This study examines the influence social support has on delay of treatment among African-American lymphoma patients. One hundred nineteen (119) social work assessments were collected from medical records utilizing non-probability sampling. Data were extracted from the social work assessments of lymphoma patients considered for or having had bone marrow transplantation. The measurement tool was designed based on survey information from the Supportive Care Needs Survey, Social Support Behaviors Scale and the Social Support Survey Instrument. The findings of the study indicated that, overall, social support did not significantly influence delay of treatment. However, there were statistically significant relationships among social worker support and delay, gender and delay, and type of lymphoma diagnosis and delay for bone marrow transplantation. A large percentage of the patient population who may have been considered for bone marrow transplantation did not receive social work assessments and could have experienced delay associated with limited social support. Further research should be conducted on why this population did not receive social work assessments and comparisons should be made to the population that did in order to examine group differences

Tumour associated macrophages (TAMs) have been associated with prognosis in a wide variety of tumours with most studies showing a high number of macrophages equating with poor prognosis. This is postulated to be due to TAMs providing support to the tumour through a wide variety of mechanisms including suppression of the immune response, promotion of angiogenesis and provision of growth supporting signals. Previous work within the group has characterised some of the mechanisms by which Burkitt lymphoma cells attract macrophages to the tumour and some of the mechanisms by which these macrophages support tumour cell growth. This thesis extends some of the work carried out in Burkitt lymphoma to Diffuse Large B cell lymphoma (DLBCL) and examines TAMs in this tumour type. Diffuse Large B cell lymphoma is the commonest high grade lymphoma in the Western world. Like Burkitt lymphoma it is characterised by diffuse sheets of lymphoid blasts. In contrast to Burkitt lymphoma, it represents a less well-defined entity that encompasses tumours with variable morphology, genetic abnormalities and outcome. Rates of proliferation and apoptosis vary between individual tumours, and unlike Burkitt lymphoma not all cases are characterised by a prominent macrophage infiltrate. Previous work within the group has shown a relationship in Burkitt lymphoma between apoptosis, macrophage infiltration and proliferation suggesting that apoptosis recruits macrophages to provide support to the tumour cells. This relationship was studied here in a large cohort of patients with DLBCL and the same relationship shown to exist in this tumour also. Following this observation, a bioinformatic approach was taken to define a gene expression signature of the TAM in DLBCL in situ in an unbiased way. Using large publicly available human tumour gene expression datasets, a graph clustering approach using the tool Biolayout Express 3D was used to explore the transcriptome of DLCBL and other human tumours. Signatures of immune cells and stromal cells, functional pathways and tumour specific signatures were defined from individual tumour type transcriptomes by study of clusters of co-expressed genes. Further work used a novel graph clustering approach based on mean Pearson correlations to define a ‘core’ transcriptome signature shared across many unrelated tumour types and in which elements of the tumour stroma were prominent. To validate the TAM signature derived from the DLBCL dataset, protein expression of selected elements of the signature were analysed at the protein level by immunohistochemistry in an unrelated cohort of DLBCL. Selected markers from the DLBCL TAM signature were then assessed for relationship to outcome in a cohort of patients treated with CHOP chemotherapy. Of the proteins studied, a significant difference in outcome was demonstrated only for leukocyte associated immunoglobulin receptor 1 (LAIR1) expression by TAMs, where low intensity staining for LAIR1 in TAMs was associated with better overall survival. LAIR1 is a collagen-binding inhibitory receptor expressed only in cells of haemopoetic lineage whose role is little studied in macrophages. The final results chapter presents some preliminary data from co-culture experiments in which the expression of LAIR-1 on the ‘macrophage-like’ cell line THP-1 is studied in various polarisation states and the ability of these cells to support or constrain tumour cell growth studied in the presence or absence of collagen.

[20] 172 [45] leaves : / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (M.D. 1974) from the Dept. of Medicine, University of Adelaide

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2009. / Härtill 4 uppsatser.

This thesis employed methods used in health care decision making to evaluate strategies for prevention and treatment of febrile neutropenia (FN) in non-Hodgkin lymphoma (NHL) patients. The objectives of this thesis were to quantify the cost-effectiveness of filgrastim and pegfilgrastim as primary prophylaxis against FN in NHL patients, to develop an algorithm for converting health-related quality of life data collected in non-Hodgkin lymphoma patients into preference-based health utility values, and to evaluate NHL patients’ preferences for outpatient treatment of FN. The cost-effectiveness analysis demonstrated that neither filgrastim, nor pegfilgrastim are cost-effective, with respective incremental cost-effectiveness ratios [95% confidence interval] of $4,599,000/QALY [$597,045, dominated] and $6,272,000/QALY [$730,692, dominated], well above the normally accepted threshold of $50,000/QALY. The algorithm for deriving health utility values was based on a regression model that used health utility values obtained from the EQ-5D instrument as the outcome variable and the four subscales of the Functional Assessment of Cancer Therapy – General (FACT-G) questionnaire as the predictor variables. The model final model included three of the FACT-G subscales, and had an R-squared value of 0.502 and a mean squared error of 0.013. A discrete choice experiment was used to examine patients’ preferences for out patient treatment of FN, and demonstrated that out-of-pocket costs, unpaid caregiver time required daily, and probability of return to hospital are all significant attributes when considering outpatient therapy for FN. Adjusted odds ratios [95% confidence intervals] of accepting outpatient treatment for FN were 0.84 [0.75 to 0.95] for each $10 increase in out-of-pocket cost; 0.82 [0.68 to 0.99] for each 1 hour increase in daily unpaid caregiver time; and 0.53 [0.50 to 0.57] for each 5% increase in probability of return to hospital. These results provide important information for clinicians and health care decision makers involved in implementing programs for NHL patients with FN.

This thesis employed methods used in health care decision making to evaluate strategies for prevention and treatment of febrile neutropenia (FN) in non-Hodgkin lymphoma (NHL) patients. The objectives of this thesis were to quantify the cost-effectiveness of filgrastim and pegfilgrastim as primary prophylaxis against FN in NHL patients, to develop an algorithm for converting health-related quality of life data collected in non-Hodgkin lymphoma patients into preference-based health utility values, and to evaluate NHL patients’ preferences for outpatient treatment of FN. The cost-effectiveness analysis demonstrated that neither filgrastim, nor pegfilgrastim are cost-effective, with respective incremental cost-effectiveness ratios [95% confidence interval] of $4,599,000/QALY [$597,045, dominated] and $6,272,000/QALY [$730,692, dominated], well above the normally accepted threshold of $50,000/QALY. The algorithm for deriving health utility values was based on a regression model that used health utility values obtained from the EQ-5D instrument as the outcome variable and the four subscales of the Functional Assessment of Cancer Therapy – General (FACT-G) questionnaire as the predictor variables. The model final model included three of the FACT-G subscales, and had an R-squared value of 0.502 and a mean squared error of 0.013. A discrete choice experiment was used to examine patients’ preferences for out patient treatment of FN, and demonstrated that out-of-pocket costs, unpaid caregiver time required daily, and probability of return to hospital are all significant attributes when considering outpatient therapy for FN. Adjusted odds ratios [95% confidence intervals] of accepting outpatient treatment for FN were 0.84 [0.75 to 0.95] for each $10 increase in out-of-pocket cost; 0.82 [0.68 to 0.99] for each 1 hour increase in daily unpaid caregiver time; and 0.53 [0.50 to 0.57] for each 5% increase in probability of return to hospital. These results provide important information for clinicians and health care decision makers involved in implementing programs for NHL patients with FN.

No description available.

Diss. (sammanfattning) Uppsala : Sveriges lantbruksuniv., 2003. / Härtill 3 uppsatser.

A well-functioning immune system is of paramount importance in preventing lymphomagenesis. Both immunostimulation, which causes excessive cell turnover and increased potential for mutations, and immunosuppression, causing a decreased ability to monitor and halt aberrant cell proliferation, have been implicated in cancer development. Autoimmune diseases are characterized by excessive activation of lymphocytes due to a dysregulated response to self-antigens. The treatments for autoimmune disease therefore share a common goal of immunosuppression. While treatments have become better-targeted to specific inflammatory pathways over the last 30 years as opposed to general immunosuppression, there remains a high risk of hematologic malignancy for patients with autoimmune disease relative to the general population. There are numerous types of autoimmune disease, as well as much heterogeneity within each diagnosis from patient to patient. The focus of this thesis is Rheumatoid Arthritis (RA), a strikingly common disease affecting 0.5-1.0% of the world population and characterized by debilitating, painful, joint-deforming symptoms and difficulty in achieving remission. [1] Therapeutic intervention often necessitates a trial and error approach and various combinations of drugs, in the same way cocktails of chemotherapeutic drugs are tailored to treat cancers due to their heterogeneity. Drugs for the treatment of autoimmune diseases are collectively known as Disease-Modifying Anti-Rheumatic Drugs (DMARDs) and were only first widely used for the treatment of RA in the 1980s. This short history of widespread use, along with the great variability in manifestation of disease and treatment course, has historically limited the ability of observational studies to determine the safety of DMARDs in terms of malignancy risk. Only in the past few years has enough information been available, drawn mostly from national healthcare databases in several countries, to enable strong conclusions about the effects of DMARDs on malignancy risk. This thesis aims to provide a comprehensive review of the most recent and well-designed studies regarding currently available DMARDs for RA and their effects on the risk of lymphoma.

Class of 2017 Abstract / This project is related to the article that was later published, available at this link: https://doi.org/10.1016/j.critrevonc.2016.11.009 / Objectives: Brentuximab vedotin (BV) is an antibody-drug conjugate comprising a CD30-directed antibody conjugated to the microtubule-disrupting agent MMAE via a protease cleavable linker. BV is FDA approved for use in relapsed classical Hodgkin lymphoma and relapsed systemic Methods: primary study outcomes being objective response rate. PubMed (1946-2015), EMBASE (1947-2015), and Cochrane Central Register of Controlled Trials (1898-2015). Inclusion criteria included all studies and case reports of NHLs in which BV therapy was administered. Twenty-eight articles met these criteria. Results: Utilizing the twelve clinical subtypes, we found clinical evidence of BV and stratified the study populations into three groups: B-cell malignancies (group A), T-cell malignancies (group B), and non-B or non-T-cell hematological malignancies (group C). Across the group A malignancies, there were 87 patients. 48% experienced an objective response (OR). Across the group B malignancies, there were 274 patients. 74% experienced an OR. Across the group C malignancies, there were 9 patients. 44% experienced an OR. Conclusions: Our findings indicate that BV induces a variety of responses, largely positive and variable between NHL subtypes. With properly powered prospective studies, BV may prove to be a strong candidate in the treatment of CD30+ malignancies.