57 research outputs found

    Cardiovascular diseases after high-dose chemotherapy and autologous stem cell transplant for lymphoma: A Danish population-based study

    Get PDF
    Cardiovascular diseases, especially congestive heart failure (CHF), are known complications of anthracyclines, but the risk for patients undergoing high-dose chemotherapy and autologous stem cell transplant (HDT-ASCT) is not well established. With T-cell therapies emerging as alternatives, studies of long-term complications after HDT-ASCT are warranted. Danish patients treated with HDT-ASCT for aggressive lymphoma between 2001 and 2017 were matched 1:5 on sex, birth year and Charlson comorbidity score to the general population. Events were captured using nationwide registers. A total of 787 patients treated with HDT-ASCT were identified. Median follow-up was 7.6 years. The risk of CHF was significantly increased in the HDT-ASCT population compared to matched comparators with an adjusted hazard ratio (HR) of 5.5 (3.8–8.1). The 10-year cumulative incidence of CHF was 8.0% versus 2.0% (p &lt; 0.001). Male sex, ≥2 lines of therapy, hypertension and cumulative anthracycline dose (≥300 mg/m 2) were risk factors for CHF. In a separate cohort of 4089 lymphoma patients, HDT-ASCT was also significantly associated with increased risk of CHF (adjusted HR of 2.6 [1.8–3.8]) when analysed as a time-dependent exposure. HDT-ASCT also increased the risk of other cardiac diseases. These findings are applicable for the benefit/risk assessment of HDT-ASCT versus novel therapies.</p

    Chronic fatigue in long-term survivors of Hodgkin’s lymphoma after contemporary risk-adapted treatment

    No full text
    Chronic fatigue (CF), substantial fatigue for ≥ six months, can manifest as a late effect (LE) after cancer treatment, and may affect several aspects of life. In a Norwegian cohort of Hodgkin’s lymphoma survivors (HLS), more than a decade after contemporary risk-adapted treatment regimens with limited use of radiotherapy (RT), we assessed: (1) Prevalence of, (2) factors associated with (3) and implications of CF on socioeconomic status (SES) and work ability (WA). HLS treated between 1997–2006, aged 8–49 years at diagnosis, were invited to participate in a population-based cross-sectional study on late effects in 2018–2019. In a mailed questionnaire, HLS responded to a fatigue questionnaire (FQ), work ability score (WAS) and short-form health survey (SF-36). Disease- and treatment data were extracted from hospital records. Factors associated with CF were identified by uni- and multivariate analysis. To study the implications of CF on SES and WA, a multinomial regression analysis was performed. Invitations were extended to 518 HLS and 298 (58%) responded to FQ, of whom 42% had CF with mean (standard deviation [SD]) physical- and mental fatigue scores of 10.2 (4.3) and 5.5 (2.1) respectively. Median age at survey was 45 years, 47% were females. In multivariate analysis female sex (p = 0.03), lower education (p = 0.03), body mass index ≥30 kg/m2 (p = 0.04), and an increasing number of comorbidities (p = 0.01) were associated with CF. No association with disease stage, chemotherapy or RT was found. CF was associated with poorer WAS scores at survey (p p = 0.03), and receiving disability pension (p = 0.003). After risk-adapted treatment, CF is still a frequent LE among long-term HLS, without apparent association with disease or treatment-related parameters. CF is associated with reduced WA and SES. As no apparent risk reduction is seen with contemporary treatment, further studies should emphasize etiological factors of CF and treatment to alleviate this common LE.</p

    Obstructive and restrictive pulmonary dysfunction in long-term lymphoma survivors after high-dose therapy with autologous stem cell transplantation

    No full text
    <p><b>Background:</b> Obstructive and restrictive dysfunction in long-term lymphoma survivors (LSs) after high-dose therapy with autologous stem-cell transplantation (HDT-ASCT) has not been addressed systematically previously.</p> <p><b>Material and methods:</b> LSs treated in Norway 1987–2008 with HDT-ASCT who performed spirometry, measurement of static lung volumes and echocardiography 2012–2014 at either Oslo or St. Olavs University Hospitals was eligible. Smoking data were recorded by questionnaire. Treatment data were collected from medical records or hospital databases. Factors associated with obstructive and restrictive impairments (dichotomous outcomes) were examined by Poisson regression. Linear regression with the margins post-estimation command was used to derive adjusted mean values of forced expiratory volume in 1 s (FEV<sub>1</sub>). We used the normative reference data recommended by the European Respiratory Society for calculating percent predicted values.</p> <p><b>Results:</b> A total of 226 LSs were studied, of whom 11.5 and 5.8% had obstructive and restrictive impairment, respectively. For women and men, mean FEV<sub>1</sub> was 2.31 and 3.34 l corresponding to 11.4%- and 11.1%-points below that predicted from norms, respectively. In multivariable regression analyses, cumulative doxorubicin dose (400–775 mg/m<sup>2</sup>) and current smoking were associated with increased risk of obstructive impairment, and chest RT (>13–66 Gy) was associated with increased risk of restrictive impairment. Currently smoking LSs within the highest doxorubicin category (400–775 mg/m<sup>2</sup>), had the lowest adjusted mean FEV<sub>1</sub>.</p> <p><b>Conclusions:</b> Despite intensive cancer treatment, our analysis showed modest reductions in obstructive parameters among long-term LSs after HDT-ASCT compared to normative reference data. To limit obstructive impairments in LSs after HDT-ASCT, we suggest that targeted smoking-cessation advice is directed towards patients who have received high cumulative doses of doxorubicin.</p

    A Gene Panel, Including <i>LRP12</i>, Is Frequently Hypermethylated in Major Types of B-Cell Lymphoma

    No full text
    <div><p>Epigenetic modifications and DNA methylation in particular, have been recognized as important mechanisms to alter gene expression in malignant cells. Here, we identified candidate genes which were upregulated after an epigenetic treatment of B-cell lymphoma cell lines (Burkitt's lymphoma, BL; Follicular lymphoma, FL; Diffuse large B-cell lymphoma, DLBCL activated B-cell like, ABC; and germinal center like, GCB) and simultaneously expressed at low levels in samples from lymphoma patients. Qualitative methylation analysis of 24 candidate genes in cell lines revealed five methylated genes (<i>BMP7, BMPER</i>, <i>CDH1</i>, <i>DUSP4</i> and <i>LRP12</i>), which were further subjected to quantitative methylation analysis in clinical samples from 59 lymphoma patients (BL, FL, DLBCL ABC and GCB; and primary mediastinal B-cell lymphoma, PMBL). The genes <i>LRP12</i> and <i>CDH1</i> showed the highest methylation frequencies (94% and 92%, respectively). <i>BMPER</i> (58%), <i>DUSP4</i> (32%) and <i>BMP7</i> (22%), were also frequently methylated in patient samples. Importantly, all gene promoters were unmethylated in various control samples (CD19+ peripheral blood B cells, peripheral blood mononuclear cells and tonsils) as well as in follicular hyperplasia samples, underscoring a high specificity. The combination of <i>LRP12</i> and <i>CDH1</i> methylation could successfully discriminate between the vast majority of the lymphoma and control samples, emphasized by receiver operating characteristic analysis with a c-statistic of 0.999. These two genes represent promising epigenetic markers which may be suitable for monitoring of B-cell lymphoma.</p></div

    Identification of Highly Methylated Genes across Various Types of B-Cell Non-Hodgkin Lymphoma

    No full text
    <div><p>Epigenetic alterations of gene expression are important in the development of cancer. In this study, we identified genes which are epigenetically altered in major lymphoma types. We used DNA microarray technology to assess changes in gene expression after treatment of 11 lymphoma cell lines with epigenetic drugs. We identified 233 genes with upregulated expression in treated cell lines and with downregulated expression in B-cell lymphoma patient samples (n = 480) when compared to normal B cells (n = 5). The top 30 genes were further analyzed by methylation specific PCR (MSP) in 18 lymphoma cell lines. Seven of the genes were methylated in more than 70% of the cell lines and were further subjected to quantitative MSP in 37 B-cell lymphoma patient samples (diffuse large B-cell lymphoma (activated B-cell like and germinal center B-cell like subtypes), follicular lymphoma and Burkitt`s lymphoma) and normal B lymphocytes from 10 healthy donors. The promoters of <i>DSP</i>, <i>FZD8</i>, <i>KCNH2,</i> and <i>PPP1R14A</i> were methylated in 28%, 67%, 22%, and 78% of the 36 tumor samples, respectively, but not in control samples. Validation using a second series of healthy donor controls (n = 42; normal B cells, peripheral blood mononuclear cells, bone marrow, tonsils and follicular hyperplasia) and fresh-frozen lymphoma biopsies (n = 25), confirmed the results. The DNA methylation biomarker panel consisting of <i>DSP</i>, <i>FZD8</i>, <i>KCNH2,</i> and <i>PPP1R14A</i> was positive in 89% (54/61) of all lymphomas. Receiver operating characteristic analysis to determine the discriminative power between lymphoma and healthy control samples showed a c-statistic of 0.96, indicating a possible role for the biomarker panel in monitoring of lymphoma patients.</p></div
    • …
    corecore