Health-related quality of life after chemotherapy with or without rituximab in primary central nervous system lymphoma patients: results from a randomised phase III study.

BACKGROUND: The impact of rituximab on health-related quality of life (HRQoL) in primary central nervous system lymphoma patients is not well known. We determined the impact of rituximab added to standard high-dose methotrexate-based treatment on HRQoL in patients in a large randomised trial. PATIENTS AND METHODS: Patients from a large phase III trial (HOVON 105/ALLG NHL 24), randomly assigned to receive standard chemotherapy with or without rituximab and followed by 30 Gy whole brain radiotherapy (WBRT) in patients ≤60 years, completed the EORTC QLQ-C30 and QLQ-BN20 questionnaires before and during treatment, and up to 24 months of follow-up or progression. Differences between treatment arms over time in global health status, role functioning, social functioning, fatigue, and motor dysfunction were assessed. Differences ≥10 points were deemed clinically relevant. The effect of WBRT on HRQoL was analysed in irradiated patients. RESULTS: A total of 160/175 patients eligible for the HRQoL study completed at least one questionnaire and were included. Over time, scores improved statistically significantly and were clinically relevant in both arms. Between arms, there were no differences on any scale (range: -3.8 to +4.0). Scores on all scales were improved to a clinically relevant extent at 12 and 24 months compared with baseline in both arms, except for fatigue and motor dysfunction at 12 months (-7.4 and -8.8, respectively). In irradiated patients (n = 59), scores in all preselected scales, except motor dysfunction, remained stable up to 24 months compared with shortly after WBRT, overall mean difference ranging between 0.02 and 4.570. CONCLUSION: Compared with baseline, treatment resulted in improved HRQoL scores. The addition of rituximab to standard chemotherapy did not impact HRQoL over time. WBRT did not result in deterioration of HRQoL in the first 2 years.

Irrigation Scheduling Based on Wireless Sensors Output and Soil-Water Characteristic Curve in Two Soils.

Data-driven irrigation planning can optimize crop yield and reduce adverse impacts on surface and ground water quality. We evaluated an irrigation scheduling strategy based on soil matric potentials recorded by wireless Watermark (WM) sensors installed in sandy loam and clay loam soils and soil-water characteristic curve data. Five wireless WM nodes (IRROmesh) were installed at each location, where each node consisted of three WM sensors that were installed at 15, 30, and 60 cm depths in the crop rows. Soil moisture contents, at field capacity and permanent wilting points, were determined from soil-water characteristic curves and were approximately 23% and 11% for a sandy loam, and 35% and 17% for a clay loam, respectively. The field capacity level which occurs shortly after an irrigation event was considered the upper point of soil moisture content, and the lower point was the maximum soil water depletion level at 50% of plant available water capacity in the root zone, depending on crop type, root depth, growth stage and soil type. The lower thresholds of soil moisture content to trigger an irrigation event were 17% and 26% in the sandy loam and clay loam soils, respectively. The corresponding soil water potential readings from the WM sensors to initiate irrigation events were approximately 60 kPa and 105 kPa for sandy loam, and clay loam soils, respectively. Watermark sensors can be successfully used for irrigation scheduling by simply setting two levels of moisture content using soil-water characteristic curve data. Further, the wireless system can help farmers and irrigators monitor real-time moisture content in the soil root zone of their crops and determine irrigation scheduling remotely without time consuming, manual data logging and frequent visits to the field.

Treatment of sporadic Burkitt lymphoma in adults, a retrospective comparison of four treatment regimens.

Burkitt lymphoma is an aggressive B cell malignancy accounting for 1-2% of all adult lymphomas. Treatment with dose-intensive, multi-agent chemotherapy is effective but associated with considerable toxicity. In this observational study, we compared real-world efficacy, toxicity, and costs of four frequently employed treatment strategies for Burkitt lymphoma: the Lymphome Malins B (LMB), the Berlin-Frankfurt-Münster (BFM), the HOVON, and the CODOX-M/IVAC regimens. We collected data from 147 adult patients treated in eight referral centers. Following central pathology assessment, 105 of these cases were accepted as Burkitt lymphoma, resulting in the following treatment groups: LMB 36 patients, BFM 19 patients, HOVON 29 patients, and CODOX-M/IVAC 21 patients (median age 39 years, range 14-74; mean duration of follow-up 47 months). There was no significant difference between age, sex ratio, disease stage, or percentage HIV-positive patients between the treatment groups. Five-year progression-free survival (69%, p = 0.966) and 5-year overall survival (69%, p = 0.981) were comparable for all treatment groups. Treatment-related toxicity was also comparable with only hepatotoxicity seen more frequently in the CODOX/M-IVAC group (p = 0.004). Costs were determined by the number of rituximab gifts and the number of inpatients days. Overall, CODOX-M/IVAC had the most beneficial profile with regards to costs, treatment duration, and percentage of patients completing planned treatment. We conclude that the four treatment protocols for Burkitt lymphoma yield nearly identical results with regards to efficacy and safety but differ in treatment duration and costs. These differences may help guide future choice of treatment.

Psychological impact of lymphoma on adolescents and young adults: not a matter of black or white.

PURPOSE: The purpose of the study is to examine differences in perceived impact of cancer (IOC) between adolescents and young adults (AYAs; 18-35 years at cancer diagnosis), adults (36-64 years) and elderly (65-84 years) with a history of (non-)Hodgkin lymphoma. Furthermore, to investigate the association of socio-demographic, clinical and psychological characteristics with IOC; and the association between IOC and health-related quality of life (HRQoL) among AYAs only. METHODS: This study is part of a population-based PROFILES registry survey among lymphoma patients diagnosed between 1999 and 2009. Patients (n = 1.281) were invited to complete the IOCv1 and EORTC-QLQ-C30 questionnaires. Response rate was 67 % (n = 861). RESULTS: AYA lymphoma survivors scored higher on the positive IOC summary scale, compared to adult and elderly patients (p < 0.001), while no significant differences were observed for negative IOC. Among AYAs, females, survivors with a partner, and survivors with elevated psychological distress levels scored significantly higher on the negative IOC summary scale. The negative IOC summary scale was negatively associated with all EORTC QLQ-C30 functioning scales (ß ranging from -0.39 to -0.063; p < 0.05). The positive IOC summary scale was negatively associated with the EORTC QLQ-C30 subscale 'Emotional functioning' (ß = -0.24; p < 0.05). CONCLUSION: AYA, adult and elderly with a history of (non-)Hodgkin lymphoma experienced different types of IOC in terms of positive and negative aspects. IMPLICATIONS FOR CANCER SURVIVORS: Although AYAs experience a more positive IOC compared to older survivors, some AYAs experience more negative IOC and may require developmentally appropriate interventions to address their specific concerns.

Outcome and prognostic factors in patients with mantle-cell lymphoma relapsing after autologous stem-cell transplantation: a retrospective study of the European Group for Blood and Marrow Transplantation (EBMT).

BACKGROUND: Autologous stem-cell transplantation (autoSCT) is considered a standard treatment of non-frail patients with mantle cell lymphoma (MCL), but little is known about outcome of MCL patients relapsing after autoSCT. We therefore sought to analyse the outcome after autoSCT failure and the efficacy of a rescue stem-cell transplantation (SCT) in this setting. PATIENTS AND METHODS: Patients with MCL were eligible if they had relapsed after autoSCT performed between 2000 and 2009. A total of 1054 patients could be identified in the EBMT registry. By contacting the transplant centres, a full dataset could be retrieved for 360 patients. RESULTS: Median overall survival (OS) after relapse of the whole study group was 19 months. A long (>12 months) interval between autoSCT and relapse [P < 0.001, hazard ratio (HR) 0.62], primary refractory disease (P < 0.02, HR 1.92), prior high-dose ARA-C treatment (P = 0.04, HR 1.43), and the year of relapse (P = 0.02, HR 0.92) significantly influenced OS from relapse in multivariate analysis. Eighty patients (22%) received a rescue allogeneic SCT (alloSCT). Relapse incidence, non-relapse mortality, and OS 2 years after alloSCT was 33% [confidence interval (95% CI 21% to 45%)], 30% (95% CI 19% to 42%), and 46% (95% CI 33% to 59%), respectively. Remission duration after autoSCT was the only variable significantly affecting the outcome of salvage alloSCT. In contrast, rescue autoSCT was not associated with long-term disease control. However, individual patients survived long term even without salvage transplantation. CONCLUSIONS: MCL recurrence within 1 year after autoSCT has an extremely dismal outcome, while the prognosis of patients with longer remission durations after autoSCT is significantly better. AlloSCT may offer the possibility of durable survival when performed for patients with a remission duration of more than 12 months after first autoSCT, but the favourable effect of a salvage alloSCT in this setting needs further validation.

Reduced PTLD-related mortality in patients experiencing EBV infection following allo-SCT after the introduction of a protocol incorporating pre-emptive rituximab.

The mortality associated with post-transplant lymphoproliferative disorder (PTLD) induced by EBV infection can be reduced by monitoring EBV by polymerase-chain-reaction and rituximab given pre-emptively. We performed a retrospective analysis of the risk factors for the occurrence of EBV infection/disease and EBV-related mortality among 273 consecutive recipients of a T-cell-depleted allo-SCT during two periods: (a) before the implementation of a comprehensive protocol (2006-2008) and (b) afterwards (2009-2011). EBV infection was detected in 61 (22%) cases, and 28 cases were considered to have had EBV disease. Treatment with antithymocyte globulin was the most important risk factor (odds ratio (OR) 2.4; 95% confidence interval (CI) 1.3-4.2, P=0.001). After implementation of the protocol, in patients experiencing EBV infection, pre-emptive therapy was started more often and sooner (median 3 vs 6 days, P=0.002). Moreover, there were fewer cases of monomorphic PTLD (4/33 (12%) vs 11/28 (39%), P=0.01), and the EBV-related mortality was lower for patients experiencing EBV infection (2/33 (6%) vs 8/28 (29%), OR 0.2; 95% CI 0.05-0.9, P=0.03). The EBV protocol proved feasible and resulted in faster initiation of pre-emptive therapy, the diagnosis in an earlier stage of EBV disease, and decreased EBV-related mortality.

Centralised multidisciplinary re-evaluation of diagnostic procedures in patients with newly diagnosed Hodgkin lymphoma.

BACKGROUND: Hodgkin Lymphoma (HL) is highly curable when treated accurately. The challenge is to cure patients with the minimal risk of long-term complications. For that, optimal initial diagnostics are required to determine the optimal treatment plan. We offer non-academic hospitals in our Regional Comprehensive Cancer Centre network a centralised review of all diagnostic procedures from patients with newly diagnosed HL. We report our experience on concordances and discrepancies between local findings and central review results. PATIENTS AND METHODS: A haematologist and radiation oncologist at the Hodgkin Radboud University Nijmegen Medical Centre outpatient clinic examined all patients with newly diagnosed HL between February 2006 and May 2010. In a multidisciplinary lymphoma conference, diagnostic information is reviewed and treatment advice formulated. Discordant findings in pathology, staging and therapy were recorded as 'minor', no therapeutic consequences or 'major', adapted therapy advice. RESULTS: Altogether, 125 patients were included. Pathology review showed 86% concordance, with 4% major discordance, mainly nodular lymphocyte predominant sub-type. Revision of initial staging was concordant in 77%; however 15% major discordance of which most were upstaged. This resulted in 19% treatment adaption. CONCLUSION: Our findings highlight the discrepancies in interpretation of diagnostic tests. We advocate centralised review process for all newly diagnosed patients with HL.

Carbon dioxide flux as affected by tillage and irrigation in soil converted from perennial forages to annual crops.

Among greenhouse gases, carbon dioxide (CO(2)) is one of the most significant contributors to regional and global warming as well as climatic change. A field study was conducted to (i) determine the effect of soil characteristics resulting from changes in soil management practices on CO(2) flux from the soil surface to the atmosphere in transitional land from perennial forages to annual crops, and (ii) develop empirical relationships that predict CO(2) flux from soil temperature and soil water content. The CO(2) flux, soil temperature (T(s)), volumetric soil water content (theta(v)) were measured every 1-2 weeks in no-till (NT) and conventional till (CT) malt barley and undisturbed soil grass-alfalfa (UGA) systems in a Lihen sandy loam soil (sandy, mixed, frigid Entic Haplustoll) under irrigated and non-irrigated conditions in western North Dakota. Soil air-filled porosity (epsilon) was calculated from total soil porosity and theta(v) measurements. Significant differences in CO(2) fluxes between land management practices (irrigation and tillage) were observed on some measurement dates. Higher CO(2) fluxes were detected in CT plots than in NT and UGA treatments immediately after rainfall or irrigation. Soil CO(2) fluxes increased with increasing soil moisture (R(2)=0.15, P<0.01) while an exponential relationship was found between CO(2) emission and T(s) (R(2)=0.59). Using a stepwise regression analysis procedure, a significant multiple regression equation was developed between CO(2) flux and theta(v), T(s) (CO(2) flux = e(-3.477+0.123T(s)+6.381theta)(v); R(2)=0.68, P

Age-related changes in serum insulin-like growth factor-I, insulin-like growth factor-I binding protein-3 and articular cartilage structure in Thoroughbred horses.

REASONS FOR PERFORMING STUDY: Structural changes in articular cartilage associated with the ageing process require definition for investigators performing developmental and age-related studies, for which information is lacking. OBJECTIVES: To 1) determine the onset and end of puberty as defined by serum insulin like growth factor (IGF-I) and IGF-binding protein-3 (IGFBP-3) concentrations and 2) correlate articular-epiphyseal cartilage complex structural changes with the onset and end of puberty. METHODS: IGF-I and IGFBP-3 were measured in serum samples from normal female and male horses age 9-715 days to determine peak and steady-state values for horses transitioning through puberty. Osteochondral tissue sections were obtained from horses age 120-840 days (4-28 months) and examined histologically for cartilage canals and tidemark formation. RESULTS: In male and female horses, serum IGF-I/IGFBP-3 concentrations peaked at approximately 225 days, defining the onset of puberty. Cartilage canals were absent from articular cartilage just prior to this time point. IGF-I/IGFBP-3 concentrations declined to steady-state levels at approximately age 450 days, signalling exit from puberty and therefore the beginning of ageing. This time point correlated to initial formation of a tidemark in the osteochondral tissue sections. CONCLUSIONS: Horses may be considered pubescent at age 225-450 days, and post pubescent and ageing after age 450 days. POTENTIAL RELEVANCE: Defining the normal post natal to post pubescent concentrations for serum IGF-I and serum IGFBP-3 establishes subsets of animals for age-related studies and may be used to monitor horses for abnormally high IGF-I concentrations due to natural disease or subsequent to systemic growth hormone administration.

Improved diffusion methods for nitrogen and 15nitrogen analysis of Kjeldahl digests.

Simple methods are described that permit the use of either H3BO3 indicator solution or acidified filter disks to collect NH3 liberated by treatment of Kjeldahl digests with NaOH. These methods incorporate modifications to improve reliability, analytical capacity, and convenience. A semimicro digest was diluted to 25 mL with deionized water, and a 10 mL aliquot, containing up to 4 mg N (150 microg N for diffusions into acidified disks), was transferred to a shell vial, which was placed inside a 473 mL (1 pint) Mason jar containing 10 mL 10N NaOH. The NH3 liberated by overturning the vial was collected after 12 to 48 h at ambient temperature, or after 4 h at 45 to 50 degrees C on a hotplate, for quantitative and/or isotope-ratio analyses. With either H3BO3 indicator solution or acidified filter disks, recovery of diffused N was quantitative. Isotope-ratio analyses of diffused N from 15N-labeled chemical, plant, and soil samples were within 3% of analyses using steam distillation.

Use of nitrous oxide as a purge gas for automated nitrogen isotope analysis by the Rittenberg technique.

An apparatus that operates with an isotope-ratio mass spectrometer to automatically perform nitrogen isotope analyses by the Rittenberg technique was modified to permit the use of nitrous oxide (N(2)O) instead of Freon (CCl(2)F(2) or CHClF(2)) for the purging of air prior to hypobromite oxidation of ammonium-N to N(2) in a plastic microplate. Analytical performance was unaffected by the modifications. Up to 768 samples can be processed in a single loading, at a rate of 6 to 12 samples/h. Within the range of 0.2 to 20 atom % (15)N, isotope-ratio analyses of 50 to 200 mug of N using the automated Rittenberg apparatus (ARA) with a double-collector mass spectrometer were accurate to within 0.7%, as compared to manual Rittenberg analyses of 1 mg of N using the same mass spectrometer with a dual-inlet system. Automated analyses of 20mug of N were accurate to within 2%, and automated analyses of 10 mug of N were accurate to within 7%. The relative standard deviation for measurements at the natural abundance level (10 analyses, 20-200 mug of N) was < 0.04 %.