Survival after cancer-related venous thrombosis: the Scandinavian Thrombosis and Cancer Study.

Patients with cancer have an increased risk of developing venous thromboembolism (VTE), and this combination is reported to result in poorer survival compared with cancer alone. This study aimed to investigate the impact of VTE on the survival of patients with cancer in a general population. The Scandinavian Thrombosis and Cancer (STAC) cohort, a population-based cohort including 144 952 participants without previous VTE or cancer, was used. During follow-up, cancer and VTE incidences were registered. "Cancer-related VTE" was defined as VTE diagnosed in patients with overt or occult cancer. The survival of participants without cancer and/or VTE ("disease-free") was compared with the survival of participants with cancer and cancer-related VTE. Cox regression models with cancer and VTE as time-varying exposures were performed to calculate hazard ratios for death. Subanalyses were performed across cancer types and stages and VTE type (deep vein thrombosis or pulmonary embolism). During follow-up (mean, 11.7 years), 14 621 participants developed cancer, and 2444 developed VTE, of which 1241 were cancer-related. The mortality rates (per 100 person years) for disease-free participants, VTE only, cancer only, and cancer-related VTE were 0.63, 5.0, 9.2, and 45.3, respectively. Compared with patients with cancer only, the risk of death for patients with cancer-related VTE was increased 3.4-fold. Within all cancer types, the occurrence of VTE increased the mortality risk 2.8- to 14.7-fold. In a general population, patients with cancer with VTE had a 3.4-fold higher mortality risk than patients with cancer without VTE, independent of cancer type.

Association of smoking and cancer with the risk of venous thromboembolism: the Scandinavian Thrombosis and Cancer cohort.

Smoking is a well-established risk factor for cancer, and cancer patients have a high risk of venous thromboembolism (VTE). Conflicting results have been reported on the association between smoking and risk of VTE, and the effect of smoking on VTE-risk in subjects with cancer is scarcely studied. We aimed to investigate the association between smoking and VTE in subjects with and without cancer in a large population-based cohort. The Scandinavian Thrombosis and Cancer (STAC) cohort included 144,952 participants followed from 1993-1997 to 2008-2012. Information on smoking habits was derived from self-administered questionnaires. Active cancer was defined as the first two years following the date of cancer diagnosis. Former smokers (n = 35,890) and those with missing information on smoking status (n = 3680) at baseline were excluded. During a mean follow up of 11 years, 10,181 participants were diagnosed with cancer, and 1611 developed incident VTE, of which 214 were cancer-related. Smoking was associated with a 50% increased risk of VTE (HR 1.49, 95% CI 1.12-1.98) in cancer patients, whereas no association was found in cancer-free subjects (HR 1.07, 95% CI 0.96-1.20). In cancer patients, the risk of VTE among smokers remained unchanged after adjustment for cancer site and metastasis. Stratified analyses showed that smoking was a risk factor for VTE among those with smoking-related and advanced cancers. In conclusion, smoking was associated with increased VTE risk in subjects with active cancer, but not in those without cancer. Our findings imply a biological interaction between cancer and smoking on the risk of VTE.

Long-Term Incidence of Venous Thromboembolism in Cancer: The Scandinavian Thrombosis and Cancer Cohort.

The risk of venous thromboembolism (VTE) in patients who survive the first years after a cancer diagnosis after the acute effects of disease and treatment in comparison to a similar background population has been sparsely investigated. The aim of the study was to investigate if incidence rates (IRs) of VTE differed in patients who were alive at least 2 years after a cancer diagnosis without VTE compared with cancer-free references in a population-based cohort study. The study entry was 2 years after a first cancer diagnosis. For each cancer-exposed subject, five reference subjects were identified within the cohort. The IRs were calculated as number of VTEs per 1,000 person years (×10 -3 p-y) in total and in distinct cancer types and corresponding reference subjects. Incidence rate ratios (IRRs) were calculated by Poisson's regression. During a mean follow-up of 5.3 years, 110 VTEs occurred among the 7,288 cancer-exposed subjects and 321 VTEs occurred among the 36,297 identified reference subjects. The IR of VTE was higher for cancer-exposed subjects compared with reference subjects, IRs 3.7 × 10 -3 p-y, 95% CI: 3.1 to 4.5 and 1.9 × 10 -3 p-y, 95% CI: 1.7 to 2.2, respectively. IRs of VTE in most solid cancer types declined to almost the same level as in the reference subjects 2 years after cancer diagnosis, but remained higher in hematological cancers, IRR 4.0, 95% CI: 2.0 to 7.8.

Epidemiology of venous thromboembolism in hematological cancers: The Scandinavian Thrombosis and Cancer (STAC) cohort.

INTRODUCTION: Venous thromboembolism (VTE) is an important cause of morbidity and mortality in cancer patients, however the risk of VTE differs according to cancer type. Hematological cancers have varying phenotypes. Incidence rates (IR) of VTE in different hematological cancer types have not been investigated in a cancer-exposed subset of the general population. METHODS: In a population-based cohort, we estimated incidence rates of VTE among patients with six subtypes of hematological cancer and among age and sex matched reference subjects. RESULTS: During a mean follow-up of 4.8years, 30 objectively confirmed first-time symptomatic VTEs occurred among 838 subjects with hematological cancer. The IR of VTE was higher in all types of cancer except for indolent lymphoma but including chronic lymphocytic leukemia compared with reference subjects both during the first year after cancer diagnosis and 1-5years after diagnosis. IR of VTE for indolent lymphoma was not higher than controls. CONCLUSION: The IRs of VTE were increased in all types of hematological cancer (including chronic lymphocytic leukemia) compared with reference subjects except indolent lymphomas.

Association of Traditional Cardiovascular Risk Factors With Venous Thromboembolism: An Individual Participant Data Meta-Analysis of Prospective Studies.

BACKGROUND: Much controversy surrounds the association of traditional cardiovascular disease risk factors with venous thromboembolism (VTE). METHODS: We performed an individual level random-effect meta-analysis including 9 prospective studies with measured baseline cardiovascular disease risk factors and validated VTE events. Definitions were harmonized across studies. Traditional cardiovascular disease risk factors were modeled categorically and continuously using restricted cubic splines. Estimates were obtained for overall VTE, provoked VTE (ie, VTE occurring in the presence of 1 or more established VTE risk factors), and unprovoked VTE, pulmonary embolism, and deep-vein thrombosis. RESULTS: The studies included 244 865 participants with 4910 VTE events occurring during a mean follow-up of 4.7 to 19.7 years per study. Age, sex, and body mass index-adjusted hazard ratios for overall VTE were 0.98 (95% confidence interval [CI]: 0.89-1.07) for hypertension, 0.97 (95% CI: 0.88-1.08) for hyperlipidemia, 1.01 (95% CI: 0.89-1.15) for diabetes mellitus, and 1.19 (95% CI: 1.08-1.32) for current smoking. After full adjustment, these estimates were numerically similar. When modeled continuously, an inverse association was observed for systolic blood pressure (hazard ratio=0.79 [95% CI: 0.68-0.92] at systolic blood pressure 160 vs 110 mm Hg) but not for diastolic blood pressure or lipid measures with VTE. An important finding from VTE subtype analyses was that cigarette smoking was associated with provoked but not unprovoked VTE. Fully adjusted hazard ratios for the associations of current smoking with provoked and unprovoked VTE were 1.36 (95% CI: 1.22-1.52) and 1.08 (95% CI: 0.90-1.29), respectively. CONCLUSIONS: Except for the association between cigarette smoking and provoked VTE, which is potentially mediated through comorbid conditions such as cancer, the modifiable traditional cardiovascular disease risk factors are not associated with increased VTE risk. Higher systolic blood pressure showed an inverse association with VTE.

Existing data sources in clinical epidemiology: the Scandinavian Thrombosis and Cancer Cohort.

BACKGROUND: Although venous thromboembolism (VTE) is a known common complication in cancer patients, there is limited knowledge on patient-related and cancer-specific risk factors in the general population. The Scandinavian Thrombosis and Cancer (STAC) Cohort was established by merging individual data from three large Scandinavian cohorts (The Tromsø Study, the second Nord-Trøndelag Health Study, and the Danish Diet, Cancer and Health Study). Here, we present the profile of the STAC cohort and provide age-specific incidence rates of VTE and cancer. METHODS: The STAC cohort includes 144,952 subjects aged 19-101 years without previous VTE or cancer. Baseline information collected in 1993-1997 included physical examination, self-administered questionnaires, and blood samples. Validated VTE events and cancer diagnoses were registered up to 2007-2012. RESULTS: There were 2,444 VTE events (1.4 per 1,000 person-years [PY]) during follow-up, and the incidence increased exponentially from 0.3 per 1,000 PY in subjects aged 20-29 years to 6.4 per 1,000 PY in subjects aged 80+. Overall, 51% of the VTE events were provoked, and cancer was the most common provoking factor (19%), followed by immobilization and surgery (both 15%). In total, 19,757 subjects developed cancer during follow-up (9.8 per 1,000 PY), and the 5-year age-specific incidence rates of cancer were coherent with corresponding rates from the Norwegian Cancer Registry. CONCLUSION: The STAC cohort will provide a unique opportunity to explore the epidemiology and impact of genetic and environmental patient-related and cancer-specific risk factors for VTE in the general population.

Pain and bleeding associated with trephine biopsy.

The study objectives were to determine the intensity and duration of pain, factors that may influence pain experience during and after trephine biopsy, and to assess bleeding and infectious complications related to the procedure. Patients scheduled for trephine biopsy were recruited to the study. Local anesthesia was applied in all patients. Pain intensity was recorded twice daily by the patients using the numeric rating scale (NRS). Bleeding was graded into four grades. Median age of 184 patients was 63 yr. Maximum NRS level was measured at time of biopsy (T0); 167 (91%) patients experienced pain at T0. Median (Q1:Q3) NRS was 3 (1; 5). Median duration of pain was 36 h. Fourteen patients reported pain for more than 7 d. Significant inverse correlation was found between NRS at T0 and age. Pain duration at rest correlated with NRS at T0 and age, while pain duration in activity correlated with NRS at T0, age, and with body mass index (BMI). Mild and moderate bleeding at T0 occurred in 97 (54%) and 18 (10%) patients, respectively; no severe bleeding or infectious complications were registered. Secondary bleeding occurred in two patients; both required hospitalization. In conclusion, the study shows that despite the application of local anesthetic, more than 50% of the patients experienced pain of ≥ 3 points. Procedure-related bleeding is mild to moderate and managed by local pressure only.

Cladribine prolongs progression-free survival and time to second treatment compared to fludarabine and high-dose chlorambucil in chronic lymphocytic leukemia.

We conducted a randomized phase III trial to compare the efficacy and safety of two purine analogs, cladribine and fludarabine, with high-dose chlorambucil, in patients with previously untreated chronic lymphocytic leukemia (CLL). Between 1997 and 2004, 223 patients with CLL were randomly assigned to cladribine, fludarabine or chlorambucil, for six cycles of therapy with frequent health-related quality of life assessments. There was no statistical difference for the primary endpoint of overall response with cladribine (70%), fludarabine (67%) and chlorambucil (59%), or complete remission (12%, 7% and 8%), respectively. However, the median progression-free survival (25, 10, 9 months) and median time to second treatment (40, 22, 21 months) were superior with cladribine. There was no significant difference in overall survival (96, 82 and 91 months), nor in toxicity or HRQoL assessments. Monotherapy with cladribine gives superior PFS and longer response duration than fludarabine and chlorambucil as first-line treatment of CLL.

High-dose therapy with autologous stem cell support for lymphoma in Norway 1987-2008.

BACKGROUND: High-dose therapy with autologous stem cell support (HDT) has been a treatment option for lymphomas in Norway for 25 years. The purpose of the article was to describe the use of the therapy for lymphomas for the country as a whole and by health region, and to reveal the overall survival rate. METHOD: All lymphoma patients ≥ 18 years who received HDT in Norway in the period 1987-2008 are included. Patients, diagnostics and treatment are identified for each hospital. Data for the population base have been retrieved from Statistics Norway. RESULTS: Altogether 726 lymphoma patients received HDT in Norway in the period 1987-2008, with an annual average of 0.72 per 100,000 inhabitants. The annual number of treatments increased until 2004 and has since been stable. The average number of treatments per 100,000 inhabitants per year was 0.94 for Northern Norway Health Region, 0.80 for South-Eastern Norway Health Region, 0.58 for Central Norway Health Region and 0.55 for Western Norway Health Region. Early mortality (death within 100 days) was 6%. Ten-year overall survival was 55% (95% CI 51-59%), and Hodgkin's lymphoma had the best survival of the lymphoma groups (p = 0.01). INTERPRETATION: The annual number of HDT increased gradually until 2004. The use of the treatment varied according to the patients' place of residence at the time of diagnosis, and was most frequently used for patients belonging to Northern Norway Health Region. More than half of the lymphoma patients are alive ten years after the treatment.

High-dose therapy with autologous stem cell support for lymphoma--from experimental to standard treatment.

High-dose therapy with autologous stem cell support (HDT) has been a therapeutic option for lymphomas in Norway since as far back as 1987. By restoring bone marrow function through reinfusion of the patient's own stem cells, it is possible to administer cancer treatment in higher and otherwise lethal doses, and thereby achieve better treatment results. Originally stem cells were harvested from bone marrow and the high-dose therapy included total body irradiation, but since the mid 1990s stem cells have been harvested by apheresis and the high-dose therapy has consisted of chemotherapy alone (BEAM chemotherapy). In 1995 the treatment was regionalised and since then it has been performed in all health regions. The HDT procedure was introduced as an experimental treatment in clinical studies with international collaboration. The indications have changed over time, and this is now established treatment for a number of types of lymphoma.

Association of mild to moderate chronic kidney disease with venous thromboembolism: pooled analysis of five prospective general population cohorts.

BACKGROUND: Recent findings suggest that chronic kidney disease (CKD) may be associated with an increased risk of venous thromboembolism (VTE). Given the high prevalence of mild-to-moderate CKD in the general population, in depth analysis of this association is warranted. METHODS AND RESULTS: We pooled individual participant data from 5 community-based cohorts from Europe (second Nord-Trøndelag Health Study [HUNT2], Prevention of Renal and Vascular End-stage Disease [PREVEND], and the Tromsø study) and the United States (Atherosclerosis Risks in Communities [ARIC] and Cardiovascular Health Study [CHS]) to assess the association of estimated glomerular filtration rate (eGFR), albuminuria, and CKD with objectively verified VTE. To estimate adjusted hazard ratios for VTE, categorical and continuous spline models were fit by using Cox regression with shared-frailty or random-effect meta-analysis. A total of 1178 VTE events occurred over 599 453 person-years follow-up. Relative to eGFR 100 mL/min per 1.73 m(2), hazard ratios for VTE were 1.29 (95% confidence interval, 1.04-1.59) for eGFR 75, 1.31 (1.00-1.71) for eGFR 60, 1.82 (1.27-2.60) for eGFR 45, and 1.95 (1.26-3.01) for eGFR 30 mL/min per 1.73 m(2). In comparison with an albumin-to-creatinine ratio (ACR) of 5.0 mg/g, the hazard ratios for VTE were 1.34 (1.04-1.72) for ACR 30 mg/g, 1.60 (1.08-2.36) for ACR 300 mg/g, and 1.92 (1.19-3.09) for ACR 1000 mg/g. There was no interaction between clinical categories of eGFR and ACR (P=0.20). The adjusted hazard ratio for CKD, defined as eGFR <60 mL/min per 1.73 m(2) or albuminuria ≥30 mg/g, (versus no CKD) was 1.54 (95% confidence interval, 1.15-2.06). Associations were consistent in subgroups according to age, sex, and comorbidities, and for unprovoked versus provoked VTE, as well. CONCLUSIONS: Both eGFR and ACR are independently associated with increased risk of VTE in the general population, even across the normal eGFR and ACR ranges.

Arterial cardiovascular risk factors and venous thrombosis: results from a population-based, prospective study (the HUNT 2).

BACKGROUND: An explanation for the increased risk of myocardial infarction and stroke in patients with venous thrombosis is lacking. The objective of this study was to investigate whether risk factors for arterial cardiovascular disease also increase the risk of venous thrombosis. DESIGN AND METHODS: Cases who had a first venous thrombosis (n=515) and matched controls (n=1,505) were identified from a population-based, nested, case-cohort study (the HUNT 2 study) comprising 71% (n=66,140) of the adult residents of Nord-Trøndelag County in Norway. RESULTS: The age- and sex-adjusted odds ratio of venous thrombosis for subjects with concentrations of C-reactive protein in the highest quintile was 1.6 (95% confidence interval: 1.2-2.2) compared to subjects with C-reactive protein in the lowest quintile. This association was strongest in subjects who experienced venous thrombosis within a year after blood sampling with a three-fold increased risk of participants in the highest versus the lowest quintile. Having first degree relatives who had a myocardial infarction before the age of 60 years was positively associated with venous thrombosis compared to not having a positive family history [odds ratio 1.3 (95% confidence interval: 1.1-1.6)]. Subjects with blood pressure in the highest quintile had half the risk of developing venous thrombosis compared to subjects whose blood pressure was in the lowest quintile. There were no associations between the risk of venous thrombosis and total cholesterol, low density lipoprotein-cholesterol, high density lipoprotein-cholesterol, triglycerides, glucose or smoking. We confirmed the positive association between obesity and venous thrombosis. CONCLUSIONS: C-reactive protein and a family history of myocardial infarction were positively associated with subsequent venous thrombosis. Blood pressure was inversely correlated to venous thrombosis. These findings should be confirmed by further investigations.

Management of pregnant women with mechanical heart valve prosthesis: thromboprophylaxis with low molecular weight heparin.

INTRODUCTION: Pregnancy increases the risk of mechanical heart valve (MHV) thrombosis. Warfarin is protective, but implies risks to the fetus. Unfractionated heparin (UFH) is less effective but does not harm the fetus. In general, anticoagulation is more stable and predictable with low molecular weight heparin (LMWH) than with UFH. METHOD: Retrospective study of 12 pregnancies with MHV; 6 in aortic, 4 in mitral, and 2 in both positions, treated with therapeutic doses of subcutaneous LMWH twice daily throughout pregnancy. Doses were adjusted using anti-Xa monitoring. The frequency of thrombo-embolism with various anticoagulation regimes was calculated based on a literature review. RESULTS: Median LMWH dose was 15500 IU/24 h, range 10000-20000 IU/24 h; median dose 257 IU/kg/24 h. Median peak LMWH in blood plasma ranged 0.54-0.92 anti-Xa U/mL. Thromboembolism developed in two women with aortic MHV despite LMWH levels in target range. One had systemic embolic episodes; in the other woman valve thrombosis was successfully thrombolysed. Both had initially received subtherapeutic doses. Thrombo-embolism was not observed in ten pregnancies treated as recommended. The pregnancies resulted in thirteen healthy babies; eight delivered by Cesarean section. Bleeding occurred in two women after Cesarean section due to preeclampsia. CONCLUSION: Treatment with adjusted therapeutic doses of LMWH was successful in 10 of 12 pregnancies, and was not associated with fetal complications. Thromboembolism occurred in two pregnancies, possibly attributed to subtherapeutic doses of LMWH during the initial 3 weeks. Compared to UFH prophylaxis, therapeutic doses of LMWH appears to be more efficacious.

Hyperferritinemia is associated with insulin resistance and fatty liver in patients without iron overload.

OBJECTIVE: During the last 10 years we have experienced an increasing number of referrals due to hyperferritinemia. This is probably due to increased awareness of hereditary hemochromatosis, and the availability of a genetic test for this condition. Most of these referred patients were over-weight middle-aged men with elevated ferritin levels, but without the hemochromatosis-predisposing gene mutations. We evaluated the relationship between hyperferritinemia and the metabolic syndrome in 40 patients. METHODS: Forty consecutive patients referred for hyperferritinemia were investigated. The examination programme included medical history, clinical investigation and venous blood samples drawn after an overnight fast. This resulted in 34 patients with unexplained hyperferritinemia, which were further examined. Liver biopsy was successfully performed in 29 subjects. Liver iron stores were assessed morphologically, and by quantitative phlebotomy in 16 patients. RESULTS: The majority of the patients had markers of the metabolic syndrome, and 18 patients (52%) fulfilled the IDF-criteria for the metabolic syndrome. Mean body mass index was elevated (28.8+/-4.2), mean diastolic blood pressure was 88.5+/-10.5 mmHg, and mean fasting insulin C-peptide 1498+/-539 pmol/l. Liver histology showed steatosis and nuclear glycogen inclusions in most patients (19 out of 29). Only four patients had increased iron stores by histology, of which two could be explained by alcohol consumption. Fourteen of 16 patients normalized ferritin levels after phlebotomy of a cumulative blood amount corresponding to normal iron stores. Ferritin levels were significantly related to insulin C-peptide level (p<0.002) and age (p<0.002). CONCLUSION: The present results suggest that liver steatosis and insulin resistance but not increased iron load is frequently seen in patients referred for suspected hemochromatosis on the basis of hyperferritinemia. The ferritin level seems to be positively associated to insulin resistance.

[Bacteremia in hematological malignant disorders]. / Bakteriemi ved maligne blodsykdommer.

BACKGROUND: Bacteremia frequently complicates cytostatic treatment of hematological malignancies. Initial antibiotic treatment is chosen empirically before the results of cultures are available. Rational choices depend on updated knowledge of microbial resistance patterns. We have examined microorganisms in blood cultures over a 10-year period and compared them with the preceding 5-year period. MATERIAL AND METHODS: We analyzed isolates from blood cultures in patients with a hematological malignant disorder treated in the Hematology Unit, St. Olavs Hospital during the years 1995 - 2005. RESULTS: We found 373 isolates and 322 episodes of bacteremia in 225 patients. Most patients had acute leukemia or myeloma, with neutropenia after cytostatic treatment. The dominating pathogens were Escherichia coli (20 %), coagulase-negative staphylococci (13 %) and alpha-haemolytic streptococci (10 %). Enterococcus infections seem to occur more frequently and were associated with a high mortality. Gram-negative organisms constituted 48 % and gram-positive organisms 48 % of the isolates. About 3 / 4 of the patients had infections with penicillin-resistant bacteria. There was a low prevalence of organisms resistant to aminoglycoside. Acute leukemia patients with bacteremia had a 30-days all-cause mortality of 10.3 %. INTERPRETATION: We found small changes in the pattern of pathogens and antibiotic resistance over time. The rates of antibiotic resistance were favorable compared to other European countries. The mortality rate seems to be unchanged and acceptable. Penicillin G and aminoglycoside can still be considered as first-line treatment for suspected bacteremia in neutropenic patients in Norway.

[High-dose treatment of systemic AL-amyloidosis with autologous stem cell support]. / Høydosebehandling med autolog stamcellestøtte ved systemisk AL-amyloidose.

BACKGROUND: AL-amyloidosis is a serious disease with a short median survival without treatment. Treatment with high-dose melphalan with autologous stem cell support (HMAS) has a potential to increase survival, but is associated with toxicity and mortality. In this paper we report the Norwegian results retrospectively. MATERIAL AND METHODS: We used questionnaires and had personal contact with a local physician from each hospital with HMAS experience. Diagnosis and treatment were evaluated according to the guidelines at the time of treatment, and the results were compared to internationally published reports. RESULTS: Stem cell harvesting was attempted in 18 patients from 1997 to 2006. 15 of these received HMAS treatment. Treatment-related mortality was 20%, and 5 of 11 (45%) had an organ response. Median survival was not reached within the 55-month median observation time. The course of the disease was more complicated when known risk factors for HMAS treatment were present, such as reduced kidney function, advanced heart involvement, reduced performance status, and multiorgan disease. Three of 18 patients were not diagnosed according to relevant guidelines. In seven of 12 patients the response to treatment was not evaluated adequately with respect to haematology. INTERPRETATION: AL-amyloidosis is a difficult diagnosis and the condition is probably under-diagnosed in Norway. The results of HMAS treatment in Norway are comparable with those in published reports from centres abroad. The follow-up of patients should be improved.

Prospective study of homocysteine and MTHFR 677TT genotype and risk for venous thrombosis in a general population--results from the HUNT 2 study.

This case-cohort designed study prospectively investigated whether elevated homocysteine levels measured in blood samples drawn before the event and methylenetetrahydrofolate reductase (MTHFR) gene polymorphism (MTHFR C677T) were associated with subsequent first venous thrombosis (VT) in a general population. Between August 1995 and June 1997, blood was collected from 66 140 people in the second Norwegian Health Study of Nord-Trøndelag (HUNT2). During a seven-year follow-up, 505 VT cases were identified. 1458 age- and sex-matched controls were selected from the original cohort. Serum total homocysteine (tHcy) and MTHFR genotype were measured in stored samples that were drawn a median of 33 months before the events. The overall odds ratio (OR) was 1.50 [95% confidence interval (CI) 0.97-2.30] for homocysteine levels above versus below the 95th percentile. There was no graded association with VT over quintiles of homocysteine. In men the OR was 2.17 (95% CI 1.20-3.91) for levels above versus below the 95th percentile, but no association was found in women (OR 1.00). Stratification by age, predisposing risk factors or time to event did not change these results. The MTHFR 677TT genotype was not related to risk for VT. In conclusion, elevated homocysteine levels in the general population predicted subsequent first VT in men but not in women.

Adult acute lymphoblastic leukemia, Burkitt's lymphoma and lymphoblastic lymphoma in middle Norway 1985-2004.

We report a population-based investigation on adult acute precursor B lymphoblastic leukemia, Burkitt's lymphoma and T lymphoblastic lymphoma in a defined geographic area. The age-adjusted incidence rates for the three diagnostic groups were 0.47, 0.16 and 0.2 per 100,000 per year, respectively. Clinical characteristics and outcome following treatment are reported.