Physical mobility, physical activity, and obesity among elderly: findings from a large population-based Swedish survey.

OBJECTIVE: To examine how physical activity and physical mobility are related to obesity in the elderly. STUDY DESIGN: A cross-sectional study of 2558 men and women aged 65 years and older who participated in a population survey in 2012 was conducted in mid-Sweden with an overall response rate of 67%. METHODS: Obesity (body mass index ≥30 kg/m2) was based on self-reported weight and height, and physical activity and physical mobility on questionnaire data. Chi-squared test and multiple logistic regressions were used as statistical analyses. RESULTS: The overall prevalence of obesity was 19% in women and 15% in men and decreased after the age of 75 years. A strong association between both physical activity and obesity, and physical mobility and obesity was found. The odds for obesity were higher for impaired physical mobility (odds ratio [OR] 2.83, 95% confidence interval [CI] 2.14-3.75) than for physical inactivity (OR 1.63, 95% CI 1.28-2.08) when adjusted for gender, age, socio-economic status and fruit and vegetable intake. However, physical activity was associated with obesity only among elderly with physical mobility but not among those with impaired physical mobility. CONCLUSION: It is important to focus on making it easier for elderly with physical mobility to become or stay physically active, whereas elderly with impaired physical mobility have a higher prevalence of obesity irrespective of physical activity.

Treatment and outcome of 2904 CML patients from the EUTOS population-based registry.

The European Treatment and Outcome Study (EUTOS) population-based registry includes data of all adult patients newly diagnosed with Philadelphia chromosome-positive and/or BCR-ABL1+ chronic myeloid leukemia (CML) in 20 predefined countries and regions of Europe. Registration time ranged from 12 to 60 months between January 2008 and December 2013. Median age was 55 years and median observation time was 29 months. Eighty percent of patients were treated first line with imatinib, and 17% with a second-generation tyrosine kinase inhibitor, mostly according to European LeukemiaNet recommendations. After 12 months, complete cytogenetic remission (CCyR) and major molecular response (MMR) were achieved in 57% and 41% of patients, respectively. Patients with high EUTOS risk scores achieved CCyR and MMR significantly later than patients with low EUTOS risk. Probabilities of overall survival (OS) and progression-free survival for all patients at 12, 24 and 30 months was 97%, 94% and 92%, and 95%, 92% and 90%, respectively. The new EUTOS long-term survival score was validated: the OS of patients differed significantly between the three risk groups. The probability of dying in remission was 1% after 24 months. The current management of patients with tyrosine kinase inhibitors resulted in responses and outcomes in the range reported from clinical trials. These data from a large population-based, patient sample provide a solid benchmark for the evaluation of new treatment policies.

Prognosis of long-term survival considering disease-specific death in patients with chronic myeloid leukemia.

In patients with chronic myeloid leukemia (CML), first-line imatinib treatment leads to 8-year overall survival (OS) probabilities above 80%. Many patients die of reasons unrelated to CML. This work tackled the reassessment of prognosis under particular consideration of the probabilities of dying of CML. Analyses were based on 2290 patients with chronic phase CML treated with imatinib in six clinical trials. 'Death due to CML' was defined by death after disease progression. At 8 years, OS was 89%. Of 208 deceased patients, 44% died of CML. Higher age, more peripheral blasts, bigger spleen and low platelet counts were significantly associated with increased probabilities of dying of CML and determined a new long-term survival score with three prognostic groups. Compared with the low-risk group, the patients of the intermediate- and the high-risk group had significantly higher probabilities of dying of CML. The score was successfully validated in an independent sample of 1120 patients. In both samples, the new score differentiated probabilities of dying of CML better than the Sokal, Euro and the European Treatment and Outcome Study (EUTOS) score. The new score identified 61% low-risk patients with excellent long-term outcome and 12% high-risk patients. The new score supports the prospective assessment of long-term antileukemic efficacy and risk-adapted treatment.

The EUTOS population-based registry: incidence and clinical characteristics of 2904 CML patients in 20 European Countries.

This population-based registry was designed to provide robust and updated information on the characteristics and the epidemiology of chronic myeloid leukemia (CML). All cases of newly diagnosed Philadelphia positive, BCR-ABL1+ CML that occurred in a sample of 92.5 million adults living in 20 European countries, were registered over a median period of 39 months. 94.3% of the 2904 CML patients were diagnosed in chronic phase (CP). Median age was 56 years. 55.5% of patients had comorbidities, mainly cardiovascular (41.9%). High-risk patients were 24.7% by Sokal, 10.8% by EURO, and 11.8% by EUTOS risk scores. The raw incidence increased with age from 0.39/100,000/year in people 20-29 years old to 1.52 in those >70 years old, and showed a maximum of 1.39 in Italy and a minimum of 0.69 in Poland (all countries together: 0.99). The proportion of Sokal and Euro score high-risk patients seen in many countries indicates that trial patients were not a positive selection. Thus from a clinical point of view the results of most trials can be generalized to most countries. The incidences observed among European countries did not differ substantially. The estimated number of new CML cases per year in Europe is about 6370.

Impact of malignant stem cell burden on therapy outcome in newly diagnosed chronic myeloid leukemia patients.

Chronic myeloid leukemia (CML) stem cells appear resistant to tyrosine kinase inhibitors (TKIs) in vitro, but their impact and drug sensitivity in vivo has not been systematically assessed. We prospectively analyzed the proportion of Philadelphia chromosome-positive leukemic stem cells (LSCs, Ph+CD34+CD38-) and progenitor cells (LPCs, Ph+CD34+CD38+) from 46 newly diagnosed CML patients both at the diagnosis and during imatinib or dasatinib therapy (ClinicalTrials.gov NCT00852566). At diagnosis, the proportion of LSCs varied markedly (1-100%) between individual patients with a significantly lower median value as compared with LPCs (79% vs 96%, respectively, P=0.0001). The LSC burden correlated with leukocyte count, spleen size, hemoglobin and blast percentage. A low initial LSC percentage was associated with less therapy-related hematological toxicity and superior cytogenetic and molecular responses. After initiation of TKI therapy, the LPCs and LSCs rapidly decreased in both therapy groups, but at 3 months time point the median LPC level was significantly lower in dasatinib group compared with imatinib patients (0.05% vs 0.68%, P=0.032). These data detail for the first time the prognostic significance of the LSC burden at diagnosis and show that in contrast to in vitro data, TKI therapy rapidly eradicates the majority of LSCs in patients.

Sense of coherence and psychological well-being: improvement with age.

BACKGROUND: Psychological well-being is important for individuals, communities and health services throughout the world because of the costs associated with psychological ill-health and the loss of quality of life for those affected and their relatives. Following a salutogenic approach, there is a link between health-promoting resources, such as generalised resistance resources and a positive state of health. Generalised resistance resources have been proposed to relate to an individual's sense of coherence (SOC). The objectives of the present study were (i) to investigate SOC in relation to age and sex, (ii) to investigate psychological well-being in relation to age and sex, and (iii) to investigate the relationship between generalised resistance resources and psychological well-being. METHODS: A random sample of 43 598 respondents (54% female) aged 18-85 years participated in the present study via a postal survey questionnaire. SOC was measured by the SOC-13 and well-being by the General Health Questionnaire-12 questionnaire. RESULTS: Males had both stronger SOC and well-being compared to females. There was a relationship between SOC and age, with stronger SOC in the older age groups. There was a larger proportion of individuals who experienced well-being as a function of age. In addition, an increase in SOC was related to a decrease in psychological well-being, that is, a stronger SOC corresponded to higher well-being. CONCLUSION: Males showed a stronger SOC and more well-being than females. Moreover, SOC and well-being increased with age in both sexes. Our findings suggest that SOC may develop over a entire lifetime.

Clonal expansion of T/NK-cells during tyrosine kinase inhibitor dasatinib therapy.

Dasatinib, a broad-spectrum tyrosine kinase inhibitor (TKI), predominantly targets BCR-ABL and SRC oncoproteins and also inhibits off-target kinases, which may result in unexpected drug responses. We identified 22 patients with marked lymphoproliferation in blood while on dasatinib therapy. Clonality and immunophenotype were analyzed and related clinical information was collected. An abrupt lymphocytosis (peak count range 4-20 x 10(9)/l) with large granular lymphocyte (LGL) morphology was observed after a median of 3 months from the start of therapy and it persisted throughout the therapy. Fifteen patients had a cytotoxic T-cell and seven patients had an NK-cell phenotype. All T-cell expansions were clonal. Adverse effects, such as colitis and pleuritis, were common (18 of 22 patients) and were preceded by LGL lymphocytosis. Accumulation of identical cytotoxic T cells was also detected in pleural effusion and colon biopsy samples. Responses to dasatinib were good and included complete, unexpectedly long-lasting remissions in patients with advanced leukemia. In a phase II clinical study on 46 Philadelphia chromosome-positive acute lymphoblastic leukemia, patients with lymphocytosis had superior survival compared with patients without lymphocytosis. By inhibiting immunoregulatory kinases, dasatinib may induce a reversible state of aberrant immune reactivity associated with good clinical responses and a distinct adverse effect profile.

On the use of lonafarnib in myelodysplastic syndrome and chronic myelomonocytic leukemia.

Lonafarnib is an orally bio-available farnesyltransferase inhibitor that prevents farnesylation of specific target proteins including Ras. In a multicenter study, 67 patients with advanced myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia (CMML) were treated with a continuous oral dose of 200-300 mg of lonafarnib and were evaluated for hematologic, pathologic and pharmacodynamic response. The median age of patients was 70 years (range 44-86). There were 32 patients with MDS (RAEB-20 and RAEB-t-12) and 35 with CMML. Overall 16 (24%) of the patients responded with two patients achieving a complete remission and one a partial response. Responses were seen in 6/32 and 10/35 patients with MDS and CMML, respectively. Of the 19 patients who were platelet transfusion-dependent prior to treatment, 5 (26%) became transfusion-free for a median duration of 185 days. A decrease in the farnesylation of the HDJ-2 protein measured in patient-derived cells was observed in the majority of patients during treatment with lonafarnib, but no clear correlation between changes in farnesylation and clinical effect could be made. Gastrointestinal toxicity was significant with 19% of patients discontinuing therapy due to diarrhea, nausea and/or anorexia. Lonafarnib has demonstrable activity in patients with advanced MDS and CMML.

Lenograstim after autologous peripheral blood progenitor cell transplantation: results of a double-blind, randomized trial.

A phase III, randomized, double-blind, placebo-controlled, multi-center trial was conducted in order to compare the incidence of microbiologically defined infections occurring after high-dose chemotherapy (HDT) and ASCT in 98 patients given lenograstim (Granocyte) and 94 patients given placebo after transplantation. Hematopoietic recovery, the use of i.v. antibiotics, the numbers of red blood cell and platelet transfusions, the days spent in hospital, and the days on parenteral nutrition were also compared. The incidence of infections until neutrophil recovery was significantly less in patients who received lenograstim after HDT and ASCT as compared to patients who received placebo (66 of 98 vs 86 of 94 patients, P<0.001). Lenograstim also significantly reduced the use of i.v. antibiotics (P<0.001) and the median duration of i.v. antibiotic treatment (8 days vs 10 days, P=0.04), improved neutrophil recovery (absolute neutrophil count >0.5 x 10(9)/l: 11 days vs 15 days, P<0.001) and reduced the number of days spent in hospital (15 days vs 17 days, P<0.001). The administration of lenograstim after HDT and ASCT significantly reduces the incidence of microbiologically defined infections until neutrophil recovery. It also leads to less use of antibiotics and earlier discharge from hospital.

Granulocyte-macrophage colony-stimulating factor to increase efficacy of mitoxantrone, etoposide and cytarabine in previously untreated elderly patients with acute myeloid leukaemia: a Swedish multicentre randomized trial.

A total of 110 patients, aged 64 years or over, with de novo acute myeloid leukaemia (AML) and white blood cell counts <50 x 109/l were treated with 3 d of cytarabine 1 g/m2 twice daily, mitoxantrone 12 mg/m2 and etoposide 200 mg/m2, randomized with or without the addition of granulocyte-macrophage colony-stimulating factor (GM-CSF) 200 microg/m2. The primary aim was to evaluate the effect of GM-CSF on the remission rate. Secondary aims included comparison of duration of remission, survival and infectious complications and the impact of maintenance therapy with thioguanine. Complete remission (CR) was achieved by 64% of patients without GM-CSF, and by 65% of patients who received GM-CSF, the median remission duration was 13 vs. 6 months, the median overall survival (OS) was 14 vs. 9 months, the mean time to neutrophil recovery was 25 vs. 17 d (P = 0.03) and the number of positive blood cultures was 46 vs. 39 (P = 0.05) respectively. The impact of thioguanine remains unanswered since only 30 patients remained in CR after consolidation therapy. We conclude that induction therapy is feasible with acceptable toxicity in elderly patients with AML, albeit with a high relapse rate and short OS. GM-CSF prior to, and in combination with, induction treatment reduced the time to neutrophil recovery and the number of neutropenic septicaemia cases but did not improve the OS of AML in the elderly.

More efficient mobilisation of peripheral blood stem cells with HiDAC+AMSA+G-CSF than with mini-ICE+G-CSF in patients with AML.

We have compared the efficacy of two PBSC mobilisation regimens, mini-ICE+filgrastim (second consolidation) and HiDAC+AMSA+filgrastim (third consolidation), in two consecutive cohorts of patients with AML CR1 receiving treatment according to a joint protocol. Group A: 18 patients, aged 41 (21-65) years, were mobilised with mini-ICE (idarubicin 8 mg/m(2)+cytarabine 800 mg/m(2)+etoposide 150 mg/m(2) days 1-3) followed by filgrastim 300-480 microg once daily s.c. from day 11 after start of chemotherapy. Only four patients reached >5 CD34+ cells/microl blood (B-CD34+) and were able to undergo leukaphereses. Two out of 18 (11%) reached the defined target of >/=2.0 x 10(6) CD34+ cells/kg after 1-3 leukaphereses. Group B: 20 patients, aged 50 (29-67) years, received HiDAC+AMSA (cytarabine 3 g/m(2) b.i.d. days 1, 3, 5+amsacrine 150 mg/m(2) q.d. days 2, 4) followed by filgrastim at a similar dose starting on day 7. A total of 18 patients reached B-CD34+ >5/microl and underwent PBSC harvesting, starting on day 23 (14-29) and yielding 4.0 (0.9-21) x 10(6) CD34+ cells/kg. Of 20 patients, 17 (85%) reached the defined target of >/=2.0 x 10(6) CD34+ cells/kg after 1-3 leukaphereses. We conclude that HiDAC+AMSA+G-CSF - in contrast to mini-ICE+G-CSF - is an efficient regimen for mobilising PBSC in patients with AML CR1.

Long-term follow-up of patients >or=60 yr old with acute myeloid leukaemia treated with intensive chemotherapy.

It is still controversial how to treat elderly patients with acute myeloid leukaemia (AML), and results have been poor with most regimens. We report the long-term results of a randomised study performed by the Leukaemia Group of Middle Sweden during 1984-88 comparing two intensive chemotherapeutic drug combinations. Ninety patients >or=60-yr old with untreated AML were randomly allocated to treatment with daunorubicin, cytosine arabinoside (ara-C), and thioguanine (TAD) (43 patients) or a combination in which aclarubicin was substituted for daunorubicin (TAA) (47 patients). Forty-four patients (49%) entered complete remission (CR), 22/43 (51%) in the TAD group and 22/47 (47%) in the TAA group (ns). The CR rate in patients 70 yr 14/48 (29%) (P<0.0001). Early death within 30 d after treatment initiation was more often seen in patients >70 yr than in patients or=10 yr after inclusion of the last patient, 5/90 patients (one in the TAD group and four in the TAA group, respectively) were still alive, four in continuous complete remission and one in second complete remission. Thus, both treatment regimens appear to have similar efficacy, with a relatively high complete remission rate, and a reasonable survival as compared to other studies including some long-term survivors. However, early deaths are still numerous, particularly in patients above 70 yr of age, and the relapse rate is substantial.

Chronic myeloid leukemia and interferon-alpha: a study of complete cytogenetic responders.

Achieving a complete cytogenetic response (CCgR) is a major target in the treatment of chronic myeloid leukemia (CML) with interferon-alpha (IFN-alpha), but CCgRs are rare. The mean CCgR rate is 13%, in a range of 5% to 33%. A collaborative study of 9 European Union countries has led to the collection of data on 317 patients who were first seen between 1983 and 1997 and achieved CCgRs with IFN-alpha alone or in combination with hydroxyurea. The median time to first CCgR was 19 months (95% CI, 17-21; range, 3-84 months). At last contact, 212 patients were still alive and in continuous CCgR; 105 patients had lost CCgR, but 53% of them were still alive and in chronic phase. IFN-alpha treatment was discontinued permanently in 23 cases for response loss, in 36 cases for chronic toxicity (15 are still in unmaintained continuous CCgR), and in 8 cases because it was believed that treatment was no longer necessary (7 of these 8 patients are still in unmaintained continuous CCgR). The 10-year survival rate from first CCgR is 72% (95% CI, 62%-82%) and is related to the risk profile. High-risk patients lost CCgR more frequently and more rapidly and none survived more than 10 years. Low-risk patients survived much longer (10-year survival probability 89% for Sokal low risk and 81% for Euro low risk). These data point out that a substantial long-term survival in CCgRs is restricted mainly to low-risk and possibly intermediate-risk patients and occurs significantly less often in high-risk patients.

Prevalence of overweight and obesity in children and adolescents in a county in Sweden.

UNLABELLED: Overweight among young people in Sweden is increasing. The aim of the present study was to investigate the frequency of overweight and obesity based on body mass index (BMI) values among children and adolescents. Overweight was defined as a BMI value > or = 91st percentile and obesity as a BMI value > 98th percentile on an international reference BMI curve. The study population included boys and girls from four age groups: 9, 12, 15 and 18 y. The data consisted of self-reported measures of height and weight that were obtained from questionnaires used in a cross-sectional study in December 1997. A validation study was performed using a part of the study population. A total of 7011 (81.7%) participants completed the questionnaire. The correlation between self-reported estimations and objective measures of height and weight was high in the oldest age groups (0.88-0.98), but lower in the 9-y-old age groups (0.37-0.72). These self-reported estimations in the 9-y-olds were excluded from further analysis. It was found that 12.3%, 11.6% and 11.4% of the boys in the 12-, 15- and 18-y-old age groups and 6.8%, 5.5% and 4.8% of the girls in the same age groups were overweight and 7.9%, 8.9% and 7.3% of the boys and 5.1%, 4.2% and 3.9% of the girls were obese. CONCLUSION: The prevalence of overweight and obesity was found to be high in the study population and is a serious public health problem. The prevalence of obesity was significantly higher (p < 0.05) in 15-y-old boys living in rural areas than in city and town dwellers of the same age.

Manifold-assisted reverse transcription-PCR with real-time detection for measurement of the BCR-ABL fusion transcript in chronic myeloid leukemia patients.

BACKGROUND: BCR-ABL fusion mRNA expression in bone marrow or peripheral blood can be used as a measure of minimal residual disease in patients with chronic myeloid leukemia (CML). METHODS: We used an oligo(dT)-coated manifold support to capture the mRNA directly from the cell lysate. After reverse transcription, the cDNA was eluted from the manifold support, and BCR-ABL and GAPDH mRNAs were quantified in real time using the TaqMan fluorogenic detection system. RESULTS: The detection limit of the method was one positive K562 cell among 10(5) negative cells. GAPDH was chosen as a reference gene based on the low variation between samples from different stages of the disease and the low signal in the absence of reverse transcription. The day-to-day variation of the method (CV) was 32%. In 43 blood samples from 13 CML patients, mRNA quantification agreed well with cytogenetic data. CONCLUSIONS: The proposed procedure constitutes a reproducible and sensitive BCR-ABL mRNA quantification method and is suitable to monitor minimal residual disease in CML patients.

Roquinimex (Linomide) vs placebo in AML after autologous bone marrow transplantation.

Roquinimex, Linomide, a quinoline derivative with pleiotropic immunomodulatory activity, has previously been shown to enhance natural killer (NK) cell number and activity after ABMT in patients with AML. In this study 278 AML patients in remission were randomized to receive Roquinimex 0.2 mg/kg body weight or placebo twice weekly for 2 years following ABMT. Out of 139 patients in each group, 109 Roquinimex patients and 108 placebo patients were in their first CR. Median age at inclusion was 41 years for Roquinimex patients and 39 years for placebo patients. Twelve patients in each group had their marrow purged prior to reinfusion. Relapse and death were study endpoints. Surviving patients were followed for 2.6 to 6. 9 years. The total number of relapses was 60 in the Roquinimex group and 63 in the placebo group (not significant). Leukemia-free and overall survivals were similar in the two groups. Recovery of platelet counts was significantly delayed in the Roquinimex group as compared to placebo. No other significant differences regarding toxicity parameters were recorded. In conclusion, previous findings on NK cells could not be confirmed and the study showed no benefit for Roquinimex over placebo regarding relapse or survival following ABMT for AML in remission.