Long-Term Outcomes of Autologous Stem Cell Transplantation for Follicular Non-Hodgkin Lymphoma: Effect of Histological Grade and Follicular International Prognostic Index

AbstractAlthough results of autologous stem cell transplantation (SCT) for recurrent follicular non-Hodgkin lymphoma (NHL) have been previously reported, the long-term results and evaluation of prognostic factors in a large patient population receiving this therapy are difficult to find in the literature. To address these issues, we evaluated 248 patients with recurrent follicular NHL treated with high-dose chemotherapy and autologous SCT between 7/87 and 6/03. According to the World Health Organization (WHO) classification system, 64 patients (26%) had follicular NHL grade 1 (FL 1), 98 (40%) had FL 2, and 86 (35%) had FL 3. At the time of transplantation, 88 of the patients (35%) had a Follicular Lymphoma International Prognostic Index (FLIPI) score of low risk, 87 (35%) had an intermediate-risk FLIPI score, 37 (15%) had a high-risk FLIPI score, and 36 (15%) had at least 1 missing value, preventing calculation of the FLIPI score. The 5-year overall survival (OS) for all patients was 63%, and the 5-year progression-free survival (PFS) was 44%. In a multivariate analysis, a histological grade of FL 3, a high-risk FLIPI score at the time of transplantation, and having received 3 or more previous chemotherapy regimens were significant factors for predicting a worse OS. In addition, the use of a transplantation regimen including a monoclonal antibody decreased the relative risk of progressive lymphoma. These data suggest that transplantation earlier in the course of the disease for patients with follicular lymphoma with use of a monoclonal antibody–based regimen may lead to improved outcomes

Genetic algorithm dynamics on a rugged landscape

The genetic algorithm is an optimization procedure motivated by biological evolution and is successfully applied to optimization problems in different areas. A statistical mechanics model for its dynamics is proposed based on the parent-child fitness correlation of the genetic operators, making it applicable to general fitness landscapes. It is compared to a recent model based on a maximum entropy ansatz. Finally it is applied to modeling the dynamics of a genetic algorithm on the rugged fitness landscape of the NK model.Comment: 10 pages RevTeX, 4 figures PostScrip

A matter of divergence: Tracking recent warming at hemispheric scales using tree ring data

No current tree ring (TR) based reconstruction of extratropical Northern Hemisphere (ENH) temperatures that extends into the 1990s captures the full range of late 20th century warming observed in the instrumental record. Over recent decades, a divergence between cooler reconstructed and warmer instrumental large-scale temperatures is observed. We hypothesize that this problem is partly related to the fact that some of the constituent chronologies used for previous reconstructions show divergence against local temperatures in the recent period. In this study, we compiled TR data and published local/regional reconstructions that show no divergence against local temperatures. These data have not been included in other large-scale temperature reconstructions. Utilizing this data set, we developed a new, completely independent reconstruction of ENH annual temperatures (1750–2000). This record is not meant to replace existing reconstructions but allows some degree of independent validation of these earlier studies as well as demonstrating that TR data can better model recent warming at large scales when careful selection of constituent chronologies is made at the local scale. Although the new series tracks the increase in ENH annual temperatures over the last few decades better than any existing reconstruction, it still slightly under predicts values in the post-1988 period. We finally discuss possible reasons why it is so difficult to model post-mid-1980s warming, provide some possible alternative approaches with regards to the instrumental target and detail several recommendations that should be followed in future large-scale reconstruction attempts that may result in more robust temperature estimates

How to make predictions about future infectious disease risks

Formal, quantitative approaches are now widely used to make predictions about the likelihood of an infectious disease outbreak, how the disease will spread, and how to control it. Several well-established methodologies are available, including risk factor analysis, risk modelling and dynamic modelling. Even so, predictive modelling is very much the ‘art of the possible’, which tends to drive research effort towards some areas and away from others which may be at least as important. Building on the undoubted success of quantitative modelling of the epidemiology and control of human and animal diseases such as AIDS, influenza, foot-and-mouth disease and BSE, attention needs to be paid to developing a more holistic framework that captures the role of the underlying drivers of disease risks, from demography and behaviour to land use and climate change. At the same time, there is still considerable room for improvement in how quantitative analyses and their outputs are communicated to policy makers and other stakeholders. A starting point would be generally accepted guidelines for ‘good practice’ for the development and the use of predictive models

Phase I/II Study of Bortezomib-BEAM and Autologous Hematopoietic Stem Cell Transplantation for Relapsed Indolent Non-Hodgkin Lymphoma, Transformed, or Mantle Cell Lymphoma

AbstractA phase I/II trial was designed to evaluate the safety and efficacy of adding bortezomib to standard BEAM (BCNU, etoposide, cytarabine, melphalan) and autologous hematopoietic stem cell transplantation (ASCT). Eligible patients had relapsed/refractory indolent or transformed non-Hodgkin lymphoma or mantle cell lymphoma (MCL) that was relapsed/refractory or in first partial (PR) or complete remission (CR). Patients received bortezomib on days −11, −8, −5, and −2 before ASCT. Phase I had 4 dose cohorts (.8, 1, 1.3, and 1.5 mg/m2) and 3 patients were accrued to each. Any nonhematological ASCT-related toxicity >2 on the Bearman scale occurring between day −11 and engraftment defined the maximum tolerated dose (MTD). After the MTD has been reached, another 20 patients were enrolled at this dose to determine a preliminary overall response rate (ORR). Patients who were in CR or PR at day +100 were considered responders. The study enrolled 42 patients through August 14, 2009. The median age was 58 (range, 34 to 73) years, with 33 males and 9 females. The most common diagnoses were MCL (23 patients) and follicular lymphoma (7 patients). The median number of prior therapies was 1 (range, 0 to 6). The median follow-up was 4.88 (range, 1.07 to 6.98) years. Thirteen patients were treated in phase I and 29 patients were treated in phase II. The MTD was initially determined to be 1.5 mg/m2 but it was later decreased to 1 mg/m2 because of excessive gastrointestinal toxicity and peripheral neuropathy. The ORR was 95% at 100 days and 87% at 1 year. For all 38 evaluable patients at 1 year, responses were CR 84%, PR 1%, and progressive disease 13%. Progression-free survival (PFS) was 83% (95% CI, 68% to 92%) at 1 year, and 32% (15% to 51%) at 5 years. Overall survival (OS) was 91% (95% CI, 79% to 96%) at 1 year and 67% (50% to 79%) at 5 years. The most common National Cancer Institute grade 3 toxicities were neutropenic fever (59%), anorexia (21%), peripheral neuropathy (19%), orthostatic hypotension/vasovagal syncope (16%), and 1 patient failed to engraft. Compared with 26 MCL in CR1 historic controls treated with BEAM and ASCT, PFS was 85% and 43% for the BEAM group versus 87% and 57% for those who received bortezomib in addition to standard BEAM (V-BEAM) at 1 and 5 years, respectively (log-rank P = .37). OS was 88% and 50% for the BEAM group versus 96% and 72% for V-BEAM at 1 and 5 years, respectively (log-rank P = .78). In conclusion, V-BEAM and ASCT is feasible. The toxicities were manageable and we did not observe any treatment-related mortalities; however, we did observe an excess of autonomic dysfunction and ileus, which is concerning for overlapping toxicity with BEAM conditioning. Determining relative efficacy of V-BEAM compared to BEAM would require a randomized trial

Supporting multiattribute decisions in scenario planning using a simple method based on ranks

A neglected area of scenario planning is the provision of support for strategic decisions that involve multiple attributes. When the number of scenarios and attributes is large, conventional multiattribute decision analysis methods require the elicitation of a large number of values and weights, which can be demanding and time consuming for decision makers. This paper examines the effectiveness of using a simple approximation to the simple multiattribute rating method (SMART) that is based purely on the ranking of options and attributes. The method was tested on 250,000 simulated decision problems and was found to perform well when assessed on the basis of its hit rate (the percentage of times it identified the same best option as SMART) and the utility loss resulting from the approximation. In large problems, where simplifications are likely to be most useful, it outperformed an alternative approximation method, SMARTER, which is more complex to apply, and it was almost as effective as SMARTER on smaller problems

Topographic and ecologic controls on root reinforcement

Shallow landslides are a significant hazard in steep, soil-mantled landscapes. During intense rainfall events, the distribution of shallow landslides is controlled by variations in landscape gradient, the frictional and cohesive properties of soil and roots, and the subsurface hydrologic response. While gradients can be estimated from digital elevation models, information on soil and root properties remains sparse. We investigated whether geomorphically controlled variations in ecology affect the spatial distribution of root cohesion by measuring the distribution and tensile strength of roots from soil pits dug downslope of 15 native trees in the southern Appalachian Mountains, North Carolina, United States. Root tensile strengths from different hardwood tree species were similar and consistently higher than the only native shrub species measured (Rhododendron maximum). Roots were stronger in trees found on noses (areas of divergent topography) relative to those in hollows (unchanneled, convergent topography) coincident with the variability in cellulose content. This cellulose variability is likely related to topographic differences in soil water potential. For all species, roots were concentrated close to the soil surface, with roots in hollows being more evenly distributed in the soil column than those on noses. Trees located on noses had higher mean root cohesion than those in hollows because of a higher root tensile force. R. maximum had the shallowest, weakest roots suggesting that recent expansion of this species due to fire suppression has likely lowered the root cohesion of some hollows. Quantification of this feedback between physiologic controls on root growth and slope hydrology has allowed us to create a curvature-based model of root cohesion that is a significant improvement on current models that assume a spatially averaged value

Reassessing changes in diurnal temperature range: Intercomparison and evaluation of existing global data set estimates

Changes in diurnal temperature range (DTR) over global land areas are compared from a broad range of independent data sets. All data sets agree that global-mean DTR has decreased significantly since 1950, with most of that decrease occurring over 1960–1980. The since-1979 trends are not significant, with inter-data set disagreement even over the sign of global changes. Inter-data set spread becomes greater regionally and in particular at the grid box level. Despite this, there is general agreement that DTR decreased in North America, Europe, and Australia since 1951, with this decrease being partially reversed over Australia and Europe since the early 1980s. There is substantive disagreement between data sets prior to the middle of the twentieth century, particularly over Europe, which precludes making any meaningful conclusions about DTR changes prior to 1950, either globally or regionally. Several variants that undertake a broad range of approaches to postprocessing steps of gridding and interpolation were analyzed for two of the data sets. These choices have a substantial influence in data sparse regions or periods. The potential of further insights is therefore inextricably linked with the efficacy of data rescue and digitization for maximum and minimum temperature series prior to 1950 everywhere and in data sparse regions throughout the period of record. Over North America, station selection and homogeneity assessment is the primary determinant. Over Europe, where the basic station data are similar, the postprocessing choices are dominant. We assess that globally averaged DTR has decreased since the middle twentieth century but that this decrease has not been linear

The global precipitation response to volcanic eruptions in the CMIP5 models

We examine the precipitation response to volcanic eruptions in the Coupled Model Intercomparison Project Phase 5 (CMIP5) historical simulations compared to three observational datasets, including one with ocean coverage. Global precipitation decreases significantly following eruptions in CMIP5 models, with the largest decrease in wet tropical regions. This also occurs in observational land data, and ocean data in the boreal cold season. Monsoon rainfall decreases following eruptions in both models and observations. In response to individual eruptions, the ITCZ shifts away from the hemisphere with the greater concentration of aerosols in CMIP5. Models undergo a longer-lasting ocean precipitation response than over land, but the response in the short satellite record is too noisy to confirm this. We detect the influence of volcanism on precipitation in all three datasets in the cold season, although the models underestimate the size of the response. In the warm season the volcanic influence is only marginally detectable

The Reliability of Global and Hemispheric Surface Temperature Records

The purpose of this review article is to discuss the development and associated estimation of uncertainties in the global and hemispheric surface temperature records. The review begins by detailing the groups that produce surface temperature datasets. After discussing the reasons for similarities and differences between the various products, the main issues that must be addressed when deriving accurate estimates, particularly for hemispheric and global averages, are then considered. These issues are discussed in the order of their importance for temperature records at these spatial scales: biases in SST data, particularly before the 1940s; the exposure of land-based thermometers before the development of louvred screens in the late 19th century; and urbanization effects in some regions in recent decades. The homogeneity of land-based records is also discussed; however, at these large scales it is relatively unimportant. The article concludes by illustrating hemispheric and global temperature records from the four groups that produce series in near-real time