Survival patterns among lymphoma patients with a family history of lymphoma

Purpose: Genetic factors are important in the etiology and pathogenesis of chronic lymphocytic leukemia (CLL), Hodgkin's lymphoma (HL), and non-Hodgkin's lymphoma (NHL). Only a few small studies have assessed clinical characteristics and prognosis for familial patients, with inconsistent findings. Methods: Using population-based registries from Sweden and Denmark, 7,749 patients with CLL, 7,476 patients with HL, and 25,801 patients with NHL with linkable first-degree relatives were identified. Kaplan-Meier curves were constructed to compare survival in patients with lymphoma with and without a family history of lymphoma. The risk of dying was assessed using adjusted Cox proportional hazard models. Results: We found 85 patients with CLL (1.10%), 95 patients with HL (1.28%), and 206 patients with NHL (0.80%) with a family history of any lymphoma. Five-year mortality was similar for patients with CLL (hazard ratio [HR], 1.28; 95% CI, 0.95 to 1.72), HL (HR, 0.78; 95% CI, 0.49 to 1.25), and NHL (HR, 0.91; 95% CI, 0.74 to 1.12) versus without a family history of any lymphoma. Mortality was also similar for patients with versus without a family history of the same lymphoma. T-cell/anaplastic lymphoma patients with a family history of NHL had poorer outcome 5-years after diagnosis (HR, 5.38; 95% CI, 1.65 to 17.52). Results were similar for 10 years of follow-up. Conclusion: With the exception of T-cell/anaplastic lymphoma, survival patterns for patients with CLL, HL, and NHL with a family history of lymphoma were similar to those for sporadic patients, suggesting that most familial lymphomas do not have an altered clinical course. Our findings provide no evidence to modify therapeutic strategies for patients with CLL, HL, or NHL based solely on family history. © 2008 by American Society of Clinical Oncology.


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ABCB1 (MDR1) rs1045642 is associated with increased overall survival in plasma cell myeloma

Multi-drug resistance (MDR) may compromise the successful management of haematological malignancies, impairing the effectiveness of chemotherapy. The P-glycoprotein (P-gp) drug efflux pump, encoded by the gene ABCB1 (MDR1), is the most widely studied component in MDR. A single nucleotide polymorphism (SNP) has been identified within ABCB1, rs1045642 (C3435T), which may alter P-gp substrate specificity and have an impact on the effectiveness of treatment, and hence overall survival (OS). We estimated the frequency of this SNP in the Northern Irish population and investigated its impact on the OS of patients with plasma cell myeloma (PCM). There was no significant difference in the frequency of rs1045642 between the PCM cohort and an age- and gender-matched control population. Findings within the PCM cohort suggest that rs1045642 genotype influences OS (p = 2 x 10(-2)). If confirmed in larger studies, these results suggest that genotyping rs1045642 may be a useful predictor of outcome in PCM and could indicate modified treatment modalities in certain individuals.

Gamma ray-induced bystander effect in tumour glioblastoma cells: a specific study on cell survival, cytokine release and cytokine receptors.

Recent experimental evidence has challenged the paradigm according to which radiation traversal through the nucleus of a cell is a prerequisite for producing genetic changes or biological responses. Thus, unexposed cells in the vicinity of directly irradiated cells or recipient cells of medium from irradiated cultures can also be affected. The aim of the present study was to evaluate, by means of the medium transfer technique, whether interleukin-8 and its receptor (CXCR1) may play a role in the bystander effect after gamma irradiation of T98G cells in vitro. In fact the cell specificity in inducing the bystander effect and in receiving the secreted signals that has been described suggests that not only the ability to release the cytokines but also the receptor profiles are likely to modulate the cell responses and the final outcome. The dose and time dependence of the cytokine release into the medium, quantified using an enzyme linked immunosorbent assay, showed that radiation causes alteration in the release of interleukin-8 from exposed cells in a dose-independent but time-dependent manner. The relative receptor expression was also affected in exposed and bystander cells.

Habitat for Humanity: Calibrating Best Practice Against the MDGs

Poverty alleviation lies at the heart of contemporary international initiatives on development. The key to development is the creation of an environment in which people can develop their potential, leading productive, creative lives in accordance with their needs, interests and faith. This entails, on the one hand, protecting the vulnerable from things that threaten their survival, such as inadequate nutrition, disease, conflict, natural disasters and the impact of climate change, thereby enhancing the poor’s capabilities to develop resilience in difficult conditions. On the other hand, it also requires a means of empowering the poor to act on their own behalf, as individuals and communities, to secure access to resources and the basic necessities of life such as water, food, shelter, sanitation, health and education. ‘Development’, from this perspective, seeks to address the sources of human insecurity, working towards ‘freedom from want, freedom from fear’ in ways that empower the vulnerable as agents of development (not passive recipients of benefaction).

Recognition of the magnitude of the problems confronted by the poor and failure of past interventions to tackle basic issues of human security led the United Nations (UN) in September 2000 to set out a range of ambitious, but clearly defined, development goals to be achieved by 2015. These are known as the Millennium Development Goals (MDGs). The intention of the UN was to mobilise multilateral international organisations, non-governmental organisations and the wider international community to focus attention on fulfilling earlier promises to combat global poverty. This international framework for development prioritises: the eradication of extreme poverty and hunger; achieving universal primary education; promoting gender equality and empowering women; reducing child mortality; improving maternal health; combating HIV/AIDS, malaria and other diseases; ensuring environmental sustainability; and developing a global partnership for development. These goals have been mapped onto specific targets (18 in total) against which outcomes of associated development initiatives can be measured and the international community held to account. If the world achieves the MDGs, more than 500 million people will be lifted out of poverty. However, the challenges the goals represent are formidable. Interim reports on the initiative indicate a need to scale-up efforts and accelerate progress.
Only MDG 7, Target 11 explicitly identifies shelter as a priority, identifying the need to secure ‘by 2020 a significant improvement in the lives of at least 100 million slum dwellers’. This raises a question over how Habitat for Humanity’s commitment to tackling poverty housing fits within this broader international framework designed to allievate global poverty. From an analysis of HFH case studies, this report argues that the processes by which Habitat for Humanity tackles poverty housing directly engages with the agenda set by the MDGs. This should not be regarded as a beneficial by-product of the delivery of decent, affordable shelter, but rather understood in terms of the ways in which Habitat for Humanity has translated its mission and values into a participatory model that empowers individuals and communities to address the interdependencies between inadequate shelter and other sources of human insecurity. What housing can deliver is as important as what housing itself is.

Examples of the ways in which Habitat for Humanity projects engage with the MDG framework include the incorporation of sustainable livelihoods strategies, up-grading of basic infrastructure and promotion of models of good governance. This includes housing projects that have also offered training to young people in skills used in the construction industry, microfinanced loans for women to start up their own home-based businesses, and the provision of food gardens. These play an important role in lifting families out of poverty and ensuring the sustainability of HFH projects. Studies of the impact of improved shelter and security of livelihood upon family life and the welfare of children evidence higher rates of participation in education, more time dedicated to study and greater individual achievement. Habitat for Humanity projects also typically incorporate measures to up-grade the provision of basic sanitation facilities and supplies of safe, potable drinking water. These measures not only directly help reduce mortality rates (e.g. diarrheal diseases account for around 2 million deaths annually in children under 5), but also, when delivered through HFH project-related ‘community funds’, empower the poor to mobilise community resources, develop local leadership capacities and even secure de facto security of tenure from government authorities.

In the process of translating its mission and values into practical measures, HFH has developed a range of innovative practices that deliver much more than housing alone. The organisation’s participatory model enables both direct beneficiaries and the wider community to tackle the insecurities they face, unlocking latent skills and enterprise, building sustainable livelihood capabilities. HFH plays an important role as a catalyst for change, delivering through the vehicle of housing the means to address the primary causes of poverty itself. Its contribution to wider development priorities deserves better recognition. In calibrating the success of HFH projects in terms of units completed or renovated alone, the significance of the process by which HFH realises these outcomes is often not sufficiently acknowledged, both within the organisation and externally. As the case studies developed in the report illustrate, the methodologies Habitat for Humanity employs to address the issue of poverty housing within the developing world, place the organisation at the centre of a global strategic agenda to address the root causes of poverty through community empowerment and the transformation of structures of governance.

Given this, the global network of HFH affiliates constitutes a unique organisational framework to faciliate sharing resources, ideas and practical experience across a diverse range of cultural, political and institutional environments. This said, it is apparent that work needs to be done to better to faciliate the pooling of experience and lessons learnt from across its affiliates. Much is to be gained from learning from less successful projects, sharing innovative practices, identifying strategic partnerships with donors, other NGOs and CBOs, and engaging with the international development community on how housing fits within a broader agenda to alleviate poverty and promote good governance.