reactions related to subcutaneous administration of bortezomib were also collected, and a comparison was done between the sites of injection (back of the arm, abdomen and thigh). Overall, peripheral neuropathy rates in this study were 28% (n=15/53). There was no statistically significant difference between frequencies of peripheral neuropathy for patients who received bortezomib via intravenous or subcutaneous routes (p = .490). There were a total of 861 injections, with 294 injections to the back of the arm, 487 injections to the abdomen, 130 injections to an unknown site and only one injection in the thigh. Of the 861 injections, there were eight (2%) Grade 1 injection reactions in the abdomen, and one Grade 3 injection reaction, in the thigh. None were reported in the back of the arm. In conclusion, a prospective study with a larger sample size is needed to examine if subcutaneously injected bortezomib results in less peripheral neuropathy than intravenously injected bortezomib. Furthermore, subcutaneously injected bortezomib is safe and well tolerated when injected in the back of the arm.
Applied Science, Faculty of
Nursing, School of
Graduate

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20

Kiaii, Shahryar. "T cells in patients with B-cell chronic lymphocytic leukemia (B-CLL) and multiple myeloma (MM) : an immunological study /." Stockholm : Karolinska institutet, 2007. http://diss.kib.ki.se/2007/978-91-7357-050-3/.

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21

Zammit, Carmen. "The art of healing : A journey through cancer : Implications for art therapy." Thesis, Edith Cowan University, Research Online, Perth, Western Australia, 1999. https://ro.ecu.edu.au/theses/1224.

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This thesis is designed to investigate how art assisted in the healing process of a person suffering from a life threatening illness. The research method used is a clinical case study. This study is a form of evaluative research, a systematic data-based inquiry concerning the participant's engagement with art in her healing process, a process which unfolds as being both life affirming and spiritually enriching. This case study takes a qualitative approach, with its emphasis on the participant's own account of her behaviour. The participant is a fifty-three year old woman, a psychiatrist and psychotherapist, who was diagnosed with multiple myeloma seven years ago. Multiple myeloma is cancer of the bone marrow and blood, a medically incurable form of cancer (Mayo Clinic, 1996; Macpherson, 1995). The principles of Holistic Medicine and Arts Medicine provide the theoretical framework. Data was accumulated from multiple sources: in-depth, open-ended interviews; direct observation; video-tapes; audio-tapes; written documentation and artwork. Art therapy literature reveals a scarcity of formal evaluative research in the area of how art assists people in their healing of a life-threatening illness (Malchiodi, 1993a, l993b). This research project follows the tradition of existing studies and formally documents one person's journey. The aim is to assist in efforts to develop art interventions that will promote healing for people suffering from serious illnesses, and in many cases, those facing imminent death.

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22

Dunnett, Susan. "The transformed consumer : collective practices and identity work in an emotional community." Thesis, University of Stirling, 2009. http://hdl.handle.net/1893/2289.

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This interpretive consumer research study interrogates the idea that people turn to consumption as a means of self-determination. Proceeding from the understanding that the consumer enacts the development of their identity within the marketplace, it takes as its subject those in transition. Its context is a support group community of people brought together by an illness - multiple myeloma. Here, through a phenomenological approach designed to explore the lived experience of illness, the thesis discovers community to be the enabling context for the consumer’s negotiation of both selfhood and the market. Conclusions are drawn about the incremental, complex nature of identity work, and the collective practices that empower it. It is found that the marketplace requires significant mediation, but that the social resources of the community can equip the consumer to navigate its challenges. This transformation is manifested in the newly-diagnosed patient’s journey from dislocation and passivity to the empowered status of ‘skilled consumer’. The importance of the often-overlooked emotional texture of exchange within consumption communities is highlighted. In conclusion, it is offered that this study extends the concept of communities of practice into the field of consumption.

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Akhtar, Shabana. "Molecular mechanisms of myricetin bulk and nano forms mediating genoprotective and genotoxic effects in lymphocytes from pre-cancerous and myeloma patients." Thesis, University of Bradford, 2018. http://hdl.handle.net/10454/17367.

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Cancer is one of the leading causes of death across the globe which needs appropriate and cost-effective treatment. Several recent studies have suggested that dietary intake of various flavonoids such as myricetin have a protective effect against different types of cancers and cardiovascular diseases. The present study was conducted to investigate the genoprotective and genotoxic effects of myricetin nano and bulk forms on the lymphocytes from pre-cancerous and multiple myeloma cancer patients compared to those from healthy individuals. Also, to investigate the protective potential of myricetin bulk and nano against the oxidative stress produced in vitro by 2- amino-1-methyl-6 phenylimidazo [4, 5-b] pyridine and reactive oxygen species- induced DNA damage using the Comet assay, micronucleus assay, cellular reactive oxygen species and glutathione detection assay, Western blotting, real-time polymerase chain reaction and immunofluorescence. Lymphocytes from the patient groups showed significantly higher levels of basal DNA damage compared to the lymphocytes from healthy individuals which was observed throughout the in vitro treatment. Myricetin in both forms has not induced any significant DNA damage in all of the investigative groups at selective lower concentrations; in fact, the results demonstrate a reduction in DNA damage upon treating with myricetin nano in lymphocytes from pre-cancerous patients demonstrated by significant reduction in micronuclei formation in mononucleated cells. DNA repair capacity of myricetin bulk and nano was determined by co-treating the drugs with hydrogen peroxide. Myricetin significantly reduced the oxidative stress related damage caused by hydrogen peroxide, where myricetin nano seemed to be more effective employing the Comet assay. In the presence of myricetin bulk and nano, the damaging effects of 2- amino-1-methyl-6 phenylimidazo [4,5-b] pyridine were considerably decreased, where myricetin nano was more effective. This could be because nanoparticles have a larger surface area which could improve their reactivity and also the reduction in size of the particles could improve the anti-cancer properties of this compound. Myricetin has shown genoprotective and anti-oxidant effects by demonstrating the potential to reduce DNA damage caused by over-production of reactive oxygen species and oxidative stress. It has also shown anti-cancer potential in the lymphocytes from multiple myeloma patients by regulating the apoptosis related proteins, dependent on oxidative stress. Therefore, this study suggests that myricetin supplementation in our regular diet with enhanced bioavailability could have potential health beneficial effects and possibly protect against various diseases including cancer.

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Puyade, Mathieu. "Parcours de soins des patients atteints d'hémopathies malignes en Poitou-Charentes." Thesis, Poitiers, 2017. http://www.theses.fr/2017POIT1407/document.

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La réduction des inégalités d'accès aux soins a toujours été un axe majeur des politiques de lutte contre le cancer. Alors qu'il existe de nombreuses études en cancérologie solide, peu d'études avec une méthodologie correcte existent en onco-hématologie, notamment chez les patients atteints de Myélome Multiple (MM). Cette maladie a vu son pronostic transformé par l'arrivée de nouvelles thérapeutiques dont l'usage a été rapidement intégré dans les recommandations de la Société Française d'Hématologie. L'objectif de travail intitulé Parcours de Soins des patients atteints d'hémopathie maligne en Poitou Charentes était donc de décrire et d'analyser les écarts aux recommandations, en prenant le MM comme premier exemple. Grâce au registre des Cancers Poitou-Charentes et à l'exhaustivité des cas qu'il assure, notre travail a permis de déterminer des variables associées à une inégalité d'accès aux soins. Ces variables sont démographiques (âge, distance entre le domicile et l'hôpital), liées à la tumeur (maladie symptomatique ou non), mais aussi organisationnelles (niveau de l'hôpital, passage en réunion de concertation pluridisciplinaire). De plus nous avons pu montrer que ces inégalités avaient un impact sur la survie globale des patients, notamment chez les plus âgés. Notre travail se poursuit par une analyse plus fine de la survie globale et l'étude des longs survivants du Myélome Multiple. A plus long terme, nous souhaitons appliquer cette approche à d'autres hémopathies
French national Cancer plans aimed to reduce health care inequalities. These inequalities are well known in solid cancers but few data with correct methodology exist in Hematology, especially in Multiple Myeloma (MM). The new treatments in this disease have dramatically improved Overall Survival. So guidelines of the Société Française d'Hématologie have quickly recommended the use of these new drugs. The aim of our work: Care Pathway of patients with hematological malignancies in Poitou Charentes area was to describe and analyze non compliance to guidelines. Based on the exhaustivity of the Poitou Charentes Cancer Registry, our work revealed variables associated with healthcare inequalities. They were demographical (age, distance between home and hospital), tumor-related (symptomatic MM or not) but also organizational (level of the hospital, multidisciplinary meeting). Moreover we showed that those inequalities had a negative impact on overall survival, especially in elderly people. Our work continues with more accurate analysis of overall survival and a study on MM long survivors. Longer-term studies would be to transfer this approach to other hemopathies

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Cachia, Elaine. "The involvement of the central nervous system in chemotherapy-induced peripheral neuropathy, and the symptom burden and health-related quality of life in patients with multiple myeloma." Thesis, University of Sheffield, 2013. http://etheses.whiterose.ac.uk/3885/.

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Background: Modern treatments extend life expectancy in patients with multiple myeloma (MM) and a high incidence of chemotherapy-induced peripheral neuropathy (CIPN) has evolved. The impact of disease and treatment on health-related quality of life (HRQoL) in MM is poorly characterised. This work aimed to investigate (i) the neuroanatomical functional correlates of pain processing in CIPN and (ii) HRQoL and symptom burden in advanced, intensively-treated myeloma. Methods: First study: twelve neurophysiologically assessed patients with CIPN and 12 healthy volunteers underwent fMRI to determine the brain's haemodynamic response to noxious heat stimuli applied to the extremities. Second study: detailed HRQoL and neuropathy assessments, serum IL-6 and TNF-α levels were measured in 32 patients with MM (median age = 61 yrs, duration of disease = 5.5 yrs) who had previously undergone 3 lines of treatment. Results: First study: Neurophysiological testing in MM patients confirmed peripheral neuropathy in the feet. Significant hypo-activation of the right superior frontal gyrus and hyper-activation in the precuneus were present in response to foot stimulation in the CIPN-myeloma compared to healthy control groups. Significant positive correlation existed between neuropathy score and frontal opercula activation, during foot stimulation in CIPN-myeloma patients. Second study: Thirty-two MM patients (duration of disease = 5.5 yrs) were recruited. Physical functioning was significantly compromised (p < 0.001) and associated with progressive work disability and concerns regarding loss of independence. Fatigue and pain were the predominant symptoms, impacting negatively on physical functioning (p < 0.001). Half of the patients reported neuropathic pain. This sub-group scored lower measures of physical, role and social functioning on EORTC QLQ-C30 and future perspectives from the EORTC MY20 assessments compared to patients without neuropathy. Average pain and pain interference from the BPI-SF were positively correlated (p < 0.05 and p < 0.005, respectively) with serum IL-6 levels. Conclusion: Patients with MM suffer from a high peripheral neuropathy symptomatology burden, leading to a worsening functioning and increased pain. FMRI data indicates that heat-pain stimuli evoke differential activation of distinct cortical regions, suggesting different central pain processing mechanisms in CIPN-myeloma patients. Despite disease control and supportive care, intensively-treated myeloma survivors have significantly compromised HRQoL related to symptom burden.

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Fonte, Valéria Hartt Pereira e. Lopes da. "Sociedade e conhecimento leigo: o desafio da equidade em saúde na experiência da International Myeloma Foundation no Brasil." Instituto de Comunicação e Informação Científica e Tecnológica em Saúde, 2013. https://www.arca.fiocruz.br/handle/icict/7096.

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Submitted by Gentil Jeorgina (jeorgina@icict.fiocruz.br) on 2013-10-09T16:15:12Z No. of bitstreams: 1 Valéria Hartt.pdf: 1919843 bytes, checksum: 68a6cd38069d53b02f4eb969f570af19 (MD5)
Made available in DSpace on 2013-10-09T16:15:12Z (GMT). No. of bitstreams: 1 Valéria Hartt.pdf: 1919843 bytes, checksum: 68a6cd38069d53b02f4eb969f570af19 (MD5) Previous issue date: 2013
Fundação Oswaldo Cruz. Instituto de Comunicação e Informação Científica e Tecnológica em Saúde. Rio de Janeiro, RJ, Brasil
Nesse recorte de pesquisa, o conceito de conhecimento leigo é ponto de partida e fio condutor para compreender as práticas de participação e ativismo de uma organização de pacientes de câncer, aqui na experiência da International Myeloma Foundation no Brasil (IMF). É a perspectiva informacional que ancora a meta de identificar os contornos do conhecimento leigo da representação brasileira da IMF para dar relevo aos sentidos de equidade em saúde na atenção oncológica. Os resultados apontam para uma forma de mobilização cidadã capaz de abrigar a produção social do conhecimento científico, mas mostram que a prática de advocacia em saúde ainda precisa avançar no Brasil como reflexo dessa nova forma de construção do conhecimento.
In this research outline, the concept of lay knowledge is a starting point and guideline for understanding the practices of participation and activism of a cancer patients organization, here through the experience of the International Myeloma Foundation (IMF) in Brazil. It is the informational perspective that anchors the goal of identifying the contours of lay knowledge of Brazilian representation of the IMF to emphasize the senses of equity in health in cancer care. The results point to a form of citizen mobilization able to shelter the social production of scientific knowledge, but show that the practice of health advocacy still needs to advance in Brazil as a result of this new form of knowledge construction.

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Lyzbicki, Barnaba <1983&gt. "The impact of polymorphisms in P-gp, DNA repair and folic acid metabolism genes in newly diagnosed multiple myeloma patients treated with thalidomide plus dexamethasone, with or without bortezomib." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2012. http://amsdottorato.unibo.it/4802/.

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The principle aim of this study was to investigate biological predictors of response and resistance to multiple myeloma treatment. Two hypothesis had been proposed as responsible of responsiveness: SNPs in DNA repair and Folate pathway, and P-gp dependent efflux. As a first objective, panel of SNPs in DNA repair and Folate pathway genes, were analyzed. It was a retrospective study in a group of 454, previously untreated, MM patients enrolled in a randomized phase III open-label study. Results show that some SNPs in Folate pathway are correlated with response to MM treatment. MTR genotype was associated with favorable response in the overall population of MM patients. However, this relation, disappear after adjustment for treatment response. When poor responder includes very good partial response, partial response and stable/progressive disease MTFHR rs1801131 genotype was associated with poor response to therapy. This relation - unlike in MTR – was still significant after adjustment for treatment response. Identification of this genetic variant in MM patients could be used as an independent prognostic factor for therapeutic outcome in the clinical practice. In the second objective, basic disposition characteristics of bortezomib was investigated. We demonstrated that bortezomib is a P-gp substrate in a bi-directional transport study. We obtain apparent permeability rate values that together with solubility values can have a crucial implication in better understanding of bortezomib pharmacokinetics with respect to the importance of membrane transporters. Subsequently, in view of the importance of P-gp for bortezomib responsiveness a panel of SNPs in ABCB1 gene - coding for P-gp - were analyzed. In particular we analyzed five SNPs, none of them however correlated with treatment responsiveness. However, we found a significant association between ABCB1 variants and cytogenetic abnormalities. In particular, deletion of chromosome 17 and t(4;14) translocation were present in patients harboring rs60023214 and rs2038502 variants respectively.

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Woerner, Sandra Maria [Verfasser], Monika [Akademischer Betreuer] Engelhardt, and Robert [Akademischer Betreuer] Zeiser. "Establishment of a 6-, 8- and 10-color multiparameter flow cytometry assay for the detection of minimal residual disease in multiple myeloma patients: challenging diversity in a straightforward approach." Freiburg : Universität, 2019. http://d-nb.info/1233196715/34.

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Andre, Thibaud. "Caractérisation des cellules stromales mésenchymateuses médullaires chez les sujets normaux et les patients atteints de myélome multiple: lien avec les lésions ostéolytiques et les réponses au traitement." Doctoral thesis, Universite Libre de Bruxelles, 2014. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/209313.

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Le myélome multiple (MM) est une hémopathie maligne de la lignée B qui se manifeste par

une accumulation de plasmocytes monoclonaux dans la moelle osseuse. Le MM se caractérise par

la nature inéluctable de ses rechutes de plus en plus réfractaires au traitement. Au sein de la moelle

osseuse, les cellules malignes interagissent avec leur microenvironnement notamment composé de

cellules stromales mésenchymateuses (CSM). Les CSM apportent un soutien aux cellules

plasmocytaires (PC) malignes via des interactions cellulaires directes (VLA-4, VCAM-1, CD44,…)

ou par la production de cytokines (IL-6, SDF1, VEGF,…). De ces interactions résulte l’apparition

d’altérations constitutives au sein des MM-CSM telles qu’une production réduite de dépôts de

calcium et une augmentation de la sécrétion de nombreux facteurs (IL-6, GDF-15, etc.).

L’objectif de ce travail est de mieux caractériser les anomalies constitutives (génomiques,

prolifératives, immunomodulatrices, etc.) des MM-CSM et d'évaluer l’impact des traitements reçus

par les patients sur ces anomalies. Ces analyses permettront de mieux définir le rôle des CSM dans

la physiopathologie et la progression de la maladie afin de mettre en évidence d’éventuelles cibles

thérapeutiques.

Compte tenu de l’altération de nombreux acteurs du cycle cellulaire mise en évidence par

notre analyse du profil d’expression génique des MM-CSM après comparaison avec celui des CSM

de donneurs sains (DS-CSM), nous avons décidé d’étudier leurs capacités prolifératives. Nos

observations démontrent que a) les MM-CSM sont caractérisées par une réduction de leur

clonogénicité et par un temps de doublement plus important par rapport aux DS-CSM b) l’entrée

précoce des MM-CSM en sénescence est confirmée par l'augmentation drastique du nombre de

cellules exprimant la « senescence-associated β-galactosidase », par l’augmentation de la taille

cellulaire, par l’expression spécifique de membres du « senescence-associated secretory profile »

(SASP) et par la surexpression de TP53 et TP21, deux facteurs importants du cycle cellulaire et de

la sénescence c) l’ostéoblastogenèse des MM-CSM est altérée en raison de ce processus de

sénescence, à savoir, une réduction de la production de calcium et une hausse précoce de l’activité

de la phosphatase alcaline des MM-CSM par rapport aux DS-CSM d) l’activité de support à

l’hématopoïèse des MM-CSM est augmentée (« increased Blast-Colony Forming Cells and LongTerm Culture Initiating Cells »).

Dans la seconde partie de ce travail, on s’est intéressée plus particulièrement aux capacités

immunomodulatrices des MM-CSM. Nous avons observé, par réaction mixte lymphocytaire et

stimulation mitogénique (PHA/IL-2), a) une réduction de l’inhibition de la prolifération des

lymphocytes T activés en présence de MM-CSM par rapport aux DS-CSM b) une inversion du ratio

Th17/Treg lorsque des lymphocytes T activés sont cultivés en présence de MM-CSM par rapport

aux DS-CSM ;les mécanismes potentiellement impliqués dans ces altérations ont été investigués c)

les MM-CSM présentaient une expression anormale du CD40/40L, VCAM1, ICAM-1, LFA-3

HLA-DR et HLA-ABC et des taux d’IL-6 et d’IL-10 altérés ont été mesuré dans le milieu de

culture lorsque les lymphocytes T activés étaient cultivés en présence de MM-CSM par rapport aux

DS-CSM.

Nos résultats suggèrent que les MM-CSM entrent précocement en sénescence avec de

profondes altérations de leurs propriétés biologiques et notamment leur capacités

d'immunomodulation et de différenciation ostéogénique. Nous concluons que l’entrée en

sénescence des MM-CSM pourrait être à l’origine d’une altération du microenvironnement tumoral

qui favoriserait rechutes et résistances aux traitements.
Doctorat en Sciences biomédicales et pharmaceutiques
info:eu-repo/semantics/nonPublished

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Rozanski, Marta. "Bendamustin in Kombination mit Thalidomid und Prednisolon (BPT) bei Patienten mit rezidiviertem oder refraktärem Multiplem Myelom: Ergebnisse einer Phase-I-Studie." Doctoral thesis, Universitätsbibliothek Leipzig, 2012. http://nbn-resolving.de/urn:nbn:de:bsz:15-qucosa-97058.

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Thalidomid ist eine in der Therapie des fortgeschrittenen refraktären oder rezidivierten multiplen Myeloms (MM) wirksame Substanz, obwohl dosislimitierende Toxizitäten (DLT) ihren Einsatz beschränken können. In der vorliegenden Phase-I-Studie mit 28 Patienten mit rezidiviertem oder refraktärem MM nach konventioneller Chemotherapie oder Hochdosis (HD)-Chemotherapie mit Stammzelltransplantation (SCT) konnte gezeigt werden, dass eine Kombination von niedrig dosiertem Thalidomid mit Bendamustin und Prednisolon (BPT) die Wirksamkeit beibehält oder erhöht und gleichzeitig keine DLT auftritt. Die BPT-Therapie umfasste eine Dosis von Bendamustin (60mg/m2) Tag 1, 8 und 15 und Prednisolon (100mg) Tag 1, 8, 15 und 22, und eine eskalierende tägliche Dosis Thalidomid (50, 100, 200mg). Die Behandlungszyklen wurden alle 28 Tage bis zum Auftreten des maximalen Ansprechens, DLT oder Fortschreiten der Erkrankung wiederholt. 24 Patienten sprachen nach mindestens zwei Zyklen auf die Therapie an (vier komplette, sechs sehr gute partielle und 14 partielle Remissionen). Das mediane progressionsfreie Überleben und Gesamtüberleben für alle Patienten betrug 11 und 19 Monate. Nur leichte oder mittelschwere nicht-hämatologische Nebenwirkungen wurden beobachtet und kein Patient entwickelte dosislimitierende Hämatotoxizitäten. Die BPT-Therapie weist bei Patienten mit rezidiviertem oder refraktärem MM eine gute Verträglichkeit mit einem Ansprechen von über 80% auf. Die maximal tolerierte Dosis von Thalidomid wurde in dieser Studie nicht erreicht.

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Jysky, Camilla. "Poliklinisering och dess samband med cytostatikarelaterat fördröjt illamående och kräkningar hos patienter som genomgått autolog stamcellstransplantation." Thesis, Uppsala universitet, Institutionen för folkhälso- och vårdvetenskap, 2013. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-218159.

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Introduktion Autolog stamcellstransplantation är idag en vanlig behandling vid myelom och högmaligna lymfom hos patienter <65 år utan omfattande komorbiditet. Behandlingen delas upp i fem faser: induktionsbehandling, stamcellsmobilisering, stamcellsskörd, konditionering med högdoscytostatika och stamcellsåtergivning/transplantation. Initialt behandlades alla patienter som genomgick autolog stamcellstransplantation inom slutenvården under den sista behandlingsfasen, det vill säga i samband med konditionering och stamcellsåtergivning. Sedan 1990-talet har man dock på många håll i världen övergått till poliklinisk vårdform för denna patientgrupp. Detta innebär att patienten genomgår stamcellstransplantationen inom slutenvården men efter detta behandlas som öppenvårdspatient med fasta återbesök på sin hemklinik under posttransplantfasen. Poliklinisk vårdform har visat sig vara en säker, uppskattad och kostnadseffektiv vårdform som inte medför större risker för patienten och som inte ökar mortalitet och/eller morbiditet i samband autolog stamcellstransplantation. Syfte Syftet med denna studie är att undersöka om det föreligger skillnad i grad av cytostatikarelaterat fördröjt illamående och kräkningar mellan patienter som vårdats polikliniskt jämfört med patienter som vårdats inneliggande på vårdavdelning efter autolog stamcellstransplantation. Metod Studiepopulationen utgörs av 91 patienter varav 33 vårdades polikliniskt och 58 vårdades inom slutenvården efter autolog stamcellstransplantation. Patienterna fyllde i en illamåendedagbok i samband med behandlingen varpå dessa analyserades utifrån variabler gällande cytostatikarelaterat fördröjt illamående och kräkningar. Resultat Resultatet visar att de polikliniserade patienterna mår generellt bättre än de icke- polikliniserade patienterna vad gäller cytostatikarelaterat fördröjt illamående och kräkningar. Sammanfattning Föreliggande studie indikerar ett positivt samband mellan poliklinisk vårdform och lägre incidens av cytostatikarelaterat fördröjt illamående och kräkningar hos patienter som genomgår autolog stamcellstransplantation.
Introduction Treatment for myeloma and lymphoma today typically involves autologous stem cell transplantation for patients <65 years without coexisting comorbidity. The treatment consists of five stages: induction treatment, stem cell mobilisation, stem cell harvest, conditioning with high dose chemotherapy and stem cell rescue (transplantation). Historically all patients treated with autologous stem cell transplantation received treatment as inpatients but this practice has since the 1990ies, due to for instance financial reasons, gradually shifted into an outpatient approach to this line of care. Thus, for the patient the outpatient approach entails myeloablative conditioning and stem cell transplantation as inpatient followed by post transplant care as outpatient part of the home clinic’s outpatient program. Outpatient care following autologous stem cell transplantation has proven to be a safe, highly appreciated and cost effective method of care without any adverse effects on behalf of the patients with regards to clinical outcome, mortality and/or comorbidity. Objectives The aim of this study is to ascertain whether or not there is a difference in degree of chemotherapy-induced delayed nausea and vomiting between an outpatient population and an inpatient population following autologous stem cell transplantation. Methods A total of 91 patients, 33 of whom were included in an outpatient program while remaining 58 were treated as regular inpatients, participated in the study. Patients each day filled out a diary with regards to nausea and emesis during the entire treatment phase. Submitted data was then analysed concerning parameters related to chemotherapy-induced delayed nausea and vomiting. Results The result shows that the outpatient population suffers less in general than the inpatient population in terms of chemotherapy-induced delayed nausea and vomiting. Conclusion To conclude, this study suggests a positive correlation between outpatient care following autologous stem cell transplantation and a lower incidence of chemotherapy-induced delayed nausea and vomiting.

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Gengenbach, Laura Sophie [Verfasser], and Monika [Akademischer Betreuer] Engelhardt. "Navigation in der sich wandelnden Behandlungslandschaft des Multiplen Myeloms: Dezidierte Analyse der applizierten Chemotherapien von 287 am Universitätsklinikum Freiburg behandelten Multiplen Myelom Patienten." Freiburg : Universität, 2019. http://d-nb.info/1200352696/34.

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Bahuaud, Mathilde. "Vaccination anti-pneumococcique chez les sujets à risque d'infections invasives à pneumocoques et prévention de l'hyporéponse Immunogenicity and persistence of the 13-valent pneumococcal conjugate vaccine (PCV13) in patients with untreated smoldering multiple myeloma (SMM): a pilot study Immunogenicity and persistence of a prime-boost re-vaccination strategy for pneumococcal vaccines in patients with rheumatoid arthritis Pneumococcal vaccination in patients with systemic lupus erythematosus: a multicenter placebo-controlled randomized double-blind study Prevention of hyporesponsiveness by modulation of schedule and doses of pneumococcal vaccine immunization." Thesis, Sorbonne Paris Cité, 2018. http://www.theses.fr/2018USPCB067.

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Deux vaccins sont actuellement disponibles pour la prévention des infections invasives à pneumocoques (IIP) : un vaccin polysaccharidique Pneumovax® (PPV23) et un vaccin conjugué Prevenar13® (PCV13), induisant respectivement une protection contre 23 et 13 sérotypes. Le PPV23 est considéré comme faiblement immunogène, en particulier chez les personnes âgées et les patients immunodéprimés. Le PCV13, en revanche, en raison de la conjugaison à une protéine porteuse, présente l'avantage d'induire une réponse immunitaire T-dépendante, non observée avec le vaccin PPV23. Dans notre travail nous avons donc évalué l'impact des stratégies vaccinales utilisant le PCV13 et le PPV23 sur différentes populations de patients à risque. Dans une première étude, nos résultats sur la vaccination anti-pneumococcique chez des patients atteints de myélome indolent (SMM) ont montré qu'une dose de PCV13 seul, induisait une réponse immune transitoire et de faible persistance. Ces résultats suggéraient l'utilisation d'un schéma vaccinal incluant plusieurs doses de PCV13 ou une association avec le PPV23. Depuis 2013, ce schéma combiné du PCV13 et du PPV23 est le schéma recommandé par la Haute Autorité de Santé en France chez les patients à risque, avec les délais suivants : une dose de PCV13 suivie d'une dose de PPV23, 8 semaines après. Nous avons par la suite étudié cette stratégie vaccinale combinée chez des patients à risque d'IIP : patients atteints de lupus érythémateux systémique (SLE) et patients atteints de polyarthrite rhumatoïde (PR). Nos résultats montrent une immunogénicité à court terme de la stratégie combinée, mais une protection qui ne persiste pas au-delà de deux ans. De façon surprenante, les taux d'anticorps 2 ans après la vaccination, sont inférieurs aux taux pré-vaccinaux pour les patients PR. Cet effet délétère du PPV23 sur la réponse vaccinale induite par le PCV13 est appelé hyporéponse. Ce phénomène, observé chez les patients PR, ne se retrouve pas chez les patients SLE dont la vaccination PPV23 a été effectuée plus à distance du PCV13. Ces résultats suggèrent que le schéma vaccinal plus tardif (c'est-à-dire une vaccination par le PPV23 six mois après le PCV13 au lieu de deux mois) inhiberait le phénomène d'hyporéponse. Dans une troisième partie, nous avons comparé différents schéma vaccinaux modulant les doses des vaccins et les délais d'injection chez des volontaires sains mais également dans un modèle murin d'hyporéponse développé au sein du laboratoire. Notre hypothèse était que la modulation du schéma vaccinal utilisant les 2 vaccins pouvait à la fois induire une protection à long terme et prévenir l'hyporéponse. Nos résultats ont montré que l'utilisation d'une dose diminuée de PPV23 ou l'injection concomitante des deux vaccins n'empêchaient pas l'hyporéponse. En revanche, en allongeant le délai entre le PCV13 et le PPV23, le phénomène d'hyporéponse est limité. Des études cliniques chez les patients à risque d'IIP sont nécessaires afin d'évaluer une stratégie combinée tardive, où le PPV23 serait reçu au moins 6 à 12 mois après le PCV13
Two vaccines are currently available for the prevention of invasive pneumococcal diseases (IPD): a polysaccharide vaccine, Pneumovax® (PPV23) and a conjugate vaccine, Prevenar13® (PCV13), inducing protection against 23 and 13 serotypes, respectively. PPV23 is considered to be weakly immunogenic, particularly in the elderly and immunocompromised patients. PCV13, however, due to the conjugation to a carrier protein, has the advantage of inducing a T-dependent immune response, not observed with PPV23 vaccine. In our work, we therefore evaluated the impact of vaccine strategies using PCV13 and PPV23 on different populations of patients at risk of IPD. In a first study, our results on anti-pneumococcal vaccination in patients with smoldering myeloma (SMM) showed that a single dose of PCV13 induces a transient immune response and long term persistence. These results suggested the use of a vaccination schedule including several doses of PCV13 or association with the PPV23. Since 2013, this combined strategy of PCV13 and PPV23 is recommended by la Haute Autorité de Santé (HAS) for patients at risk, with the following delays: a dose of PCV13 followed by a dose of PPV23, 8 weeks later. We then studied this combined vaccine strategy in patients at risk of IPD: patients with systemic lupus erythematosus (SLE) and patients with rheumatoid arthritis (RA). Our results show a short-term immunogenicity of the combined strategy, but a protection that does not persist beyond two years. Surprisingly, antibody levels 2 years after vaccination are lower than pre-vaccine levels for RA patients. This negative effect of PPV23 on PCV13-induced immune response is called hyporesponsiveness. This phenomenon, observed in RA patients, is not found in SLE patients who received PPV23 vaccination at distance from PCV13. These results suggest that the delayed vaccination schedule (ie, PPV23 vaccination six months after PCV13 instead of two months) could inhibit the hyporesponsiveness phenomenon. In a third study, we compared different vaccine strategies modulating vaccine doses and injection times in healthy volunteers but also in a mouse model of hyporesponsiveness developed in our laboratory. Our hypothesis was that modulation of the vaccine schedule using both vaccines could both induce long-term protection and prevent hyporesponsiveness. Our results showed that decreased doses of PPV23 or concomitant injection of both vaccines did not prevent hyporesponsiveness. However, by increasing the delay between PCV13 and PPV23, the phenomenon of hyporesponsiveness is limited. Clinical studies in patients at risk of IPD are needed to evaluate a delayed combined strategy, where PPV23 would be received at least 6 to 12 months after PCV13

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Ängvard, Mattsson Kerstin. "Anhörigas behov : Stödbehov som anhöriga till patienter med myelom ger uttryck för." Thesis, Uppsala universitet, Institutionen för folkhälso- och vårdvetenskap, 2012. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-175881.

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SAMMANFATTNING Syftet med studien var att undersöka vilka behov av stöd anhöriga till myelompatienter upplever att de har under den polikliniska behandlingsperioden. En kvalitativ metod med deskriptiv design användes och studien utfördes med hjälp av semistrukturerade intervjuer. Nio anhöriga till myelompatienter urvaldes specifikt med tanke på ålder, kön, relation till patienten och hur länge denne varit sjuk. En innehållsanalys av intervjuerna gjordes och de viktigaste fynden i denna studie var att informanterna uttryckte behov av olika typer av information från olika kanaler och att de hade behov av att samtala med någon om sin situation. Efterfrågan på medicinsk information återkom vid olika tillfällen under intervjuerna och det ansågs väsentligt att få veta när förändringar ägde rum i sjukdom och behandling. Informanterna ville ha varierad mängd information, från detaljerad till mer översiktlig sådan och framställan skulle vara muntlig, skriftlig eller både ock. Informanterna angav familj och vänner som samtalspartner men kunde även tänka sig personal och anhöriga till andra patienter. Behov uttrycktes både för att föra samtal enskilt och i grupp, vid varierad tidpunkt. Samtal sågs också som en möjlighet att få uttrycka egna behov och dela andras erfarenheter. Slutsats: Resultatet kan uppmärksamma mottagningar på att de behov av information och samtal som anhöriga ger uttryck för skulle kunna bemötas på ett bättre sätt genom att, på ett tidigt stadium av patientens sjukdom, erbjuda olika former av stöd för att tillgodose dessa behov.
ABSTRACT The aim of the study was to investigate the needs of relatives of patients with myeloma feel that they have during treatment on an outpatient ward. A qualitative approach with a descriptive design was used and the study was performed by doing semi-structured interviews. Nine relatives of patients with myeloma were specifically chosen with regard to age, sex, relationship to the patient and how long he/she had been ill. A content analysis of the interviews were made and the most important findings of this study was that relatives expressed the need for various types of information from various channels and that they had a need to talk to someone about their situation. Demand for medical information returned at different times during the interviews, it was considered essential to know when changes occurred in the illness and treatment. Relatives wanted a varied amount of information, from detailed to more summary and request would be oral, written or both kinds. Relatives specified family and friends as a partner to talk to but could even conceive of staff and relatives to other patients. Need expressed both in order to have talks individually and in groups, at varied times. Talks also were seen as an opportunity to express their needs and share others ' experiences. Conclusion: The result can make outpatient wards to pay attention to the needs for information and talks that relatives expressed could be addressed more effectively by, at an early stage of a patient's illness, provide various forms of assistance to meet these needs.

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Holt, Bronno van der. "Translational studies in elderly patients with acute myeloid leukemia." [S.l.] : Rotterdam : [The Author] ; Erasmus University [Host], 2007. http://hdl.handle.net/1765/10514.

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Holbrook, Felicity Louise. "Generation of patient specific reagents for the study of multiple myeloma tumour progenitor cells." Title page, table of contents and abstract only, 2002. http://web4.library.adelaide.edu.au/theses/09SM/09smh724.pdf.

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"March 2002." Bibliography: leaves 102-117. Hybridoma production was investigated as a means to produce patient specific reagent for the characterisation of putative tumour precursors in multiple myeloma. This work demonstrated the value of phage-displayed peptide libraries for the generation of reagents specific towards myeloma tumour paraproteins.

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PARROCCHETTI, MARIA GRAZIA. "Insuffisance renale aigue sous interferon-alpha chez des patients porteurs d'un myelome multiple." Lille 2, 1993. http://www.theses.fr/1993LIL2M043.

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Ho, Siu-ki, and 何肇騏. "DNA methylation patterns in t(8;21) acute myeloid leukemia patients." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2011. http://hub.hku.hk/bib/B47151389.

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Acute myeloid leukemia (AML) is a heterogeneous disease both clinically and biologically. Approximately 55% of AML harbour karyotypic changes, and one of the most common chromosomal aberrations is the t(8;21)(q22;q22), which leads to the AML1-ETO fusion protein. Previous studies have found that this fusion protein recruits the N-CoR/mSin3A/HDAC complex, thereby acts as a transcriptional repressor. Recently, DNA methylation array studies have shown that DNA methylation patterns can stratify AML cases into different subgroups, and some of these correspond to certain chromosomal abnormalities, such as the t(8;21). These findings suggest a possible link between the fusion transcript AML1-ETO and epigenetic modifications. Additionally, c-kit mutations have emerged as an important disease modifier in the t(8;21) AML and are correlated with poor overall survival and event free survival in patients with t(8;21) AML. We therefore sought to investigate whether there are different DNA methylation patterns in t(8;21) AML with or without c-kit mutations. In our series, 52.2% of the t(8;21) AMLs harbored c-kit mutations, which were correlated with poor event free survival. We next performed pyrosequencing on a selected panel of genes and pinpointed the THBS4 and PAWR genes as hypermethylated in their promoter CpG islands in 86.4% and 59.1% of the t(8;21) AML patients, respectively. These data suggest that THBS4 and PAWR may be important in the pathogenesis of t(8;21) AML.
published_or_final_version
Pathology
Master
Master of Philosophy

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Crossman, Lucy C. "Predictors of imatinib response in patients with chronic myeloid leukaemia." Thesis, University of Newcastle Upon Tyne, 2006. http://hdl.handle.net/10443/1012.

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The majority of patients with chronic myeloid leukaemia (CML) achieve a complete cytogenetic response (CCR) on imatinib. However, we cannot predict which patients will have a suboptimal response. We set out to investigate ways of predicting poor cytogenetic response to imatinib in patients with CML. We examined patients with CML for the possession of particular alleles of the rs2290573 and IL-I P +3953 polymorphisms because these polymorphisms had been linked with the rate of achievement of a major cytogenetic response (MCR). Following the discovery of a polymorphism (K247R) within the P-Ioop of BCR-ABL, we determined its frequency within both CML patients and healthy blood donors, and used in vitro biochemical and cellular assays to test its drug sensitivity. We examined patients with primary cytogenetic resistance to imatinib for the expression of genes associated with drug transport (hOCT 1, MDR 1, ABCG2, ABCCl, ABCA2, ABCC2, ABCC3, ABCC6 and MVP) and compared this to patients who achieved a complete cytogenetic response to imatinib. We used gene expression profiling of CML unselected white cells, and of CML CD34+ cells, to look for genes associated with poor cytogenetic response. We could not find a correlation between the possession of the rs2290573 and IL-I p +3953 polymorphisms, and rate of MCR in our patients. The K247R polymorphism was rare, but 3 out of 5 patients with the arginine allele failed to achieve a major MCR. Despite its position in the P-Ioop, in vitro assays showed K247R to have a drug sensitivity phenotype highly similar to wild type BCR-ABL. Imatini b non-responders had significantly lower pre imatinib gene expression levels of hOCT 1, and significantly higher levels of ABCC3. compared to responders. In addition, in imatinib non-responders we found that the expression level of a variety of drug transport genes changed with time on imatinib, but these changes did not reach statistical significance. Gene expression profiling of CML total white cells revealed that imatinib responders and non-responders had highly similar gene signatures, and that the noise created by different sample source, handling and cell phenotype limited the detection of changes in gene expression. We successfully developed a technique for selecting CD34+ cells from cryopreserved CML mononuclear cells, and preliminary analysis of the CD34+ cell microarray data does not identify any genes that are significantly differentially expressed between cytogenetic responders and non-responders. Possession of the rs2290573 and IL-βI+3953 polymorphisms did not aid prediction of achievement of MCR in our CML popUlation. In patients with CML, possession of the arginine allele of K247R should not be confused with the development of a kinase domain mutation, and the failure of 3 out of 5 patients to achieve a MCR is likely to be a chance finding in a small cohort, but further collection of response data on patients with K247R is required. Differences in drug transport gene expression may influence patients' responses to imatinib, by potentially causing inadequate intracellular imatinib concentrations. Gene expression profiling of CML unselected WBC does not allow prediction of response to imatinib, and work is ongoing to see if the technique proves more useful when using RNA derived from CML CD34+ cells.

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40

Hultqvist, Linda, and Susanne Nilsson. "Patienters upplevelser av att leva med Myelom : Att leva med en tidsinställd bomb." Thesis, Högskolan i Halmstad, Sektionen för hälsa och samhälle (HOS), 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:hh:diva-15291.

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Myelom är en vanlig hematologisk tumörsjukdom med över 500 nya fall varje år i Sverige. Att leva med myelom förändrar de drabbades hela livssituation. Syftet med denna litteraturstudie var att belysa patienters upplevelser av att leva med myelom samt påverkande faktorer. Elva vetenskapliga studier med både kvantitativ och kvalitativ ansats analyserades. Analysen resulterade i tre teman: symtom,symtomkontroll och coping och livskvalitet. Det framkom tydligt i resultatet att det var betydelsefullt att se till patientens hela sammanhang. Många samverkande faktorer påverkar deras upplevelse. Alla delar hör ihop och bildar tillsammans den totala upplevelsen för patienterna med myelom. De levde med en stor osäkerhet och oro kring sin sjukdom. Patienterna upplevde att de oftast var nöjda med informationen de fått, den medicinska vården och vårdpersonalen. Faktorer som trygghet, hopp och vilja att kämpa hade stor betydelse. Resultatet visade också att patienterna med myelom upplevde många skiftande symtom som de försökte hantera på bästa sätt. Symtom som smärta,trötthet och humörsvängningar var det som var vanligast. Det sociala stödet och relationer till närstående var det som var mest betydelsefullt för en god coping och anpassning till livet med myelom. Deras största behov var emotionella och psykosociala. Det skulle vara intressant med fortsatt forskning vad det gäller anhörigas erfarenheter för att därigenom kunna förbättra vardagen för patienterna med myelom.

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41

CABRERA, TEYCHENNE CORINNE, and ANTONIO CABRERA. "Myelome multiple : etude de 127 patients suivis dans le service des maladies du sang du chru d'amiens : premiere partie : etude clinique, biologique et radiologique, classifications - deuxieme partie : evolution et facteurs de pronostic." Amiens, 1990. http://www.theses.fr/1990AMIEM066.

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42

Clarke, Helen Louise. "Evaluation of a patient educational booklet for the management of peripheral neuropathy in multiple myeloma." Thesis, University of the West of England, Bristol, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.557600.

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TITLE: Randomised controlled trial of the efficacy of a patient educational booklet for the management of peripheral neuropathy in multiple myeloma patients. BACKGROUND: As survival improves in multiple myeloma (MM) patients, quality of life and symptom management are becoming paramount. Peripheral neuropathy (PN) is a debilitating side effect of MM and its treatment but can be managed by monitoring symptoms and modifying medication. AIMS: The primary aim of the project was to assess the impact of an educational booklet on knowledge of PN in MM patients. The secondary aim was to assess whether improved knowledge increased the reporting of PN with their HCP leading to better management of PN. METHODS: MM patients diagnosed for at least 1-year were randomised to three treatment groups; group 1 received no information on PN, group 2 & 3 received a PN educational booklet. Questionnaires were completed at 0, 4, 8 and 12-months. Group 1 and 2 completed the questionnaires by themselves whilst group 3 complete their questionnaires via a telephone interview. As group 3 had a high dropout rate during the study period, results from group 2 and 3 participants were combined for the purpose of the study analyses. No significant differences were observed in baseline data between study groups 2 and 3, which enabled the combining of these groups for analysis. RESULTS: Fifty-eight participants were enrolled (19 group 1, 39 group 2 & 3). 63% of participants were male, 67% aged >60 years and 51 % received ~3 prior lines of therapy with at least a third on active treatment at any time point throughout the study. During the course of the study, only 11 % of participants had a resolution of their PN. However, the percentage of participants discussing their PN symptoms at hospital visits significantly declined (p=0.006) over the course of the study, with 96% discussing at baseline vs. 61 % at 12 months. During the course of the study, a significantly higher proportion of participants in group 1 consistently found it a lot more or somewhat more difficult to be optimistic or hopeful about their prognosis and survival when they had PN compared to groups 2 & 3. At baseline, 35% of participants had nothing done to their MM treatment to manage their PN, which increased to 75% at 12-months despite a high number of participants experiencing PN symptoms. In addition, 46% of participants did not receive any treatment recommendations for supplementary medications to manage their PN. The educational booklet was reported as good/very good, easy to understand by virtually all the participants. The most useful section was treatment of PN. Sixty percent of participants think a booklet on PN should be available at diagnosis or at the beginning of their MM treatment with 93% of participants stating that it should be provided by their doctor or nurse. Level of knowledge of PN symptoms, management and reversibility did not significantly change in either of the treatment groups. However, participants in groups 2 & 3 demonstrated a positive change in their beliefs of the management of PN indicating that the booklet provided may have had a positive (if small) impact on knowledge. Conversely, group 1 participants reported a small decline in their beliefs on the management of PN over the course of the study. SUMMARY/CONCLUSIONS: The educational booklet had no significant impact on knowledge however; there was a positive change in beliefs of the management and reversibility of PN in the participants who received the booklet. The study results indicate that overall, PN in MM patients is not currently being adequately managed through modification of the MM therapy and/or additional treatment recommendations. Future work needs to be conducted to evaluate methods to improve the communication between healthcare professionals and MM patients to ensure consistently high levels of discussion on PN take place pre, during and post MM treatment to help drive an improvement in the management of PN.

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43

Schmidt, Henner. "Die operative Therapie skelettaler Komplikationen bei Patienten mit multiplem Myelom." Diss., lmu, 2012. http://nbn-resolving.de/urn:nbn:de:bvb:19-144838.

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44

Johnson, Peter R. E. "The biology and treatment of acute myeloid leukaemia in elderly patients." Thesis, University of Aberdeen, 1992. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.306856.

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Acute myeloid leukaemia (AML) is predominantly a disease of the elderly; the median age is 64 years and almost 60% of cases are over 60 years old. Unfortunately however, the treatment of AML in elderly patients is generally unsatisfactory with significantly poorer remission rates and overall survival than in younger patients. We have designed a novel treatment regimen consisting of Mitozantrone and Cytosine Arabinoside specifically for elderly patients and have evaluated the regimen in 104 patients over 60 years old in the North West region. The complete remission rate was 58%, the median duration of remission was 11 months and the median survival was 9 months. These results compare very favourably with previous reports in elderly patients. The regimen was associated with tolerable toxicity and a gratifying improvement in the performance status of responders. Extensive univariate and mutivariate analysis of data arising from the study has been performed, and models to predict outcome of therapy and overall survival have been performed. The latter model may be particularly useful in assisting the identification of elderly patients who would benefit from intensive chemotherapy. The biology of AML in elderly patients has been studied with particular emphasis on morphology, cytogenetic abnormalities and in-vitro culture patterns. Compared with younger patients, cases of AML in the elderly have a high incidence of clinical and morphological myelodysplasia, frequently have prognostically adverse chromosomal abnormalities and have reduced in-vitro cloning efficiency. Thus intrinsic differences in the biology of AML in the elderly have been demonstrated which may, in part, account for the adverse prognosis of AML in elderly patients. The impact of new technologies upon the treatment of AML in the elderly is discussed with particular emphasis on the haemopoietic growth factors and new techniques for studying leukaemia biology.

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45

Sellar, R. S. "Investigation of cell cycle status in patients with acute myeloid leukaemia." Thesis, University College London (University of London), 2018. http://discovery.ucl.ac.uk/10041751/.

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Acute myeloid leukaemia (AML) is a biologically and clinically heterogeneous disease. Studies investigating heterogeneity in cell cycle status and response to treatment have been inconsistent, did not take into account the molecular features of the disease, and used blasts derived from aspirates (BMA) or peripheral blood (PB). The work in this thesis used the expression of the DNA replication licensing factors MCM2 (positive in non-G0 cells) geminin (positive in S/G2/M phase) in combination with MIB-1 (actively cycling cells) as assessed by immunohistochemistry and immunocytochemistry to define the cell cycle status of the blasts from PB, BMA, and biopsies (BMT). It shows that the majority of blasts in PB exist in a G1-arrested state and these blasts cause results derived from BMA or PB to significantly underestimate disease proliferation. Further experiments using flow cytometry and RNA sequencing support these conclusions and demonstrate that accurate assessment of cell cycle status in patients requires the use of BMT. A cohort of 181 patients with AML and available BMT for the assessment of DNA replication licensing factors was identified and defined for clinical, cytogenetic, and molecular features, and clinical outcome. The features of this cohort were consistent with those from large clinical trials. Increased expression of geminin and higher geminin/MIB-1 ratios (increased speed of cycling) were associated with NPM1 mutations and improved response to induction therapy in both univariate and multivariate analysis. Patients with lower geminin/MIB-1 ratios had increased rates of relapse and, in a landmark analysis from the second cycle of treatment, a trend towards inferior overall survival. These results suggest a mechanism for the improved response and decreased relapse risk seen in patients with NPM1 mutations and the potential clinical utility of examining DNA replication licensing factors.

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46

Hummert, Shelly, and Myke R. Green. "Therapeutic Drug Monitoring and Dose Adjustment of Posaconazole in Adult Patients with Acute Myeloid Leukemia: A Single-Center Experience." The University of Arizona, 2014. http://hdl.handle.net/10150/614191.

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Class of 2014 Abstract
Specific Aims: Evaluate serum posaconazole concentrations following dose adjustment in response to subtherapeutic serum concentrations. Determine optimal dose adjustment schema and identify toxicity with doses above 600 mg daily (e.g.: 200 mg per os three times daily). Methods: The health records were reviewed for 29 patients ≥ 18 years with acute myeloid leukemia over a four-year period. Participants initially received posaconazole 200 mg per os three times daily as prophylaxis and required at least one dose adjustment secondary to a subtherapeutic posaconazole serum concentration. Patients were stratified by posaconazole dosing following dose adjustment (A=200mg QID, B=300mg TID, C=400 mg TID, D=400 QID). Main Results: There was a statistically significant increase in posaconazole serum concentration in each group compared to baseline serum concentration, aside from group C (group A and B P<0.001, group C P=0.236, and group D P=0.0076). The majority of participants in 3 of the 4 groups reached therapeutic serum concentration (A=0.87, B=0.76, D=0.80) whereas group C had a serum posaconazole concentration on average below therapeutic range (0.51). There was no significant difference between the four groups in regards to renal function (p=0.35) or hepatic function (AST p=0.676, ALT p=0.877, total bilirubin p=0.097). Conclusion: A dose increase led to an increase in posaconazole serum concentration except for the dosing regimen of 400 mg three times daily. However, the study is limited by a small patient population, an unequal number of patients in each group, and potentially by poor absorption of posaconazole suspension. Further research is required to expand on these findings.

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CARCASSET, GUILBERT SYLVIE. "Imagerie par resonance magnetique nucleaire de la moelle osseuse des myelomes multiples : etude a propos de 59 patients." Lille 2, 1994. http://www.theses.fr/1994LIL2M110.

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48

Kottaridis, Panagiotis. "Investigations of FLT3 internal tandem duplications in patients with acute myeloid leukaemia." Thesis, University College London (University of London), 2006. http://discovery.ucl.ac.uk/1444905/.

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In acute myeloid leukaemia (AML), further prognostic determinants are required in addition to cytogenetics to predict patients at increased risk of relapse. Recent studies have indicated an internal tandem duplication (ITD) in the FLT3 gene may adversely affect clinical outcome. The studies reported in this thesis evaluated the impact of a FLT3/ITD on outcome in 854 patients treated in UK MRC AML trials. A FLT3/ITD was present in 27% patients and was associated with leucocytosis and a high percentage of bone marrow blast cells. With respect to clinical outcome it predicted for increased relapse risk (RR), adverse disease-free survival (DFS), event-free survival (EFS) and overall survival (OS). In multivariate analysis, presence of a mutation was the most significant prognostic factor predicting for RR and DFS. In order to evaluate whether FLT3 mutations can be used as markers of minimal residual disease, paired presentation and relapse samples were studied. Twenty four patients were wild type FLT3 at diagnosis and 4 acquired a FLT3 mutation at relapse. Of 20 patients positive at diagnosis, 5 who were all originally ITD+, had no detectable mutation at relapse. Furthermore, another patient had a completely different ITD at relapse which could not be detected in the presentation sample. These results suggest that, at least in some patients, FLT3 mutations are secondary events in leukaemogenesis, are unstable and thus should be used cautiously for the detection of minimal residual disease. Given the high frequency of activating FLT3 mutations in patients with AML, FLT3 and its downstream pathway are attractive targets for directed inhibition. Several promising tyrosine kinase inhibitors have recently been identified and in vitro data reported here suggest that FLT3 inhibitors may have a role either as monotherapy or in combination with conventional cytotoxic agents in the treatment of AML.

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Huang, Yidi. "Comprehensive Computational Analysis of Disease-site Microbiome in Patients with Myeloid Malignancy." Case Western Reserve University School of Graduate Studies / OhioLINK, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=case1575466186675208.

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50

Beaver, Melissa A. "A Secondary Analysis of Imatinib Adherence Among Patients with Chronic Myeloid Leukemia." Thesis, The University of Arizona, 2010. http://hdl.handle.net/10150/156890.

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Background: Two recent studies have identified a strong association between treatment adherence and treatment response in patients with chronic myeloid leukemia (CML) treated with imatinib; and suggested a possible 7-10% tolerance margin for nonadherence before impaired treatment response is likely to occur. Objective: To determine at what percentage of dosing adherence of imatinib impaired treatment response (suboptimal response of incomplete cytogenetic response is likely to occur; and, conversely, at what percent of dosing adherence positive treatment response is likely to ensue CML patients.

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Dissertations / Theses on the topic 'Myeloma patients'

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