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1.
  • Chen, X., et al. (författare)
  • A genome-wide association study of IgM antibody against phosphorylcholine: shared genetics and phenotypic relationship to chronic lymphocytic leukemia
  • 2018
  • Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 27:10, s. 1809-1818
  • Tidskriftsartikel (refereegranskat)abstract
    • Phosphorylcholine (PC) is an epitope on oxidized low-density lipoprotein (oxLDL), apoptotic cells and several pathogens like Streptococcus pneumoniae. Immunoglobulin M against PC (IgM anti-PC) has the ability to inhibit uptake of oxLDL by macrophages and increase clearance of apoptotic cells. From our genome-wide association studies (GWASs) in four European-ancestry cohorts, six single nucleotide polymorphisms (SNPs) in 11q24.1 were discovered (in 3002 individuals) and replicated (in 646 individuals) to be associated with serum level of IgM anti-PC (the leading SNP rs35923643-G, combined beta = 0.19, 95% confidence interval 0.13-0.24, P = 4.3 x 10-11). The haplotype tagged by rs35923643-G (or its proxy SNP rs735665-A) is also known as the top risk allele for chronic lymphocytic leukemia (CLL), and a main increasing allele for general IgM. By using summary GWAS results of IgM anti-PC and CLL in the polygenic risk score (PRS) analysis, PRS on the basis of IgM anti-PC risk alleles positively associated with CLL risk (explained 0.6% of CLL variance, P = 1.2 x 10-15). Functional prediction suggested that rs35923643-G might impede the binding of Runt-related transcription factor 3, a tumor suppressor playing a central role in the immune regulation of cancers. Contrary to the expectations from the shared genetics between IgM anti-PC and CLL, an inverse relationship at the phenotypic level was found in a nested case-control study (30 CLL cases with 90 age- and sex-matched controls), potentially reflecting reverse causation. The suggested function of the top variant as well as the phenotypic association between IgM anti-PC and CLL risk needs replication and motivates further studies.
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  • Baecklund, Eva, 1956-, et al. (författare)
  • Anti-cyclic citrullinated peptide antibodies, other common autoantibodies, and smoking as risk factors for lymphoma in patients with rheumatoid arthritis
  • 2018
  • Ingår i: Scandinavian Journal of Rheumatology. - : Informa UK Limited. - 0300-9742 .- 1502-7732. ; 47:4, s. 270-275
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: Patients with rheumatoid arthritis (RA) are at increased risk of lymphoma. There is no biomarker to indicate future lymphoma risk in RA and it is not known whether factors associated with an increased risk of RA also confer an increased risk of lymphoma. We investigated whether anti-cyclic citrullinated peptide (CCP) antibodies, other autoantibodies, and smoking, are associated with lymphoma development in RA.METHOD: subclasses of anti-CCP antibodies and for 15 antinuclear antibody (ANA)-associated specific autoantibodies. Relative risks were estimated as crude and adjusted odds ratios (adjOR) with 95% confidence intervals (CIs) using logistic regression.RESULTS: We found no association between anti-CCP IgG ≥ 25 units/mL (adjOR 1.4, 95% CI 0.7-2.7), anti-CCP IgG ≥ 500 units/mL (adjOR 1.4, 95% CI 0.7-3.0), anti-CCP Ig of other isotypes, other autoantibodies (adjOR any vs none 0.6, 95% CI 0.3-1.2), or cigarette smoking (adjOR ever vs never 1.1, 95% CI 0.5-2.2) and lymphoma risk among patients with RA.CONCLUSION: In this study, neither anti-CCP antibodies (IgG, IgG1–4, IgM, or IgA), nor other common autoantibodies, nor smoking predicted lymphoma risk in RA
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  • Baliakas, Panagiotis, et al. (författare)
  • Recurrent mutations refine prognosis in chronic lymphocytic leukemia
  • 2015
  • Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 0887-6924 .- 1476-5551. ; 29, s. 329-336
  • Tidskriftsartikel (refereegranskat)abstract
    • Through the European Research Initiative on chronic lymphocytic leukemia (CLL) (ERIC), we screened 3490 patients with CLL for mutations within the NOTCH1 (n=3334), SF3B1 (n=2322), TP53 (n=2309), MYD88 (n=1080) and BIRC3 (n=919) genes, mainly at diagnosis (75%) and before treatment (>90%). BIRC3 mutations (2.5%) were associated with unmutated IGHV genes (U-CLL), del(11q) and trisomy 12, whereas MYD88 mutations (2.2%) were exclusively found among M-CLL. NOTCH1, SF3B1 and TP53 exhibited variable frequencies and were mostly enriched within clinically aggressive cases. Interestingly, as the timespan between diagnosis and mutational screening increased, so too did the incidence of SF3B1 mutations; no such increase was observed for NOTCH1 mutations. Regarding the clinical impact, NOTCH1 mutations, SF3B1 mutations and TP53 aberrations (deletion/mutation, TP53ab) correlated with shorter time-to-first-treatment (P<0.0001) in 889 treatment-naive Binet stage A cases. In multivariate analysis (n=774), SF3B1 mutations and TP53ab along with del(11q) and U-CLL, but not NOTCH1 mutations, retained independent significance. Importantly, TP53ab and SF3B1 mutations had an adverse impact even in U-CLL. In conclusion, we support the clinical relevance of novel recurrent mutations in CLL, highlighting the adverse impact of SF3B1 and TP53 mutations, even independent of IGHV mutational status, thus underscoring the need for urgent standardization/harmonization of the detection methods.
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  • Cahill, Nicola, et al. (författare)
  • 450K-array analysis of chronic lymphocytic leukemia cells reveals global DNA methylation to be relatively stable over time and similar in resting and proliferative compartments
  • 2013
  • Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 1476-5551 .- 0887-6924. ; 27:1, s. 150-158
  • Tidskriftsartikel (refereegranskat)abstract
    • In chronic lymphocytic leukemia (CLL), the microenvironment influences gene expression patterns; however, knowledge is limited regarding the extent to which methylation changes with time and exposure to specific microenvironments. Using high-resolution 450K arrays, we provide the most comprehensive DNA methylation study of CLL to date, analyzing paired diagnostic/follow-up samples from IGHV-mutated/untreated and IGHV-unmutated/treated patients (n = 36) and patient-matched peripheral blood and lymph node samples (n = 20). On an unprecedented scale, we revealed 2239 differentially methylated CpG sites between IGHV-mutated and unmutated patients, with the majority of sites positioned outside annotated CpG islands. Intriguingly, CLL prognostic genes (for example, CLLU1, LPL, ZAP70 and NOTCH1), epigenetic regulator (for example, HDAC9, HDAC4 and DNMT3B), B-cell signaling (for example, IBTK) and numerous TGF-beta and NF-kappa B/TNF pathway genes were alternatively methylated between subgroups. Contrary, DNA methylation over time was deemed rather stable with few recurrent changes noted within subgroups. Although a larger number of non-recurrent changes were identified among IGHV-unmutated relative to mutated cases over time, these equated to a low global change. Similarly, few changes were identified between compartment cases. Altogether, we reveal CLL subgroups to display unique methylation profiles and unveil methylation as relatively stable over time and similar within different CLL compartments, implying aberrant methylation as an early leukemogenic event. Leukemia (2013) 27, 150-158; doi:10.1038/leu.2012.245
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7.
  • Chen, L., et al. (författare)
  • Risk of disability pension in patients following rectal cancer treatment and surgery
  • 2015
  • Ingår i: British Journal of Surgery. - : Oxford University Press (OUP). - 0007-1323 .- 1365-2168. ; 102:11, s. 1426-1432
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundAspects of survivorship, such as long-term ability to work, are increasingly relevant owing to the improved survival of patients with rectal cancer. The aim of this study was to assess risk and determinants of disability pension (DP) in this patient group. MethodsUsing Swedish national clinical and population-based registers, patients with stage I-III rectal cancer aged 18-61years in 1995-2009 were identified at diagnosis and matched with population comparators. Prospectively registered records of DP during follow-up were retrieved up to 2013. Non-proportional and proportional hazards models were used to estimate the incidence rate ratio (IRR) for DP annually and overall. Potential variations in risk by demographic and clinical factors were calculated, with relapse as a time-varying exposure. ResultsA total of 2815 patients were identified and compared with 13465 population comparators. During a median follow-up of 60 (range 0-10) years, 233 per cent of the relapse-free patients and 103 per cent of the population comparators received DP (IRR 240, 95 per cent c.i. 217 to 265). An increased annual risk of DP was evident almost every year until the tenth year of follow-up. Abdominoperineal resection was associated with an increased DP risk compared with anterior resection (IRR 144, 119 to 175). Surgical complications (IRR 133, 110 to 162) and reoperation (IRR 142, 109 to 184), but not radiotherapy or chemotherapy, were associated with risk of DP. ConclusionRelapse-free patients with rectal cancer of working age are at risk of disability pension. Higher than expected
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  • Cozen, W., et al. (författare)
  • A meta-analysis of Hodgkin lymphoma reveals 19p13.3 TCF3 as a novel susceptibility locus
  • 2014
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 5, s. 3856-
  • Tidskriftsartikel (refereegranskat)abstract
    • Recent genome-wide association studies (GWAS) of Hodgkin lymphoma (HL) have identified associations with genetic variation at both HLA and non-HLA loci; however, much of heritable HL susceptibility remains unexplained. Here we perform a meta-analysis of three HL GWAS totaling 1,816 cases and 7,877 controls followed by replication in an independent set of 1,281 cases and 3,218 controls to find novel risk loci. We identify a novel variant at 19p13.3 associated with HL (rs1860661; odds ratio (OR) = 0.81, 95% confidence interval (95% CI) = 0.76-0.86, P-combined 3.5 x 10(-10)), located in intron 2 of TCF3 (also known as E2A), a regulator of B-and T-cell lineage commitment known to be involved in HL pathogenesis. This meta-analysis also notes associations between previously published loci at 2p16, 5q31, 6p31, 8q24 and 10p14 and HL subtypes. We conclude that our data suggest a link between the 19p13.3 locus, including TCF3, and HL risk.
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  • Ekberg, S., et al. (författare)
  • Long-term survival and loss in expectancy of life in a population-based cohort of 7114 patients with diffuse large B-cell lymphoma
  • 2018
  • Ingår i: American Journal of Hematology. - : Wiley. - 0361-8609 .- 1096-8652. ; 93:8, s. 1020-1028
  • Tidskriftsartikel (refereegranskat)abstract
    • Survival has improved among patients with diffuse large B-cell lymphoma (DLBCL) with the addition of anti-CD20 antibody therapy. We aimed to quantify trends and remaining loss in expectation of life (LEL) due to DLBCL at a national population-based level. Patients diagnosed with DLBCL 2000-2013 (N=7114) were identified through the Swedish Lymphoma Registry and classified according to the age-adjusted International Prognostic Index (aaIPI). The novel measure LEL is the difference between remaining life years among patients and the general population and was predicted using flexible parametric models from diagnosis and among 2-year survivors, by age and sex. Median age at DLBCL-diagnosis was 70 (18-105) years and 54.8% presented with stage III-IV disease. On average, LEL due to DLBCL decreased from 8.0 (95% CI: 7.7-8.3) to 4.6 (95% CI: 4.5-4.6) years over the study period. By risk group, LEL was most reduced among patients with aaIPI >= 2 aged 50-60 years. However, these patients were still estimated to lose >8 years in 2013 (eg, LELmales50years 8.6 years (95% CI: 5.0-12.3)). Among 2-year survivors, LEL was reduced from 6.1 years (95% CI: 5.6-6.5) (aaIPI >= 2) and 3.8 years (95% CI: 3.6-4.1) (aaIPI<2) to 1.1 (95% CI: 1.1-1.2) and 1.0 year (95% CI: 0.8-1.1), respectively. The reduction was observed across all ages. Results for females were similar. By using LEL we illustrate the improvement of DLBCL survival over time. Despite adequate immunochemotherapy, substantial LEL among patients with IPI >= 2 points to remaining unmet medical needs. We speculate that observed reduced losses among 2-year survivors indicate a reduction of late relapses.
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  • Ekberg, S., et al. (författare)
  • Myocardial infarction in diffuse large B-cell lymphoma patients - a population-based matched cohort study
  • 2021
  • Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 290:5, s. 1048-1060
  • Tidskriftsartikel (refereegranskat)abstract
    • Background The outcome for diffuse large B-cell lymphoma (DLBCL) patients has improved with the immunochemotherapy combination R-CHOP. An increased rate of heart failure is well documented following this treatment, whereas incidence and outcome of other cardiac complications, for example myocardial infarction, are less well known. Method We identified 3548 curatively treated DLBCL patients in Sweden diagnosed between 2007 and 2014, and 35474 matched lymphoma-free general population comparators. The incidence, characteristics and outcome of acute myocardial infarctions (AMIs) were assessed using population-based registers up to 11 years after diagnosis. The rate of AMI was estimated using flexible parametric models. Results Overall, a 33% excess rate of AMI was observed among DLBCL patients compared with the general population (HR: 1.33, 95% CI: 1.14-1.55). The excess rate was highest during the first year after diagnosis and diminished after 2 years. High age, male sex and comorbidity were the strongest risk factors for AMI. Older patients (>70 years) with mild comorbidities (i.e. hypertension or diabetes) had a 61% higher AMI rate than comparators (HR: 1.61, 95% CI: 1.10-2.35), whereas the corresponding excess rate was 28% for patients with severe comorbidities (HR: 1.28, 95% CI: 1.01-1.64). Among younger patients (<= 70), a short-term excess rate of AMI was limited to those with severe comorbidities. There was no difference in AMI characteristics, pharmacological treatment or 30-day survival among patients and comparators. Conclusion DLBCL patients have an increased risk of AMI, especially during the first 2 years, which calls for improved cardiac monitoring guided by age and comorbidities. Importantly, DLBCL was not associated with differential AMI management or survival.
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  • Fernberg, P., et al. (författare)
  • Time Trends in Risk and Risk Determinants of Non-Hodgkin Lymphoma in Solid Organ Transplant Recipients
  • 2011
  • Ingår i: American Journal of Transplantation. - : Elsevier BV. - 1600-6135 .- 1600-6143. ; 11:11, s. 2472-2482
  • Tidskriftsartikel (refereegranskat)abstract
    • Organ transplantation increases risk of non-Hodgkin lymphoma (NHL), but long-term risk and time trends have seldom been evaluated. Immunosuppressive drug load is an important risk determinant, but the details are unclear. We studied NHL risk in a nationwide Swedish cohort of 11 081 graft recipients transplanted 1970-2008. Relative risks (RRs) were estimated within the cohort and versus the general population by age, sex, follow-up time and calendar period. NHL risk was also assessed by cumulative and average doses of immunosuppressive treatments in a nested case-control design throughout 1997 using conditional logistic regression. We observed 153 NHL cases during 97 853 years of follow-up. Compared with the general population, NHL risk was eightfold increased (RR 7.9; 95% confidence interval [CI] 6.6-9.4), and increased risks persisted after >= 15 years of follow-up among kidney (6.1; 95% CI 3.5-10) and nonkidney recipients (44; 14-103). Among nonkidney recipients, NHL risk was lower in the 2000s compared with the 1990s (0.5; 95% CI 0.3-1.0; p = 0.04). A high average dose of antithymocyte immunoglobulin (ATG) conferred an eightfold increased risk of NHL (OR 8.5; 95% CI 1.9-38). To conclude, posttransplant NHL risk decreased during the last decade among nonkidney recipients, possibly because of a more careful use of ATG, the introduction of new drugs, or both.
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  • Glimelius, Ingrid, et al. (författare)
  • Long-term survival in young and middle-aged Hodgkin lymphoma patients in Sweden 1992-2009 - trends in cure proportions by clinical characteristics.
  • 2015
  • Ingår i: American Journal of Hematology. - : Wiley. - 0361-8609 .- 1096-8652. ; 90:12, s. 1128-1134
  • Tidskriftsartikel (refereegranskat)abstract
    • Trends in Hodgkin lymphoma (HL) survival among patients treated outside of clinical trials provide real-world benchmark estimates of prognosis and help identify patient subgroups for targeted trials. In a Swedish population-based cohort of 1947 HL patients diagnosed 1992-2009 at ages 18-59 years, we estimated relative survival (RS), cure proportions (CP) and median survival times using flexible parametric cure models. Overall, the CP was 89% (95%CI:0.87-0.91) and median survival of the uncured was 4.6 years (95%CI:3.0-6.3). For patients aged 18-50 years diagnosed after the year 2000, CP was high and stable, whereas for patients 50-59 years cure was not reached. The survival of relapse-free patients was similar to that of the general population (RS5-year :0.99; 95%CI:0.98-0.99, RS15-year :0.95; 95%CI:0.92-0.97). The excess mortality of relapsing patients was 19 times (95%CI:12-31) that of relapse-free patients. Despite modern treatments, patients with adverse prognostic factors (e.g., advanced stage) still had markedly worse outcomes [CPstage:IIIB 0.82 (95%CI:0.73-0.89); CPstage:IVB 0.72, (95%CI:0.60-0.81)] and patients with international prognostic score (IPS) ≥3 had 2.7 times higher excess mortality (95%CI:1.0-7.0, p=0.04) than patients with IPS <3. High-risk patients selected for 6-8 courses of BEACOPP (bleomycin, etoposide, doxorubicin, cyclofosphamide, vincristine, procarbazine, prednisone)-chemotherapy had a 15-year relative survival of 87%, (95%CI:0.80-0.92), whereas the corresponding estimate for patients selected for 6-8 courses of ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) was 93% (95%CI:0.88-0.97). These population-based results indicate limited fatal side-effects in the 15-year perspective with contemporary treatments, while the unmet need of effective relapse treatment remains of concern. BEACOPP-chemotherapy was still not sufficient in high-risk HL patients. This article is protected by copyright. All rights reserved.
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  • Glimelius, Ingrid, et al. (författare)
  • Sick leave and disability pension in Hodgkin lymphoma survivors by stage, treatment, and follow-up time-a population-based comparative study
  • 2015
  • Ingår i: Journal of Cancer Survivorship. - : Springer Science and Business Media LLC. - 1932-2267 .- 1932-2259. ; 9:4, s. 599-609
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose This study seeks to investigate the long-term public health burden of Hodgkin lymphoma (HL) in terms of work loss following contemporary treatment protocols and associations with established treatment complications and lymphoma relapse. Methods We identified 1,989 Swedish HL patients (1,082 with clinical information) aged 18-60 (median 33) years at diagnosis 1992-2009, and matched 1:4 to population comparators. Sick leave, disability pension (work loss), and comorbidity were retrieved through September 2013. Relative risks (RR) with 95 % confidence intervals (CI) were calculated using Poisson regression, and mean lost work days were estimated yearly during follow-up. Results The risk of annual work loss was elevated in HL survivors versus comparators up to the 15th year post-diagnosis (RR5th year 1.64, 95 % CI 1.46-1.84; RR10th year 1.33, 95 % CI 1.15-1.34; and RR15th year 1.30, 95 % CI 1.04-1.62). The risk remained elevated up to the 10th year after adjustment for secondary malignancies and cardiovascular disease (RR10th year 1.31, 95 % CI 1.13-1.52). Advanced-stage patients had more lost days than comparators (mean number(5th year) 66 versus 33, mean difference 34, 95 % CI 20-48) as did patients receiving 6-8 chemotherapy courses (62 versus 33, mean difference(5th year) 30, 95 % CI 17-43). Among patients in the first complete remission, a difference was still observed for advanced-stage (51 versus 33, mean difference(5th year) 19, 95 % CI 5-34) but not early-stage disease. Conclusions Advanced-stage HL survivors treated with full-dose chemotherapy were at increased risk of work loss, not only explained by relapse, secondary malignancies, or cardiovascular disease.
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  • Harrysson, S., et al. (författare)
  • Incidence of relapsed/refractory diffuse large B-cell lymphoma (DLBCL) including CNS relapse in a population-based cohort of 4243 patients in Sweden
  • 2021
  • Ingår i: Blood Cancer Journal. - : Springer Science and Business Media LLC. - 2044-5385. ; 11:1
  • Tidskriftsartikel (refereegranskat)abstract
    • We performed a national population-based study of all patients diagnosed with diffuse large B-cell lymphoma (DLBCL) in Sweden in 2007-2014 to assess treatment intent and risk of relapsed/refractory disease, including central nervous system (CNS) relapse, in the presence of competing risks. Overall, 84% of patients started treatment with curative intent (anthracycline-based) (n=3550, median age 69 years), whereas 14% did not (n=594, median age 84 years) (for 2% the intent was uncertain). Patients treated with curative intent had a 5-year OS of 65.3% (95% CI: 63.7-66.9). The median OS among non-curatively treated patients was 2.9 months. The 5-year cumulative incidence of relapsed/refractory disease in curative patients was 23.1% (95% CI: 21.7-24.6, n=847). The 2-year cumulative incidence of CNS relapse was 3.0% (95% CI: 2.5-3.6, n=118) overall, and 8.0% (95% CI: 6.0-10.6, n=48) among patients with high CNS-IPI (4-6), when considering other relapse locations and death as competing events. The incidence of relapsed/refractory DLBCL overall and in the CNS was lower than in previous reports, still one in seven patients was not considered fit enough to start standard immunochemotherapy at diagnosis. These results are important for quantification of groups of DLBCL patients with poor prognosis requiring completely different types of interventions.
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  • Harrysson, S., et al. (författare)
  • Outcomes of relapsed/refractory diffuse large B-cell lymphoma and influence of chimaeric antigen receptor T trial eligibility criteria in second line-A population-based study of 736 patients
  • 2022
  • Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 198:2, s. 267-277
  • Tidskriftsartikel (refereegranskat)abstract
    • Several recently published trials investigate novel therapies for relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL). To estimate the benefit of these therapies in the real-world setting, comprehensive data on patients treated in clinical routine are needed. We report outcomes for 736 R/R DLBCL patients identified among all curatively treated DLBCL patients in Sweden in the period 2007-2014. Survival and associations with disease characteristics, second-line treatment and fulfilment of chimaeric antigen receptor (CAR) T-cell trial criteria were assessed. Median overall survival (OS) was 6.6 months (<= 70 years 9.6 months, >70 years 4.9 months). Early relapse (<= 12 months) was strongly associated with selection of less intensive treatment and poor survival. Among patients of at most 70 years of age, 63% started intensive second-line treatment and 34% received autologous stem cell transplantation (ASCT). Two-year OS among transplanted patients was 56% (early relapse <= 12 months 40%, late relapse >12 months 66%). A minority of patients 76 years (n = 178/506, 35%) fitted CAR T trial criteria. Median progression-free survival (PFS) for patients with early relapse fitting trial criteria was 4.8 months. In conclusion, most R/R DLBCL manifest early and are often ineligible for or cannot complete intensive regimens resulting in dismal survival. Real-world patients eligible for CAR T trials also did poorly, providing a benchmark for efficacy of novel therapies.
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  • Hellgren, K., et al. (författare)
  • Ankylosing Spondylitis, Psoriatic Arthritis, and Risk of Malignant Lymphoma : A Cohort Study Based on Nationwide Prospectively Recorded Data From Sweden
  • 2014
  • Ingår i: Arthritis & Rheumatology. - : Wiley. - 2326-5191 .- 2326-5205. ; 66:5, s. 1282-1290
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective. Data on lymphoma risk in ankylosing spondylitis (AS) and psoriatic arthritis (PsA) are scarce. This study was undertaken to assess the risk of lymphoma in AS and PsA overall and in relation to therapies, including tumor necrosis factor inhibitor (TNFi), for which lymphoma risks are a concern. Methods. Through the Swedish National Patient Register we assembled nationwide prevalence cohorts of patients with AS (n = 8,707) and patients with PsA (n = 19,283) for whom data were obtained between 2001 and 2010. Each cohort member was matched to 5 population comparator subjects. Linkage with the nationwide Cancer Register identified all lymphomas recorded from 2001 to 2010. Through the Swedish Biologics Register (Anti-Rheumatic Therapy in Sweden [ARTIS]), we identified patients exposed to TNFi in the AS cohort (n = 1,908) and the PsA cohort (n = 2,605) before lymphoma diagnosis. Hazard ratios (HRs) for lymphoma were estimated by Cox regression. Crude incidences of lymphoma in TNFi-exposed and TNFi-naive patients were compared. Results. For AS patients, the HR of having lymphoma versus the general population was 0.9 (95% confidence interval [95% CI] 0.5-1.6) (14 lymphomas). For PsA patients, the corresponding HR was 1.2 (95% CI 0.9-1.7) (45 lymphomas). For PsA patients treated with methotrexate and/or sulfasalazine, the HR of having lymphoma was 1.7 (95% CI 1.0-3.1). The numbers and incidence of lymphoma were not materially different in TNFi-exposed versus TNFi-naive AS and PsA patients, although the numbers of lymphomas were small. Conclusion. In contrast to rheumatoid arthritis, the average risks of lymphoma in AS or PsA are not elevated, although increased risks in a subset of PsA patients cannot be excluded. Our findings indicate that TNFi does not affect the risk of lymphoma in AS or in PsA.
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  • Hellgren, K., et al. (författare)
  • Rheumatoid Arthritis and Risk of Malignant Lymphoma - Is the risk still increased?
  • 2017
  • Ingår i: Arthritis & Rheumatology. - : Wiley. - 2326-5191 .- 2326-5205. ; 69:4, s. 700-708
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: Patients with rheumatoid arthritis (RA) are at increased risk of malignant lymphomas with a strong correlation with RA disease severity. Given the changes in RA therapy over recent decades, we aimed at assessing whether lymphoma risk remains increased, and if so, to explore risk predictors and lymphoma subtypes.METHODS: We identified 12,656 incident RA patients from the Swedish Rheumatology Register 1997-2012 including information on therapy and inflammatory activity during the first year following diagnosis. Each patient was matched to 10 population comparator subjects. Through linkage to the Swedish Cancer Register, lymphomas including subtypes were identified. We assessed Hazard ratios (HRs) using Cox regression.RESULTS: Overall, the HR of lymphoma was increased, 1.6, 95% confidence interval [CI] 1.2-2.1. Taking RA duration into account, risks did not appear to have declined over successive calendar years of RA diagnosis. Neither use of methotrexate the 1(st) year following RA diagnosis nor ever use of TNF inhibitors (HR=0.9; 95% CI 0.4-1.9) increased lymphoma risk. Use of oral corticosteroids the 1(st) year following RA diagnosis was associated with a reduced risk (HR=0.6; 95% CI 0.5 -0.9). Inflammatory activity during the 1(st) year following RA diagnosis did not predict future lymphoma risk. Chronic lymphocytic lymphoma occurred less, and Hodgkin lymphoma more frequently than expected compared to the general population.CONCLUSION: The average lymphoma risk in recently diagnosed RA is of similar magnitude as that reported from historical cohorts. Standard anti-rheumatic treatment including TNF inhibitors did not predict future lymphoma risk. Distribution of lymphoma subtypes warrants further investigation.
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  • Krynitz, B., et al. (författare)
  • Risk of basal cell carcinoma in Swedish organ transplant recipients: a population-based study
  • 2016
  • Ingår i: British Journal of Dermatology. - : WILEY-BLACKWELL. - 0007-0963 .- 1365-2133. ; 174:1, s. 95-103
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Risk of basal cell carcinoma (BCC) has been reported to be several-fold increased among organ transplant recipients (OTRs). However, due to lack of reliable BCC registration, population-based risk estimates are scarce. Objectives To characterize risk of BCC among OTRs compared with the general population, and contrast with risk of cutaneous squamous cell carcinoma (SCC). Subjects and methods OTRs transplanted during 2004-2011 were identified through national healthcare registers and linked with the nationwide Swedish BCC Register initialized in 2004. Relative risk of BCC was expressed as standardized incidence ratios (SIR) with 95% confidence intervals (CI). Results Altogether, 4023 transplanted patients developed 341 BCCs during follow-up. Compared with the general population, the relative risk of BCC was increased sixfold (SIR 6.1, 95% CI 5.4-6.9). The risk was higher in kidney and heart/lung than in liver recipients (SIRkidney 7.2, 6.3-8.3; SIRheart/lung 5.8, 4.0-8.2; SIRliver 2.6, 1.7-4.0), and risk increased with time since transplantation (P-trend < 0.01). The SCC to BCC ratio was 1 : 1.7 and BCC developed earlier after transplantation than SCC. Distribution of anatomical sites and histological types did not differ substantially between OTR- and population-BCCs. Conclusions Risk of BCC was strikingly elevated in OTRs compared with the general population. Risk was higher in kidney recipients and increased with follow-up time. These findings support a tumour-promoting effect of immunosuppressive drugs in BCC development. The low SCC to BCC ratio was possibly attributed to short follow-up time.
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26.
  • Ludvigsson, Jonas F., 1969-, et al. (författare)
  • Prevalence of paediatric inflammatory bowel disease in Sweden : a nationwide population-based register study
  • 2017
  • Ingår i: BMC Gastroenterology. - London, England : BioMed Central. - 1471-230X. ; 17
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: We evaluated the impact of different case definition algorithms on the prevalence of paediatric inflammatory bowel disease (IBD), Crohn's disease (CD) and ulcerative colitis (UC) and to compare the occurrence of certain diseases compared to matched controls.Methods: Paediatric patients (<18 years) were identified via ICD codes for UC and CD in Swedish registers between 1993 and 2010 (n = 1432). Prevalence was defined as >= 2 IBD-related visits. Prevalence of treated children in 2010 was defined as >= 2 IBD-related visits with one visit and >= 1 dispensed IBD-related drug prescription in 2010. To test the robustness of the estimates, prevalence was also calculated according to alternative case definitions. The presence of rheumatic, hepatobiliary, pancreatic, and dermatologic diseases were compared with age-/sex-/county-of-residence- matched general population controls.Results: The IBD prevalence was 75/100,000 (CD: 29/100,000; UC: 30/100,000; patients with IBD-U: 16/100,000). Prevalence of treated disease in 2010 was 62/100,000 (CD: 23/100,000; UC: 25/100,000; patients with IBD-U: 13/100,000). When age restrictions were employed, the prevalence estimate decreased (<17y: 61/100,000, <16y: 49/100,000 and <15y: 38/100,000).Compared to general population controls (n = 8583), children with IBD had a higher prevalence of dermatologic (4.7% vs. 0.6%), hepatobiliary (including primary sclerosing cholangitis) (5.5% vs. 0.1%), pancreatic (1.7% vs. 0%) and rheumatic diseases (7.2% vs. 1.2%; all P < 0.01).Conclusions: The overall prevalence of paediatric IBD in Sweden was similar to that in earlier regional cohorts. IBD patients had a higher prevalence of comorbid conditions than matched general population controls.
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27.
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28.
  • Martling, A., et al. (författare)
  • Risk of second primary cancer in patients treated with radiotherapy for rectal cancer
  • 2017
  • Ingår i: British Journal of Surgery. - : Oxford University Press (OUP). - 0007-1323 .- 1365-2168. ; 104:3, s. 278-287
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Many patients with rectal cancer receive radiotherapy (RT) to reduce the risk of local recurrence. Radiation may give rise to adverse effects, including second primary cancers. In view of the divergent results of previous studies, the present study evaluated the risk of second primary cancer following RT in all randomized RT rectal cancer trials conducted in Sweden and in the Swedish ColoRectal Cancer Registry (SCRCR).Methods: Patients included in five randomized trials and the SCRCR were linked to the Swedish Cancer Registry. Cox regression models estimated the hazard ratio (HR) of second primary cancer among patients who received RT compared with those who did not.Results: A total of 13 457 patients were included in this study; 7024 (52.2 per cent) received RT and 6433 (47.8 per cent) had surgery alone. Overall, no increased risk of second primary cancer was observed with RT (HR 1.03; 95 per cent c. i. 0.92 to 1.15), independently of follow-up time and location within or outside of the irradiated volume. In the randomized trials, with longer follow-up (maximum 31 years), a slight increase was observed outside of (HR 1.33, 1.01 to 1.74) but not within (HR 1.11, 0.73 to 1.67) the irradiated volume. Irradiated men had a lower risk of prostate cancer than those treated with surgery alone (HR 068, 0.51 to 091).Conclusion: Overall, there was no increased risk of second primary cancer following RT for rectal cancer within or outside of the irradiated volume up to 20 years of follow-up. Men with rectal cancer who received RT had a reduced risk of prostate cancer.
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29.
  • Mohammadi, M., et al. (författare)
  • Risk of lymphoid neoplasms in a Swedish population-based cohort of 337,437 patients undergoing appendectomy
  • 2016
  • Ingår i: Scandinavian Journal of Gastroenterology. - Oxon, United Kingdom : Taylor & Francis. - 0036-5521 .- 1502-7708. ; 51:5, s. 583-589
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Appendectomy remains one of the most common surgical procedures, but possible long-term consequences for health and disease are incompletely investigated. The appendix forms part of the secondary lymphoid system and appendectomy has been associated with increased risks of hematolymphoproliferative malignancies in some studies.Materials and methods: We examined the risk of lymphoid neoplasms in a large cohort of 337,437 appendectomised patients <60 years of age in Sweden 1975-2009. We estimated relative risks of non-Hodgkin lymphoma (NHL) and major subtypes, Hodgkin lymphoma (HL), chronic lymphocytic leukaemia (CLL), myeloma, and acute lymphoblastic leukaemia (ALL) versus the general population using standardised incidence ratios (SIRs) with 95% confidence intervals (CIs).Results: There was no increased risk of NHL (SIR = 0.97, 95%CI 0.88-1.06), major NHL subtypes, CLL (SIR = 0.87, 95%CI 0.70-1.06), myeloma (SIR = 1.14, 95%CI 0.96-1.33) or ALL (SIR = 1.10, 95%CI 0.80-1.47) following appendectomy. An increased risk of HL was observed among patients diagnosed with appendicitis (SIR = 1.29, 95%CI 1.07-1.54, p=0.007), especially individuals aged <20 years at surgery (SIR = 1.43, 95%CI 1.11-1.82), and for the nodular sclerosis subtype of HL (SIR = 1.55, 95%CI 1.01-2.27). A marginally increased risk of myeloma was noted among men, but the association was limited to the first few years of follow-up.Conclusion: Appendectomy is not associated with any notable increase in risk of lymphoid neoplasms. A small increased risk of HL following appendicitis (rather than appendectomy per se) could reflect a true association, or shared susceptibility to infection/inflammation among individuals prone to develop HL. The association observed for myeloma may be explained by chance or surveillance bias.
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30.
  • Nordenvall, C., et al. (författare)
  • Probability, rate and timing of reconstructive surgery following colectomy for inflammatory bowel disease in Sweden: a population-based cohort study
  • 2015
  • Ingår i: Colorectal Disease. - : WILEY-BLACKWELL. - 1462-8910 .- 1463-1318. ; 17:10, s. 882-890
  • Tidskriftsartikel (refereegranskat)abstract
    • Aim Many patients with inflammatory bowel disease (IBD) need colectomy, but the rate of reconstructive surgery with restoration of intestinal continuity is unknown. The aim of this study was to investigate the probability, rate and timing of reconstructive surgery after colectomy in patients with IBD in a population-based setting. Method The study cohort included all patients with IBD in Sweden who underwent colectomy from 2000 to 2009. Each patient was followed from admission for colectomy to admission for reconstructive surgery, date of death, migration or 31 December 2010. Kaplan-Meier survival curves and multivariable Poisson regression models were used to describe the probability, rate and timing of reconstructive surgery. Results Out of 2818 IBD patients treated with colectomy, 61.0% were male and 78.9% had ulcerative colitis. No reconstructive surgery had been performed in 1595 (56.6%) patients by the end of follow-up. Of the remaining 1223 patients, 526 underwent primary reconstructive surgery and 697 had a secondary reconstruction following a median interval of 357 days from primary surgery in the form of colectomy. The probability of reconstructive surgery was dependent on age (55.6% and 18.1% at ages 15-29 and greater than= 59 years, respectively), and the chance of reconstructive surgery was higher in hospitals that performed more than 13 colectomies for IBD per year [incidence rate ratio and 95% confidence interval 1.27 (1.09-1.49)]. Conclusion Fewer than half of the patients having a colectomy for IBD underwent subsequent reconstructive surgery. Older age and low hospital volume were risk factors for no reconstructive surgery.
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31.
  • Petersson, Josefin, et al. (författare)
  • Increasing incidence of colorectal cancer among the younger population in Sweden
  • 2020
  • Ingår i: Bjs Open. - : Oxford University Press (OUP). - 2474-9842. ; 4:4, s. 645-658
  • Tidskriftsartikel (refereegranskat)abstract
    • Background The incidence of colorectal cancer in patients aged less than 50 years is increasing in Western countries. This population-based study investigated the age- and sex-specific incidence of colorectal cancer over time in Sweden, and characterized trends in tumour localization and stage at diagnosis. Methods Patients diagnosed with colorectal cancer between 1970 and 2016 were identified from the Swedish Cancer Registry, and categorized by sex, age and tumour location. The incidence and average annual percentage change (AAPC) were estimated and compared between age groups. Results There was an overall increase in the incidence of colorectal cancer between 1970 and 2006, but a decrease in 2006-2016 (AAPC -0.55 (95 per cent c.i. -1.02 to -0.07) per cent). The largest increase in colonic cancer was in 1995-2005 in women aged less than 50 years (AAPC 2.30 (0.09 to 4.56) per cent versus 0.04 (-1.35 to 1.44) and - 0.67 (-1.62 to 0.28) per cent in women aged 50-74 and 75 years or more respectively). Since 1990, rectal cancer increased in patients of both sexes aged below 50 years, with higher AAPC values in women (2006-2016: 2.01 (-1.46 to 5.61) per cent versus 0.20 (-2.25 to 2.71) per cent in men). Younger patients were more likely than those aged 50-74 and 75 years or more to present with stage III-IV colonic (66.2, 57.6 and 49.6 per cent respectively) and rectal (61.2, 54.3 and 51.3 per cent) cancer. From the mid 1990s, rates of proximal and distal colorectal cancer, and rectal cancer were increased in patients aged less than 50 years. Conclusion The overall incidence of colorectal cancer in Sweden decreased in the past decade. However, in patients under 50 years of age the incidence of colorectal cancer - proximal, distal and rectal - continued to increase over time.
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32.
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33.
  • Simard, J. F., et al. (författare)
  • Pediatric Organ Transplantation and Risk of Premalignant and Malignant Tumors in Sweden
  • 2011
  • Ingår i: American Journal of Transplantation. - : Elsevier BV. - 1600-6135 .- 1600-6143. ; 11:1, s. 146-151
  • Tidskriftsartikel (refereegranskat)abstract
    • Increased cancer risks are well documented in adult organ transplant recipients. However, the spectrum of malignancies and risk in the pediatric organ transplant population are less well described. We identified all solid organ transplanted patients aged < 18 in Sweden between 1970-2007 (n = 536) in the National Patient Register and linked to the Cancer Register. Nationwide rates were used to calculate standardized incidence rate ratios and 95% CI estimating the association between transplant and cancer during maximum 36 years of follow-up. Nearly 7% of pediatric solid organ transplant recipients developed a premalignant or malignant tumor during follow-up. Transplantation was associated with an increased risk of any cancer (n = 24, SIR = 12.5, 95% CI: 8.0-18.6): non-Hodgkin lymphoma (NHL) (n = 13, SIR = 127, 95% CI: 68-217), renal cell (n = 3, SIR = 105, 95% CI: 22-307), vulva/vagina (n = 3, SIR = 665, 95% CI: 137-1934) and nonmelanoma skin cancers (n = 2, SIR = 64.7, 95% CI: 7.8-233.8). NHL typically appeared during childhood, while other tumors were diagnosed during adulthood. Apart from short-term attention toward the potential occurrence of NHL, our results suggest cancer surveillance into adulthood with special attention to skin, kidneys and the female genitalia.
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34.
  • Smedby, K. E., et al. (författare)
  • Autoimmune and inflammatory disorders and risk of malignant lymphomas : an update
  • 2008
  • Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 264:6, s. 514-527
  • Forskningsöversikt (refereegranskat)abstract
    • As specific autoimmune disorders now constitute established risk factors for malignant lymphomas, we describe this association.We review reported risk levels, risk determinants, lymphoma subtypes and biological mechanisms in autoimmunity/inflammation, emphasizing on recent findings.Whilst numerous reports describe average lymphoma risks in large patient groups, there's a recent shift of focus to risk determinants and the role of inflammatory activity. Studies highlight associations with diffuse large B-cell lymphoma, apart from lymphoma development in target organs of inflammation.Future studies of high-risk patient subsets using detailed assessments of autoimmunity/inflammation and lymphoma may give important clues to lymphomagenesis.
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35.
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36.
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37.
  • Vasaitis, Lilian, et al. (författare)
  • Comparison of patients with and without pre-existing lymphoma at diagnosis of primary Sjögren's syndrome
  • 2019
  • Ingår i: Scandinavian Journal of Rheumatology. - : Informa UK Limited. - 0300-9742 .- 1502-7732. ; 48:3, s. 207-212
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: In the 2016 American College of Rheumatology/European League Against Rheumatism classification criteria for primary Sjögren's syndrome (pSS), pre-existing lymphoma is not an exclusion criterion for pSS diagnosis, as in earlier criteria. We aimed to explore whether there are differences between pSS patients with and without pre-existing lymphoma at pSS diagnosis.METHOD: Patients with ICD-7-10 codes for Sjögren's syndrome (SS) and a diagnosis of malignant lymphoma before or after SS diagnosis were identified by linking the Swedish Patient Register 1964-2007 with the Cancer Register 1990-2007 (n = 224). Clinical data were collected from medical records. Lymphoma diagnoses were evaluated by tissue review. Characteristics of pSS patients with and without pre-existing lymphoma were compared.RESULTS: We identified 107 patients with pSS as the reason for an SS diagnosis code and a verified lymphoma. Of these, 18 (17%) had a pre-existing lymphoma at pSS diagnosis, defined as lymphoma diagnosed before or within 6 months of pSS diagnosis. Male gender (39% vs 10%, p = 0.006), enlarged lymph nodes during the pSS disease (61% vs 27%, p = 0.01), mucosa-associated lymphoid tissue (MALT) lymphoma (50% vs 22%, p = 0.02), and salivary gland lymphoma (61% vs 26%, p = 0.006) were more common in patients with a pre-existing lymphoma at pSS diagnosis. Other pSS characteristics were similar.CONCLUSION: In a substantial proportion of patients, particularly in men, pSS remains undiagnosed until after lymphoma diagnosis. The study highlights the importance of pSS investigation in patients with lymphoma, especially MALT lymphoma, in the salivary glands.
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38.
  • Vasaitis, Lilian, et al. (författare)
  • Population-based study of patients with primary Sjögren’s syndrome and lymphoma : lymphoma subtypes, clinical characteristics, and gender differences
  • 2020
  • Ingår i: Scandinavian Journal of Rheumatology. - : Informa UK Limited. - 0300-9742 .- 1502-7732. ; 49:3, s. 225-232
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To examine lymphoma subtypes, clinical characteristics, and gender differences in patients with primary Sjögren’s syndrome (pSS) and lymphoma in a population-based setting. Method: Patients with Sjögren’s syndrome and lymphoma diagnoses were identified by linkage of the Swedish Patient Register 1964–2007 with the Cancer Register 1990–2007. Clinical data were collected from medical records and lymphoma tissues were re-examined. The lymphoma subtype distribution was compared with the Swedish Lymphoma Register. Results: We identified 105 pSS patients with lymphoma. Diffuse large B-cell lymphoma (DLBCL) (32%) and marginal zone lymphoma [MZL including mucosa-associated lymphoid tissue (MALT) lymphoma] (31%) were the most common lymphoma subtypes. The proportion of DLBCL was not increased compared to the general population reference (32%, p = 1), in contrast to MZL (general population 5%, p < 0.0001). Compared to DLBCL, MALT lymphoma was diagnosed at a younger age (55 vs 67 years, p = 0.0001), and earlier after patient-reported sicca onset (7 vs 18 years, p = 0.0001) and pSS diagnosis (2 vs 9 years, p = 0.0005). Sixteen of the pSS-lymphoma cases were men (15%), twice the proportion in general pSS populations. Compared to women, men had a shorter median time from pSS diagnosis to lymphoma diagnosis (1 vs 8 years, p = 0.0003) and more often had lymphoma in the salivary glands (56% vs 29%, p = 0.04). Conclusion: DLBCL and MZL are common in pSS patients, but only MZL/MALT lymphoma occurs at an increased relative frequency in pSS compared to the general population. The study supports increased awareness of signs of lymphoma in men in the first years after pSS diagnosis.
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39.
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40.
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41.
  • Wästerlid, T., et al. (författare)
  • Impact of comorbidity on disease characteristics, treatment intent and outcome in diffuse large B-cell lymphoma : a Swedish lymphoma register study
  • 2019
  • Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 285:4, s. 455-468
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundComorbidity impacts overall survival amongst patients with diffuse large B-cell lymphoma (DLBCL). However, associations of comorbidity with lymphoma characteristics, treatment selection and lymphoma-specific mortality are less well known.ObjectiveTo examine the impact of comorbidity on DLBCL characteristics, treatment intent and cause of death.MethodsWe identified 3905 adult patients diagnosed with DLBCL 2007-2013 through the Swedish Lymphoma Register. We assessed comorbid disease history according to the Charlson comorbidity index (CCI). Comorbidity data and causes of death were collected through register linkage. Associations were estimated using multinomial regression and flexible parametric survival models.ResultsOverall, 45% of the patients (n = 1737) had a history of at least one comorbidity at DLBCL diagnosis (cardiovascular disease, diabetes and solid cancer were most frequent), and 997 (26%) had a CCI score of 2. The relative probability of presenting with poor performance status (PS > 2) was higher amongst comorbid patients [Relative Risk Ratio (RRR)(PS>2): 2.02, 95% CI: 1.63-2.51]. Comorbid patients had a substantially lower relative probability of receiving curative treatment (RRR: 0.48, 95% CI: 0.38-0.61). Amongst all patients, CCI 1 was associated with a significantly increased risk of all-cause and lymphoma-specific death after adjustments. Amongst patients selected for curative treatment, comorbidity was associated with an increased risk of all-cause death (HRCCI>1: 1.54, 95% CI: 1.32-1.80), but not with lymphoma-specific death (HRCCI>1: 1.05, 95% CI: 0.86-1.28).ConclusionComorbidity is associated with inferior DLBCL outcome, mainly due to a lower likelihood of receiving treatment with curative intent. Possibly, more comorbid DLBCL patients could be treated with curative intent if comorbid conditions were optimized in parallel.
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42.
  • Wästerlid, Tove, et al. (författare)
  • Outcome and determinants of failure to complete primary R-CHOP treatment for reasons other than non-response among patients with diffuse large B-cell lymphoma
  • 2020
  • Ingår i: American Journal of Hematology. - : Wiley. - 0361-8609 .- 1096-8652. ; 95:7, s. 740-748
  • Tidskriftsartikel (refereegranskat)abstract
    • Patients with diffuse large B-cell lymphoma (DLBCL) who fail to complete planned treatment with R-CHOP due to toxicity are sparsely described. We investigated the extent of failure to complete treatment (six cycles or more, or three cycles + RT for patients with stage I disease) with R-CHOP for reasons unrelated to non-response, the determinants of such failure and the outcome among these patients. Three thousand one hundred and forty nine adult DLBCL patients who started primary treatment with R-CHOP were identified through the Swedish lymphoma register 2007-2014. Of these, 147 (5%) stopped prematurely after 1-3 cycles of R-CHOP for reasons unrelated to non-response, 168 (5%) after 4-5 cycles and 2639 patients (84%) completed planned treatment. Additionally, 195 (6%) patients did not complete treatment due to non-response or death before treatment end. In a multivariable logistic regression model, age > 75 years, poor performance status, extranodal disease and Charlson Comorbidity Index >= 1 were significantly associated with failure to complete planned R-CHOP treatment for other reasons than non-response. Non-completion of treatment strongly correlated with survival. Five-year overall survival for patients who received 1-3 cycles was 26% (95% CI: 19%-33%), 49% (95% CI: 41%-57%) for 4-5 cycles and 76% (74%-77%) for patients who completed treatment. Failure to complete planned R-CHOP treatment is an important clinical issue associated with inferior survival. Old age and poor performance status most strongly predict such failure. These results indicate a need for improved treatment tailoring for patients with certain baseline demographics to improve tolerability and chance for treatment completion.
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