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Contains fulltext : 304919.pdf (Publisher’s version ) (Open Access), BACKGROUND: The introduction of rituximab significantly improved the prognosis of diffuse large B-cell lymphoma (DLBCL), emphasizing the importance of evaluating the long-term consequences of exposure to radiotherapy, alkylating agents and anthracycline-containing (immuno)chemotherapy among DLBCL survivors. METHODS: Long-term risk of subsequent malignant neoplasms (SMNs) was examined in a multicenter cohort comprising 2373 5-year DLBCL survivors treated at ages 15-61 years in 1989-2012. Observed SMN numbers were compared with expected cancer incidence to estimate standardized incidence ratios (SIRs) and absolute excess risks (AERs/10 000 person-years). Treatment-specific risks were assessed using multivariable Cox regression. RESULTS: After a median follow-up of 13.8 years, 321 survivors developed one or more SMNs (SIR 1.5, 95% CI 1.3-1.8, AER 51.8). SIRs remained increased for at least 20 years after first-line treatment (SIR ≥20-year follow-up 1.5, 95% CI 1.0-2.2, AER 81.8) and were highest among patients ≤40 years at first DLBCL treatment (SIR 2.7, 95% CI 2.0-3.5). Lung (SIR 2.0, 95% CI 1.5-2.7, AER 13.4) and gastrointestinal cancers (SIR 1.5, 95% CI 1.2-2.0, AER 11.8) accounted for the largest excess risks. Treatment with >4500 mg/m(2) cyclophosphamide/>300 mg/m(2) doxorubicin versus ≤2250 mg/m(2)/≤150 mg/m(2), respectively, was associated with increased solid SMN risk (hazard ratio 1.5, 95% CI 1.0-2.2). Survivors who received rituximab had a lower risk of subdiaphragmatic solid SMNs (hazard ratio 0.5, 95% CI 0.3-1.0) compared with survivors who did not receive rituximab. CONCLUSION: Five-year DLBCL survivors have an increased risk of SMNs. Risks were higher for survivors ≤40 years at first treatment and survivors treated with >4500 mg/m(2) cyclophosphamide/>300 mg/m(2) doxorubicin, and may be lower for survivors treated in the rituximab era, emphasizing the need for studies with longer follow-up for rituximab-treated patients.

Item does not contain fulltext, BACKGROUND: Hodgkin lymphoma (HL) survivors treated with chest radiotherapy have an increased risk of breast cancer (BC). Prior HL treatment and associated cardiovascular disease (CVD) risk may limit BC treatment options. It is unknown how treatment adaptations affect BC and CVD outcomes. METHODS: The authors compared 195 BC patients treated with chest/axillary radiotherapy for HL (BC-HL) with 5988 age- and calendar year-matched patients with first primary BC (BC-1). Analyses included cumulative incidence functions and Cox regression models, accounting for tumor characteristics and BC treatment. RESULTS: Compared to BC-1 patients, BC-HL patients received anthracycline-containing chemotherapy (23.7% vs. 43.8%, p < .001) and breast-conserving surgery followed by radiotherapy (7.1% vs. 57.7%, p < .001) less often. BC treatment considerations were reported for 71% of BC-HL patients. BC-HL patients had a significantly higher risk of 15-year overall mortality than BC-1 patients (61% vs. 23%). Furthermore, risks of BC-specific mortality and nonfatal BC events were significantly increased among BC-HL patients, also when accounting for tumor and treatment characteristics (2.2- to 4.5-fold). BC-HL patients with a screen-detected BC had a significantly reduced (61%) BC-specific mortality. One-third of BC-HL patients had CVD at BC-diagnosis, compared to <0.1% of BC-1 patients. Fifteen-year CVD-specific mortality and CVD incidence were significantly higher in BC-HL patients than in BC-1 patients (15.2% vs. 0.4% and 40.4% vs. 6.8%, respectively), which was due to HL treatment rather than BC treatment. CONCLUSIONS: BC-HL patients experience a higher burden of CVD and worse BC outcomes than BC-1 patients. Clinicians should be aware of increased CVD risk when selecting BC treatment for HL survivors. LAY SUMMARY: Patients with breast cancer after Hodgkin lymphoma (BC-HL) may have limited options for BC treatment, due to earlier HL treatment and an associated increased risk of cardiov

Item does not contain fulltext, Little is known about the long-term health-related quality of life (HRQoL) and persistence of symptoms among patients with indolent non-Hodgkin lymphoma (iNHL). This large population-based longitudinal study therefore investigated the long-term HRQoL and persistence of symptoms and identified associated sociodemographic, clinical and psychological factors. Patients diagnosed between 1999 and 2014 and four or more months after diagnosis were invited to participate in a longitudinal survey. Sociodemographic and clinical data were obtained from the Netherlands Cancer Registry. The EORTC QLQ-C30 and CLL-16 were completed by 669 patients (74% response rate). Patients completed on average four questionnaires. Primary treatment was active surveillance (52%), systemic therapy (31%) or radiotherapy (13%). Respectively, 36% reported persistent fatigue, 33% persistent neuropathy and 25% persistent role-functioning impairment. This was 2-3 times higher than in the age- and sex-matched normative population. Up to 10 years after diagnosis, scores remained relatively stable without clinically relevant changes. Comorbidities, psychological distress, shorter time since diagnosis, systemic therapy, younger age, education level and having no partner were associated with worse outcomes (all ps < 0.05). Up to a third of patients with iNHL experience long-term persistent symptoms which do not improve over time. Early recognition of symptoms will help in providing tailored supportive care for those in need.

Item does not contain fulltext, BACKGROUND: Few studies have examined the impact of treatment-related morbidity on long-term, cause-specific mortality in Hodgkin lymphoma (HL) patients. METHODS: This multicenter cohort included 4919 HL patients, treated before age 51 years between 1965 and 2000, with a median follow-up of 20.2 years. Standardized mortality ratios, absolute excess mortality (AEM) per 10 000 person-years, and cause-specific cumulative mortality by stage and primary treatment, accounting for competing risks, were calculated. RESULTS: HL patients experienced a 5.1-fold (AEM = 123 excess deaths per 10 000 person-years) higher risk of death due to causes other than HL. This risk remained increased in 40-year survivors (standardized mortality ratio = 5.2, 95% confidence interval [CI] = 4.2 to 6.5, AEM = 619). At age 54 years, HL survivors experienced similar cumulative mortality (20.0%) from causes other than HL to 71-year-old individuals from the general population. Whereas HL mortality statistically significantly decreased over the calendar period (P < .001), solid tumor mortality did not change in the most recent treatment era. Patients treated in 1989-2000 had lower 25-year cardiovascular disease mortality than patients treated in 1965-1976 (4.3% vs 5.7%; subdistribution hazard ratio = 0.65, 95% CI = 0.46 to 0.93). Infectious disease mortality was not only increased after splenectomy but also after spleen irradiation (hazard ratio = 2.81, 95% CI = 1.55 to 5.07). For stage I-II, primary treatment with chemotherapy (CT) alone was associated with statistically significantly higher HL mortality (P < .001 for CT vs radiotherapy [RT]; P = .04 for CT vs RT+CT) but lower 30-year mortality from causes other than HL (15.8%, 95% CI = 9.7% to 23.3%) compared with RT alone (36.9%, 95% CI = 34.0% to 39.8%, P = .001) and RT and CT combined (29.8%, 95% CI = 26.8% to 32.9%, P = .02). CONCLUSIONS: Compared with the general population, HL survivors have a substantially reduced life expectancy. Optimal

Contains fulltext : 235296.pdf (Publisher’s version ) (Open Access), BACKGROUND: In premenopausal women, treatment with direct oral factor Xa inhibitors is associated with an increased risk of heavy menstrual bleeding (HMB) compared with vitamin K antagonists (VKA). Treatment with the direct oral thrombin inhibitor dabigatran appears to be associated with a reduced risk of HMB compared with VKA. These findings come from small observational studies or post hoc analyses of trials in which HMB was not a primary outcome. Use of tranexamic acid during the menstrual period may be effective in patients with HMB, but prospective data regarding efficacy and safety in patients on anticoagulant treatment are lacking. RATIONALE AND DESIGN: A direct comparison of a factor Xa inhibitor and a thrombin inhibitor with HMB as primary outcome, as well as an evaluation of the effects of adding tranexamic acid in women with anticoagulant-associated HMB is highly relevant for clinical practice. The MEDEA study is a randomized, open-label, pragmatic clinical trial to evaluate management strategies in premenopausal women with HMB associated with factor Xa inhibitor therapy. OUTCOMES: Women using factor Xa inhibitors with proven HMB, as assessed by a pictorial blood loss assessment chart (PBAC) score of >150, will be randomized to one of three study arms: (i) switch to dabigatran; (ii) continue factor Xa inhibitor with addition of tranexamic acid during the menstrual period; or (iii) continue factor Xa inhibitor without intervention. The primary outcome is the difference in PBAC score before and after randomization. Here, we present the rationale and highlight several unique features in the design of the study.

Treatment results of AML in elderly patients are unsatisfactory. We hypothesized that addition of tosedostat, an aminopeptidase inhibitor, to intensive chemotherapy may improve outcome in this population. After establishing a safe dose in a run-in phase of the study in 22 patients, 231 eligible patients with AML above 65 years of age (median 70, range 66–81) were randomly assigned in this open label randomized Phase II study to receive standard chemotherapy (3+7) with or without tosedostat at the selected daily dose of 120 mg (n = 116), days 1–21. In the second cycle, patients received cytarabine 1000 mg/m2 twice daily on days 1-6 with or without tosedostat. CR/CRi rates in the 2 arms were not significantly different (69% (95% C.I. 60–77%) vs 64% (55–73%), respectively). At 24 months, event-free survival (EFS) was 20% for the standard arm versus 12% for the tosedostat arm (Cox-p = 0.01) and overall survival (OS) 33% vs 18% respectively (p = 0.006). Infectious complications accounted for an increased early death rate in the tosedostat arm. Atrial fibrillation wa

Radboud University, 12 februari 2021, Promotor : Blijlevens, N.M.A. Co-promotores : Schols, S.E.M., Nijziel, M.R., Contains fulltext : 229980.pdf (publisher's version ) (Open Access)

Background: In premenopausal women, treatment with direct oral factor Xa inhibitors is associated with an increased risk of heavy menstrual bleeding (HMB) compared with vitamin K antagonists (VKA). Treatment with the direct oral thrombin inhibitor dabigatran appears to be associated with a reduced risk of HMB compared with VKA. These findings come from small observational studies or post hoc analyses of trials in which HMB was not a primary outcome. Use of tranexamic acid during the menstrual period may be effective in patients with HMB, but prospective data regarding efficacy and safety in patients on anticoagulant treatment are lacking. Rationale and Design: A direct comparison of a factor Xa inhibitor and a thrombin inhibitor with HMB as primary outcome, as well as an evaluation of the effects of adding tranexamic acid in women with anticoagulant-associated HMB is highly relevant for clinical practice. The MEDEA study is a randomized, open-label, pragmatic clinical trial to evaluate management strategies in premenopausal women with HMB associated with factor Xa inhibitor therapy. Outcomes: Women using factor Xa inhibitors with proven HMB, as assessed by a pictorial blood loss assessment chart (PBAC) score of >150, will be randomized to one of three study arms: (i) switch to dabigatran; (ii) continue factor Xa inhibitor with addition of tranexamic acid during the menstrual period; or (iii) continue factor Xa inhibitor without intervention. The primary outcome is the difference in PBAC score before and after randomization. Here, we present the rationale and highlight several unique features in the design of the study.

Contains fulltext : 201282.pdf (publisher's version ) (Closed access)

Contains fulltext : 183923.pdf (publisher's version ) (Open Access)

Contains fulltext : 193336.pdf (publisher's version ) (Open Access), Some comorbidities, such as hypertension, are associated with higher von Willebrand factor (VWF) levels in the general population. No studies have been conducted to assess this association in patients with von Willebrand disease (VWD). Therefore, we studied this association in patients with type 1 (n = 333) and type 2 (n = 203) VWD from the 'WiN" study. VWF antigen (VWF:Ag) was higher in type 1 VWD patients with hypertension [difference: 0.23 iu/ml, 95% confidence interval (CI): 0.11-0.35], diabetes mellitus (0.11 iu/ml, 95% CI: -0.02 to 0.23), cancer (0.14 iu/ml, 95% CI: 0.03-0.25) and thyroid dysfunction (0.14 iu/ml, 95% CI: 0.03-0.26) than in patients without these comorbidities (all corrected for age, sex and blood group). Similar results were observed for VWF collagen binding capacity (VWF:CB), VWF activity as measured by the VWF monoclonal antibody assay (VWF:Ab) and factor VIII (FVIII) coagulant activity (FVIII:C). In type 1 VWD, age was associated with higher VWF:Ag (0.03 iu/ml; 95% CI: 0.01-0.04), VWF:CB (0.02 iu/ml; 95% CI: 0.00-0.04), VWF:Ab (0.04 iu/ml; 95% CI: 0.02-0.06) and FVIII:C (0.03 iu/ml; 95% CI: 0.01-0.06) per decade increase. After adjustment for relevant comorbidities, these associations were no longer significant. Despite the higher VWF and FVIII levels, type 1 VWD patients with comorbidities had more bleeding episodes, particularly during surgery. There was no association between comorbidities and VWF/FVIII levels or bleeding phenotype in type 2 VWD patients. In conclusion, comorbidities are associated with higher VWF and FVIII levels in type 1 VWD and may explain the age-related increase of VWF and FVIII levels.

Some comorbidities, such as hypertension, are associated with higher von Willebrand factor (VWF) levels in the general population. No studies have been conducted to assess this association in patients with von Willebrand disease (VWD). Therefore, we studied this association in patients with type 1 (n = 333) and type 2 (n = 203) VWD from the ‘WiN” study. VWF antigen (VWF:Ag) was higher in type 1 VWD patients with hypertension [difference: 0·23 iu/ml, 95% confidence interval (CI): 0·11–0·35], diabetes mellitus (0·11 iu/ml, 95% CI: −0·02 to 0·23), cancer (0·14 iu/ml, 95% CI: 0·03–0·25) and thyroid dysfunction (0·14 iu/ml, 95% CI: 0·03–0·26) than in patients without these comorbidities (all corrected for age, sex and blood group). Similar results were observed for VWF collagen binding capacity (VWF:CB), VWF activity as measured by the VWF monoclonal antibody assay (VWF:Ab) and factor VIII (FVIII) coagulant activity (FVIII:C). In type 1 VWD, age was associated with higher VWF:Ag (0·03 iu/ml; 95% CI: 0·01–0·04), VWF:CB (0·02 iu/ml; 95% CI: 0·00–0·04), VWF:Ab (0·04 iu/ml; 95% CI: 0·02–0·06) and FVIII:C (0·03 iu/ml; 95% CI: 0·01–0·06) per decade increase. After adjustment for relevant comorbidities, these associations were no longer significant. Despite the higher VWF and FVIII levels, type 1 VWD patients with comorbidities had more bleeding episodes, particularly during surgery. There was no association between comorbidities and VWF/FVIII levels or bleeding phenotype in type 2 VWD patients. In conclusion, comorbidities are associated with higher VWF and FVIII levels in type 1 VWD and may explain the age-related increase of VWF and FVIII levels.

Contains fulltext : 171131.pdf (publisher's version ) (Open Access), BACKGROUND: The purpose of this study was to identify demographic, clinical, psychosocial, physical and environmental factors that are associated with participation in and adherence to a combined resistance and endurance exercise program among cancer survivors, shortly after completion of primary cancer treatment. Data from the randomized controlled Resistance and Endurance exercise After ChemoTherapy (REACT) study were used for this study. METHODS: The participants of the REACT study were randomly allocated to either a high intensity (HI) or low-to-moderate intensity (LMI) exercise program. Patients' participation rate was defined as the cancer survivors' decision to participate in the REACT study. Exercise adherence reflected participants' attendance to the scheduled exercise sessions and their compliance to the prescribed exercises. High session attendance rates were defined as attending at least 80 % of the sessions. High compliance rates were defined as performing at least of 90 % of the prescribed exercise across all sessions. Correlates of exercise adherence were studied separately for HI and LMI exercise. Demographic, clinical, and physical factors were assessed using self-reported questionnaires. Relevant clinical information was extracted from medical records. Multivariable logistic regression analyses were applied to identify correlates that were significantly associated with participation, high session attendance, high compliance with resistance and high compliance with endurance exercises. RESULTS: Participants were more likely to have higher education, be non-smokers, have lower psychological distress, higher outcome expectations, and perceive more exercise barriers than non-participants. In HI exercise, higher self-efficacy was significantly associated with high session attendance and high compliance with endurance exercises, and lower psychological distress was significantly associated with high compliance with resistance exercises. In LMI exercise

Contains fulltext : 172863.pdf (Publisher’s version ) (Open Access), TMPRSS6 variants that affect protein function result in impaired matriptase-2 function and consequently uninhibited hepcidin production, leading to iron refractory iron deficiency anemia (IRIDA). This disease is characterized by microcytic, hypochromic anemia and serum hepcidin values that are inappropriately high for body iron levels. Much is still unknown about its pathophysiology, genotype-phenotype correlation, and optimal clinical management. We describe 14 different TMPRSS6 variants, of which 9 are novel, in 21 phenotypically affected IRIDA patients from 20 families living in the Netherlands; 16 out of 21 patients were female. In 7 out of 21 cases DNA sequencing and multiplex ligation dependent probe amplification demonstrated only heterozygous TMPRSS6 variants. The age at presentation, disease severity, and response to iron supplementation were highly variable, even for patients and relatives with similar TMPRSS6 genotypes. Mono-allelic IRIDA patients had a milder phenotype with respect to hemoglobin and MCV and presented significantly later in life with anemia than bi-allelic patients. Transferrin saturation (TSAT)/hepcidin ratios were lower in IRIDA probands than in healthy relatives. Most patients required parenteral iron. Genotype alone was not predictive for the response to oral iron. We conclude that IRIDA is a genotypically and phenotypically heterogeneous disease. The high proportion of female patients and the discrepancy between phenotypes of probands and relatives with the same genotype, suggest a complex interplay between genetic and acquired factors in the pathogenesis of IRIDA. In the absence of inflammation, the TSAT/hepcidin ratio is a promising diagnostic tool, even after iron supplementation has been given. Am. J. Hematol. 91:E482-E490, 2016. (c) 2016 Wiley Periodicals, Inc.

Contains fulltext : 152550.pdf (publisher's version ) (Closed access)

Contains fulltext : 152645.pdf (publisher's version ) (Open Access), BACKGROUND: International evidence-based guidelines recommend physical exercise to form part of standard care for all cancer survivors. However, at present, the optimum exercise intensity is unclear. Therefore, we aimed to evaluate the effectiveness of a high intensity (HI) and low-to-moderate intensity (LMI) resistance and endurance exercise program compared with a wait list control (WLC) group on physical fitness and fatigue in a mixed group of cancer survivors who completed primary cancer treatment, including chemotherapy. METHODS: Overall, 277 cancer survivors were randomized to 12 weeks of HI exercise (n = 91), LMI exercise (n = 95), or WLC (n = 91). Both interventions were identical with respect to exercise type, duration and frequency, and only differed in intensity. Measurements were performed at baseline (4-6 weeks after primary treatment) and post-intervention. The primary outcomes were cardiorespiratory fitness (peakVO2), muscle strength (grip strength and 30-second chair-stand test), and self-reported fatigue (Multidimensional Fatigue Inventory; MFI). Secondary outcomes included health-related quality of life, physical activity, daily functioning, body composition, mood, and sleep disturbances. Multilevel linear regression analyses were performed to estimate intervention effects using an intention-to-treat principle. RESULTS: In the HI and LMI groups, 74 % and 70 % of the participants attended more than 80 % of the prescribed exercise sessions, respectively (P = 0.53). HI (beta = 2.2; 95 % CI, 1.2-3.1) and LMI (beta = 1.3; 95 % CI, 0.3-2.3) exercise showed significantly larger improvements in peakVO2 compared to WLC. Improvements in peakVO2 were larger for HI than LMI exercise (beta = 0.9; 95 % CI, -0.1 to 1.9), but the difference was not statistically significant (P = 0.08). No intervention effects were found for grip strength and the 30-second chair-stand test. HI and LMI exercise significantly reduced general and physical fatigue and reduced activity

Item does not contain fulltext, As survival of patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) increases and the number of patients who live long rises, health-related quality of life (HRQoL) becomes a relevant endpoint. Few studies investigated this, mainly as a secondary endpoint in randomized clinical trials where patients with early stage CLL/SLL, and elderly/frail patients were underrepresented. The aim of our study was to assess HRQoL in a population-based setting, including these previously underrepresented patients. Out of 175 patients diagnosed with CLL/SLL between 2004 and 2011, 136 (78 %) returned the HRQoL questionnaire. The outcomes were compared to an age- and sex-matched norm population. Detailed data on stage and treatment were extracted from a population-based hematological registry (PHAROS). Patients ever treated for CLL/SLL reported significantly poorer HRQoL than the norm population (p < 0.01 with large clinically important differences. Interestingly, no differences were observed between the norm population and patients under active surveillance. In contrast to our hypothesis, patients treated with chlorambucil reported the lowest HRQoL scores. Drastic, long-lasting negative effects of starting treatment on HRQoL cannot be excluded, whereas active surveillance does not seem to provoke worrying, anxiety, or depressive symptoms. Further elaborate research into the impact of starting therapy on HRQoL is needed, especially in patients that are underrepresented in most clinical trials, and thoroughly consider its results during revision of treatment guidelines.

1 oktober 2012, Item does not contain fulltext, We performed a nation-wide cross-sectional study to evaluate determinants of bleeding symptoms in a large unselected cohort of adults with von Willebrand disease (VWD). VWD patients were included (n=664), based on lowest historically measured VWF:Ag and VWF:Act levels 30 IU/dl. In type 3 patients 1 IU/dl FVIII:C decrease was associated with 0.6 point (95% CI 0.1-1.1) BS increase (p=0.021). In conclusion, in VWD patients the bleeding phenotype is strongly associated with type of VWD and VWF and FVIII levels.

01 maart 2012, Item does not contain fulltext, OBJECTIVE: Ischemic heart disease mortality is lower in hemophilia patients than in the general male population. As coagulation plays a role in the inflammatory pathways involved in atherogenesis, we investigated whether the clotting factor deficiency protects hemophilia patients from developing atherosclerosis. METHODS AND RESULTS: Coronary artery calcification, measured with multidetector-row computed tomography, was compared between 42 men, >/=59 years, with severe or moderate hemophilia A, and 613 nonhemophilic men from the Rotterdam Study, a prospective population-based study. None of the study subjects were HIV infected or had a history of cardiovascular disease. Coronary artery calcification was quantified by calculating the Agatston score and calcification mass. Data were analyzed using linear regression. Mean difference (beta) of the natural log-transformed Agatston score between men with and without hemophilia was 0.141 (95% CI -0.602 to 0.885, P=0.709). Results did not change after adjustment for age, body mass index, hypercholesterolemia, hypertension, and use of antidiabetic medication (beta=0.525, 95% CI -0.202 to 1.252, P=0.157). Comparable results were found for calcification mass. CONCLUSION: The extent of coronary artery atherosclerosis is comparable between elderly men with and without hemophilia. Results from this study underline the importance of screening and treating atherosclerosis risk factors in hemophilia patients.

We performed a nation-wide cross-sectional study to evaluate determinants of bleeding symptoms in a large unselected cohort of adults with von Willebrand disease (VWD). VWD patients were included (n=664), based on lowest historically measured VWF:Ag and VWF:Act levels ≤30 U/dl. Menorrhagia (85%), cutaneous bleeding (77%), bleeding from minor wounds (77%) and oral-cavity bleeding (62%) occurred most frequently. Higher age was associated with a higher bleeding score (BS), determined according to Tosetto, in females. A 10 year increase in age was associate

Item does not contain fulltext, Sweet syndrome, also known as acute febrile neutrophilic dermatosis, was diagnosed in two patients. Patient A, a 68-year-old man, had had chronic lymphatic leukaemia for four years, with a recent relapse. Patient B, a 58-year-old man, had been diagnosed with renal cell carcinoma four years earlier. Both patients presented with general discomfort, high fever, neutrophilic leukocytosis and diffuse, non-tender maculopapular exanthema, partly blanching on applied pressure, and vesicles spread over the body. Patient A had clinical signs of a septic shock. In both patients, histological examination confirmed clinical suspicion of Sweet syndrome and both had a good response on prednisone. In patient B, progression of renal cell carcinoma was found more than a half year later. It is important to recognise the varied clinical picture of the rare disorder that is Sweet syndrome because it can lead to severe clinical illness, especially in patients with an underlying malignancy.

Contains fulltext : 127627.pdf (publisher's version ) (Open Access)

Background: The aim of this study was to validate the Follicular Lymphoma International Prognostic Index (FLIPI) in a population-based cohort and to study the relevance of revision and extension of the FLIPI. Patients and methods: Data of 353 unselected patients, 1993-2002, in the Eindhoven Cancer Registry, were collected. Follow-up was completed up to 1 January 2006. Multiple imputations for missing covariates were used. Validity was assessed by comparing observed to predicted survival of the original model and of a revised model with other prognostic variables. Results: The original FLIPI stratified our cohort into three different risk groups based on stage, Hb, lactate dehydrogenase, nodal involvement and age. The discrimination between risk groups was not as good as in the original cohort. A model including age in three categories (≤60/ 61-70/>70 years) and presence of cardiovascular disease (CVD) (yes/ no) resulted in a better prognostic index. The 5-year overall survival rates were 79%, 59% and 28% in the low-, intermediate- and high-risk groups for the extended FLIPI compared with 81%, 66% and 47% for the original FLIPI, respectively. Conclusions: The performance of the FLIPIwas validated in a population-based setting, but could significantly be improved by a more refined coding of age and by including the presence of CVD.