Background
Previous studies have suggested an association between season of birth and risk of childhood asthma and allergic disease. The association may be modified by birth year and region, or ...mediated by respiratory tract infections.
Objective
We aimed to estimate the association between season of birth and risk of childhood asthma/wheeze or allergic rhinoconjunctivitis in a population‐based setting, and the mediating effect of lower respiratory infections.
Methods
Two population‐based cohorts were identified from the nationwide Swedish Medical Birth, Patient and Prescribed Drug Registers. The association between birth month/season and asthma/wheeze incidence was analysed using Cox proportional regression in the younger cohort born 2005‐2010 (n = 582 494) and asthma/allergic rhinoconjunctivitis prevalence during the 7th year of life using log‐binomial models in the older cohort born 2001‐2004 (n = 367 583). Interactions were formally tested. Mediation analyses to address the effect of lower respiratory infections were performed in the older cohort using the R package “medflex.”
Results
Children born during fall and winter had an increased risk of asthma/wheeze after 2 years of age in the younger cohort: hazard ratio 1.24 (95% confidence interval, CI 1.17, 1.33) for winter and risk of prevalent asthma during their 7th year of life in the older cohort; prevalence ratio (PR) 1.12 (95% CI 1.08, 1.16) for winter. These estimates were partly mediated by lower respiratory infections; the indirect effect for winter compared with summer was PR 1.03 (95% CI 1.03, 1.04). The association was similar for allergic rhinoconjunctivitis in the 7th year of life, but not mediated by respiratory infections.
Conclusion
We found that the association between season of birth and risk of childhood asthma/wheeze, but not allergic rhinoconjunctivitis, is partly mediated through lower respiratory infections.
Clinical relevance
This has important implications for patient care, such as asthma management programmes to notify timing of seasonality for viral respiratory tract infections.
Results from previous studies indicate that use of low-dose aspirin may improve breast cancer prognosis. We evaluated aspirin use and breast cancer outcomes in relation to clinical characteristics as ...well as dose and duration of aspirin use.
We used information from the Regional Breast Cancer Quality-of-Care Registries in three Swedish regions to identify 21,414 women diagnosed with a first stage I-III breast cancer between 1 April 2006 and 31 December 2012. The cohort was further linked to nationwide registers to retrieve information about dispensing low-dose aspirin before and after breast cancer diagnosis, comorbidity and causes of death. In a separate analysis, we investigated time to breast cancer death among 621 women with stage IV disease at diagnosis. Associations were evaluated using a multivariable Cox proportional hazards model.
Among women with stage I-III breast cancer, 2660 (12.4%) used low-dose aspirin shortly before breast cancer diagnosis and 4091 (19.1%) were users during follow-up. Women were followed for a median of 3.8 years after diagnosis. There was no association between aspirin use and breast cancer-specific death in multivariable analyses (use before diagnosis: hazard ratio (HR) 0.93, 95% confidence interval (CI) 0.77-1.12; use after diagnosis: HR 1.00, 95% CI 0.74-1.37). Similarly, aspirin use was not associated with risk of first recurrence/metastases in a subgroup of stage I-III breast cancer patients (HR 0.97, 95% CI 0.86-1.10). However, in analyses stratified by stage, an inverse association between low-dose aspirin use after diagnosis and breast cancer death was found for women with stage I tumors (HR 0.53, 95% CI 0.29-0.96). Among women with stage IV disease at diagnosis, aspirin use was not associated with time to breast cancer death (HR 0.91, 95% CI 0.67-1.23).
In this large population-based cohort study there was no evidence that low-dose aspirin use before or after breast cancer diagnosis is associated with a reduced risk of adverse outcomes overall in breast cancer. However, a potential benefit was noted among women with stage I tumors, warranting further investigation.
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.
•The use of RT in lymphoma has not decreased during the recent decade.•Use of RT as monotherapy is most often applied to patients aged > 80 years or with limited-stage disease.•Relative survival is ...encouraging for lymphoma patients selected for RT monotherapy.
The role of radiotherapy (RT) in lymphoma is constantly refined with the advent of novel treatments. However, RT is still an effective treatment and tolerability is high. Therefore, we aimed to describe the use of RT in primary treatment of lymphoma over calendar time, with a specific focus on older patients (age ≥ 70 years) with non-Hodgkin lymphoma (NHL) subtypes.
All adult patients diagnosed with lymphoma from 2007 to 2018 in Sweden were included and followed for survival until end of 2020. Patient characteristics and relative survival (RS) were described for patients with NHL by subtype and RT use.
In the cohort of lymphoma patients aged ≥ 70 years (n = 12,698) 11 % received RT as part of primary treatment. No decline in use of RT over calendar period was seen. Use of RT as monotherapy was associated with stage I-II disease and older age among patients with stage III-IV disease. Patients with indolent lymphomas aged ≥ 70 years who were selected for treatment with RT as monotherapy with a dose of ≥ 20 Gy had 2-year RS rate of 100 % which remained similar at five years. For patients with DLBCL, RT as monotherapy with a dose of ≥ 20 Gy was mostly administered to patients aged ≥ 85 years with a 2-year RS rate of 68 %.
The use of RT in first-line lymphoma treatment was stable over calendar time. RT monotherapy is associated with encouraging outcomes among patients with NHL aged ≥ 70 years who were selected to receive this.
The aim of this data paper is to describe a collection of 33 genomic, transcriptomic and epigenomic sequencing datasets of the B-cell acute lymphoblastic leukemia (ALL) cell line REH. REH is one of ...the most frequently used cell lines for functional studies of pediatric ALL, and these data provide a multi-faceted characterization of its molecular features. The datasets described herein, generated with short- and long-read sequencing technologies, can both provide insights into the complex aberrant karyotype of REH, and be used as reference datasets for sequencing data quality assessment or for methods development.
With today's excellent cure rates for Hodgkin lymphoma (HL), the number of long‐term survivors is increasing. This study aims to provide a global assessment of late adverse effects for working‐age HL ...survivors treated with contemporary protocols (combination chemotherapy and limited radiotherapy). From Swedish nationwide registers we identified 1017 HL survivors diagnosed in 2000–2009, aged 18–60 years (median 32) and surviving at least one year post‐diagnosis, and 4031 age‐, sex‐, and calendar‐year‐matched population comparators. Incidence rate ratios (IRR) and 95% confidence intervals (95%CI) for outpatient visits and inpatient bed‐days after the first year up to 14 years post‐diagnosis (through 2013) were estimated across treatment subgroups, considering relapse‐free time and using negative binomial regression. Scheduled outpatient visits for HL were excluded. The rate of outpatient visits was nearly double (IRR = 1.8, 95%CI: 1.6–2.0) that among comparators and higher rates persisted up to 10 years post‐diagnosis. The rate of inpatient bed‐days among relapse‐free survivors was more than three‐fold (IRR = 3.6, 95%CI: 2.7–4.7) that of comparators and the increase persisted up to four years post‐diagnosis. Patients requiring 6‐8 chemotherapy courses had higher rates of outpatient visits (IRR = 1.4, 95%CI: 1.1–1.7) and bed‐days (IRR = 4.7, 95%CI: 2.9–7.8) than patients treated with 2–4 courses + radiotherapy. Previously seldom reported reasons for the excess healthcare use included chest pain, keratitis, asthma, diabetes mellitus, and depression. Contemporary treatment, chemotherapy in particular, was associated with excess healthcare use among HL survivors during the first decade postdiagnosis. The reasons for healthcare visits reflected a wide range of disorders, indicating the need of broad individualized care in addition to specific screening programs.
Advancements in treatments have significantly improved the prognosis for mantle cell lymphoma (MCL), and there is a growing population of survivors with an increased susceptibility to infections. We ...assessed the incidence of infections by clinical characteristics and treatment both before and after MCL diagnosis in Sweden. Patients with a diagnosis of MCL ≥ 18 years between 2007 and 2019 were included, along with up to 10 matched comparators. Infectious disease diagnosis and anti‐infective drug dispensation were identified by the National Patient and the Prescribed Drug Registers, respectively. Patients and comparators were followed from the diagnosis/matching date until death, emigration, or June 30, 2020. Overall, 1559 patients and 15,571 comparators were followed for a median duration of 2.9 and 5 years, respectively. The infection rate among patients was twofold higher, RRadj = 2.14 (2.01–2.27), contrasted to the comparator group. There was a notable rise in infection rates already 4 years before MCL diagnosis, which reached a fourfold increase in the first year after diagnosis and persisted significantly increased for an additional 8 years. Among patients, 69% (n = 1080) experienced at least one infection during the first year of follow‐up. Influenza, pneumonia, other bacterial infections, urinary tract infections, and acute upper respiratory infections were the most frequent. Notably, MCL remained to be the primary leading cause of death among patients (57%, n = 467/817). Infections as the main cause of death were rare (2.6%, n = 21). Our study highlights the importance of thoroughly assessing infectious morbidity when appraising new treatments. Further investigations are warranted to explore strategies for reducing infectious disease burden.
Mantle cell lymphoma (MCL) is a B‐cell malignancy currently considered incurable. Although some patients obtain prolonged remission after first‐line chemoimmunotherapy, many will need several ...treatment lines. Here, we present a nationwide assessment of treatment strategies, time to progression and survival in MCL. All patients diagnosed with MCL 2006–2018 were identified in the Swedish Lymphoma Register. Information on all lines of therapy was extracted from the medical records. Overall and progression‐free survival (OS and PFS) were assessed through August 2021. In total, 1367 patients were included (median age, 71 years) and median follow‐up was 6.8 years. Two hundred and one (15%) were managed initially with watch‐and‐wait, but 1235 (90%) eventually received treatment. The most frequently used first‐line regimens were rituximab‐bendamustine (BR) (n = 368; 30%) and Nordic MCL2 (n = 342; 28%). During follow‐up, 630 patients (46%) experienced relapse/progression and 546 (40%) received second‐line treatment. The most frequently used second‐line regimen was BR (n = 185; 34%) but otherwise a wide variety of second‐line treatments were used. Further, 382 and 228 patients experienced a second or third relapse/progression, respectively. Median PFS after first (PFS‐1), second (PFS‐2), third (PFS‐3), and fourth (PFS‐4) treatment lines was 29.4, 8.9, 4.3, and 2.7 months. Patients with early progression, defined as a PFS‐1 <24 months, had an inferior median OS of 13 versus 37 months in patients with later relapse. For patients treated with frontline BR, however, time to relapse had no impact on later outcome. By use of nationwide population‐based data, we provide important benchmarks for future studies of all treatment lines in MCL.
In follicular lymphoma (FL), progression of disease ≤24 months (POD24) has emerged as an important prognostic marker for overall survival (OS). We aimed to investigate survival more broadly by timing ...of progression and treatment in a national population‐based setting. We identified 948 stage II‐IV indolent FL patients in the Swedish Lymphoma Register diagnosed 2007–2014 who received first‐line systemic therapy, followed through 2020. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated by first POD at any time during follow‐up using Cox regression. OS was predicted by POD using an illness‐death model. During a median follow‐up of 6.1 years (IQR: 3.5–8.4), 414 patients experienced POD (44%), of which 270 (65%) occurred ≤24 months. POD was represented by a transformation in 15% of cases. Compared to progression‐free patients, POD increased all‐cause mortality across treatments, but less so among patients treated with rituximab(R)‐single (HR = 4.54, 95% CI: 2.76‐7.47) than R‐chemotherapy (HR = 8.17, 95% CI: 6.09‐10.94). The effect of POD was similar following R‐CHOP (HR = 8.97, 95% CI: 6.14‐13.10) and BR (HR = 10.29, 95% CI: 5.60‐18.91). The negative impact of POD on survival remained for progressions up to 5 years after R‐chemotherapy, but was restricted to 2 years after R‐single. After R‐chemotherapy, the 5‐year OS conditional on POD occurring at 12, 24, and 60 months was 34%, 46%, and 57% respectively, versus 78%, 82%, and 83% if progression‐free. To conclude, POD before but also beyond 24 months is associated with worse survival, illustrating the need for individualized management for optimal care of FL patients.
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