Harald Holte

Oslo University Hospital, Kristiania (historical), Oslo, Norway

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Publications (178)1023.59 Total impact

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    ABSTRACT: Cancer treatment may lead to hormonal dysfunction. Therefore, we assessed the prevalence of dysfunction in four hormonal axes among long-term cancer survivors who received radiotherapy to the head and neck region and analyzed associations between hormonal status and clinical variables. We included 140 cancer survivors who received radiotherapy to the head and neck region, either locally or through total body irradiation after a diagnosis of lymphoma, plasmacytoma/multiple myeloma, or carcinoma of the epipharynx. Radiation doses to the pituitary gland and thyroid gland were estimated, and blood samples were collected to analyze hormonal levels. At a median of 16 years after their cancer diagnosis, 46 % of cancer survivors showed dysfunction in one hormonal axis, 24 % had dysfunction in two axes, and 3 % had dysfunction in three axes. Twenty cancer survivors (14 %) had hormone levels consistent with pituitary dysfunction. Cancer survivors who had received an estimated 30 Gray (Gy) or more to the pituitary gland had an increased risk for pituitary dysfunction in one of the hormonal axes (odds ratio [OR] 3.16, confidence interval [CI] 1.02-9.87, p = 0.047) and for growth hormone dysfunction alone (OR 2.96, CI 1.02-8.55, p = 0.045). Abnormal hormone values are frequent after radiotherapy to the head and neck region. Screening for hormonal dysfunction during follow-up might be indicated.
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    ABSTRACT: Abstract Patients with advanced CD20+ indolent lymphoma, requiring therapy, were randomized to rituximab (4 weekly infusions of 375 mg/m2) or to rituximab combined with 5 weeks of IFN-α2a (3-4.5 MIU daily) as priming. Responding patients were eligible for a second cycle with the same allocated treatment. In total, 156 patients were randomized to rituximab and 157 to rituximab + IFN-α2a. In the intention-to treat (ITT) population, 244 patients (78%) responded to cycle 1. After a second cycle the CR/CRu rate was 41% with the combination vs 24 % with monotherapy (p=0.005).The median time to treatment failure (primary endpoint) in ITT patients was 28 vs 21.5 months, respectively (p=0.302). After a long median follow-up (61 months), 33% (42% of patients responding to cycle 1) were still failure-free with an overall survival rate of 88% and with no difference between the treatment groups. The trial was registered at ClinicalTrials.gov Identifier: NCT01609010.
    Leukemia and Lymphoma 02/2015; DOI:10.3109/10428194.2015.1014363 · 2.61 Impact Factor
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    ABSTRACT: - Copyright © 2015, Ferrata Storti Foundation.
    Haematologica 02/2015; DOI:10.3324/haematol.2014.119214 · 5.94 Impact Factor
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    ABSTRACT: The prognostic impact of tumor microenvironment has not been systematically assessed in diffuse large B-cell lymphoma. We analyzed mRNA and antigen expression of monocytes, macrophages, lymphocytes, dendritic and natural killer cells in pretreatment tumor samples of high-risk diffuse large B-cell lymphoma patients using gene expression microarray and immunohistochemistry. The patients were treated in a Nordic phase II study with dose-dense chemoimmunotherapy and central nervous system prophylaxis. Of the studied markers for non-malignant inflammatory cells, CD68 expression and CD68+ macrophage counts correlated with favorable outcome. Five-year progression free survival rates were 83% and 43% for the patients with high and low CD68 mRNA levels (p=0.007), and overall survival 83% and 64%, respectively (p=ns). Likewise, the patients with high CD68+macrophage counts displayed a better five-year progression free survival (74% vs. 40%, p=0.003) and overall survival (90% vs. 60%, p=0.009) than the patients with low macrophage counts. Low CD68+ macrophage content retained its prognostic impact on overall survival with age-adjusted international prognostic index (RR=5.0 (95% CI 1.024-19.088), p=0.017). The findings were validated in three independent cohorts of chemoimmunotherapy treated patients. In contrast, in patients treated with chemotherapy, high CD68+ macrophage content was associated with poor progression free survival (40% vs. 72%, p=0.021) and overall survival (39% vs. 72%, p=0.015). Together, the data suggest that macrophages exhibit a dual treatment specific role in diffuse large B-cell lymphoma. For the patients treated with chemoimmunotherapy, high pretreatment CD68 mRNA levels and CD68+ macrophage numbers predict favorable outcome. ClinicalTrials.gov number NCT0150298.
    Haematologica 11/2014; DOI:10.3324/haematol.2014.113472 · 5.94 Impact Factor
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    ABSTRACT: AimsManual counting of the fraction of Ki-67 positive cells (the Ki-67 index) in 1000 tumor cells is considered the “gold standard” to predict prognosis in mantle cell lymphoma (MCL). This time-consuming method is replaced by the faster, but less accurate semiquantitative estimation in routine practice. The aim of this study was to investigate the use of computerized image analysis software for scoring of Ki-67 in MCL.Methods And ResultsWe developed an automated method for determining the Ki-67 index by computerized image analysis and tested it using a cohort of 62 MCL patients. The data were compared to Ki-67 scores obtained by semiquantitative estimation and image based manual counting. When using the Ki-67 index as a continuous parameter, both image based manual counting and computerized image analysis were inversely related to survival (p = 0.020 and p = 0.025, respectively). Ki-67 index obtained by semiquantitative estimation was not significantly associated with survival (p = 0.093). The results were validated in a second patient cohort with similar results.Conclusion Computerized image analysis of the Ki-67 index in MCL is an attractive alternative to semiquantitative estimation and can easily be introduced in a routine diagnostic setting for risk stratification in MCL.This article is protected by copyright. All rights reserved.
    Histopathology 11/2014; DOI:10.1111/his.12624 · 3.30 Impact Factor
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    ABSTRACT: ABSTRACT We evaluated the predictive value of I-PET after one course of chemoimmunotherapy in patients with newly diagnosed DLBCL. 112 DLBCL patients were enrolled. All patients had PET/CT scans performed after one course of chemotherapy (PET-1). I-PET scans were categorized according to International harmonization project criteria (IHP) and to Deauville 5 point scale (D 5PS) with scores 1-3 considered negative (D 5PS>3) and D 5PS with scores 1-4 considered negative (D5PS=5). Ratios of tumorSUVmax to liverSUVmax were also analyzed. We found no difference in progression-free survivals (PFS) between PET-negative and PET-positive patients according to IHP and D 5PS>3. The 2-year PFS using D 5PS=5 was 50.9% in the PET-positive group and 84.8% in the PET-negative group (p=0.002). A tumor/liver SUVmax cut-off of 3.1 to distinguish a D 5PS scores of 4 and 5 provided the best prognostic value. PET after one course of chemotherapy was not able to safely discriminate PET positive and PET negative patients in different prognostic groups.
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    ABSTRACT: Advanced stage follicular lymphoma (FL) is incurable by conventional therapies. In the present pilot clinical trial we explored the efficacy and immunogenicity of a novel in situ immunotherapeutic strategy. Fourteen patients with untreated or relapsed stage III/IV FL were included and received local radiotherapy to solitary lymphoma nodes and intra-nodal injections of low-dose rituximab (5 mg), immature autologous dendritic cells and GM-CSF at the same site. The treatment was repeated three times targeting different lymphoma nodes. Primary end points were clinical responses and induction of systemic immunity. Five out of fourteen patients (36%) displayed objective clinical responses, including one patient with cutaneous FL who showed regression of skin lesions. Two of the patients had durable complete remissions. Notably, the magnitude of vaccination-induced systemic CD8 T cell-mediated responses correlated closely with reduction in total tumor area (r=0.71, p=0.006) and immune responders showed prolonged time to next treatment. Clinical responders did not have a lower tumor burden than non-responders pre-treatment, suggesting that the T cells could eliminate large tumor masses once immune responses were induced. In conclusion, the combined use of three treatment modalities, and in situ administration in single lymphoma nodes, mediated systemic T-cell immunity accompanied by regression of disseminated FL. The study was registered at www.clinicaltrials.gov as #NCT01926639.
    Blood 10/2014; DOI:10.1182/blood-2014-07-592162 · 9.78 Impact Factor
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    ABSTRACT: Abstract Translocations affecting both MYC and BCL2 are associated with poor prognosis in diffuse large B-cell lymphomas. We have examined genetic aberrations combined with analyses of protein expression of respective gene products. Fluorescence in situ hybridization (FISH) for translocations of BCL2 and MYC and del17p13 was performed. Immunohistochemistry analyses included BCL2, -MYC and TP53 protein expression. Sixty-seven patients with high risk DLBCL participating in a prospective multicenter study were included. Six patients with simultaneous translocations of BCL2 and MYC had impaired overall (OS) (p=0.017) and progression-free survival (PFS) (p=0.009). Six patients with high co-expression of MYC and BCL2 proteins also had impaired OS (p=0.004) and PFS (p=0.002). Combining these groups identified nine patients with impaired OS (p=0.004) and PFS (p=0.005). Sixteen patients had double-hit translocation or protein expression and/or del17p13 and/or high TP53. This combined endpoint was associated with impaired OS (p=0.008) and PFS (p=0.036), and identified 70% of all deaths.
    Leukemia and Lymphoma 10/2014; DOI:10.3109/10428194.2014.970550 · 2.61 Impact Factor
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    ABSTRACT: 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 (BMP7, BMPER, CDH1, DUSP4 and LRP12), 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 LRP12 and CDH1 showed the highest methylation frequencies (94% and 92%, respectively). BMPER (58%), DUSP4 (32%) and BMP7 (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 LRP12 and CDH1 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.
    PLoS ONE 09/2014; 9(9):e104249. DOI:10.1371/journal.pone.0104249 · 3.53 Impact Factor
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    ABSTRACT: Purpose The purpose was to assess gonadal hormones in male survivors after high dose chemotherapy with autologous stem cell transplantation (HDT) for lymphoma. Methods All male survivors aged ≥ 18 years at treatment with HDT for lymphoma in Norway from 1987-2008 were eligible for this cross-sectional survey performed in 2012/2013. Morning blood samples were drawn for assessment of testosterone, luteinizing hormone (LH), follicle stimulating hormone (FSH) and sex hormone binding globulin (SHBG) in 161 participants. Free testosterone index (fTi) was calculated as testosterone/SHBG x10. Age adjusted reference levels were used for categorization of hormone levels into: A: normal, B: elevated FSH only and C: low fTi and/or elevated LH, with or without elevated FSH. Treatment period was divided into: 1987-1995, 1996-2002 and 2003-2008. HDT was administered as high dose cyclophosphamide/total body irradiation in the first period and as chemotherapy (BEAM) in the latter two periods. Multinomial regression analyses were performed with p<0.05 considered statistically significant. Results Median age at HDT was 47 years (19-67), median age at survey 54 years (25-76) and median observation time from HDT to survey was 7.8 years (3-22). Twenty-nine (18%) had normal gonadal hormones, 70 (44%) had elevated FSH only and 62 (39%) had low fTi and/or elevated LH with 8 of these currently being on testosterone substitution. Compared to treatment period 2003-2008, treatment period 1987-1995 was significantly associated with increased risk for low fTi/elevated LH (OR:9.7, 95%CI: 1.2-80.0), whereas treatment in 1996-2002 reduced the risk for elevated FSH only (OR:0.36, 95%CI:0.14-0.95). Infradiaphragmatic radiotherapy was significantly associated with increased risk of having low fTi/elevated LH (OR:3.0, 95%CI: 1.1-8.3). Conclusions Male gonadal hormone dysfunction is prevalent after HDT for lymphoma especially after infradiaphragmatic radiotherapy. Awareness of this is important as hypogonadism might be associated with reduced energy levels, sexual dysfunction and osteoporosis.
    The 12th Acta Oncologica Symposium, European Cancer Rehabilitation & Survivorship Symposium, Copenhagen, Denmark; 09/2014
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    ABSTRACT: Purpose Investigate survival after HDT for Hodgkin’s lymphoma (HL), and analyse cause of death (COD) and incidence of second cancers (SC). Methods All patients ≥18 years treated with HDT for relapsed/refractory HL in Norway 1987-2008 were included (n=150). Data on COD from Statistics Norway and on second cancers from Cancer Registry of Norway were linked with clinical data. Observation time was estimated from HDT to death or cut-off (December 31 2011). Crude cumulative probabilities for survival were calculated by Kaplan-Meier method, and groups compared with log-rank tests. Cox regression was used for multivariate analysis. Conditional survival was calculated using the multiplicative law of probability. Results With median observation time from HDT of 9.7 years (0-22.25), a total of 52 deaths (35%) were observed. The 5-, 10- and 15-year overall survival (OS) was 73% (95%CI 65%-80%), 65% (95%CI 57%-73%) and 60% (95%CI 50%-70%). The 5-year OS conditioned on having survived 2, 5 and 10 years from diagnosis was 80%, 89% and 93%. Earlier treatment periods (1987-1995 vs 1996-2002 vs 2003-2008) (p=0,01) and relapse after HDT (p<0.001) were significantly associated with poorer survival in both univariate and multivariate analysis. Forty (77%) died from HL, 1 from NHL, 3 from leukaemia, 2 from heart disease and 6 from other causes. HL-deaths occurred after median 1.8 years (0-13) and non-HL deaths 4.2 years (0-13). SC was observed in 8 patients at median 5.25 years (1.25-13.25) after HDT (NHL (n=4), leukaemia (n=2) and solid tumours (n=2)). Conclusions Survival after HDT for HL in Norway is good. The OS probability rapidly increases after surviving few years, and approach 95% within 8 years. The incidence of SC was only 5%. Diminished use of alkylating agents and radiotherapy during the last two decades may have improved long term survival, but longer follow up is needed for firm conclusions.
    The 12th Acta Oncologica Symposium, European Cancer Rehabilitation & Survivorship Symposium, Copenhagen, Denmark; 09/2014
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    ABSTRACT: Background. Few studies have explored fatigue in different groups of lymphoma survivors and the association with hormonal dysfunctions. The aims were to analyze associations between fatigue and thyroid and gonadal function in male lymphoma survivors. In addition, the impact of chronic fatigue on work situation and daily functioning were explored. Patients and methods. This cross-sectional study included male lymphoma survivors diagnosed in 1980–2002, aged ≤ 50 years at diagnosis and > 18 years at survey in 2007. The participants (n = 233, median age at survey: 48 years, median observation time: 15 years) completed questionnaires assessing levels of fatigue, chronic fatigue (duration ≥ 6 months), mental distress, daily functioning and work situation. Levels of thyroid and gonadal hormones were assessed. The participants were grouped according to diagnosis: Hodgkin lymphoma (HL, n = 131), aggressive/very aggressive non-Hodgkin lymphoma (NHL) (n = 67) and indolent NHL (n = 35). Thyroid hormones were categorized as normal (n = 174) or latent hypothyroidism (elevated thyroid stimulating hormone, n = 59). Gonadal hormones were categorized as normal (n = 111), elevated follicle stimulating hormone only (n = 45), primary (n = 35) or secondary hypogonadism (n = 42). Uni- and multivariate regression analyses were performed. A p value < 0.05 indicated the level of significance. Results. The survivors of HL and aggressive/very aggressive NHL had similar fatigue levels and similar prevalence of chronic fatigue (HL: 31%, aggressive/very aggressive; NHL: 27%). Survivors of indolent NHL had lower fatigue levels and prevalence of chronic fatigue (11%). Latent hypothyroidism was associated with increased fatigue levels (p = 0.042). Gonadal function was not associated with levels of fatigue or chronic fatigue. Mental distress was associated with increasing fatigue levels and chronic fatigue (p < 0.001). We found negative associations between chronic fatigue, daily functioning and work status. Conclusions. Fatigued lymphoma survivors should be investigated for thyroid function. The negative impact of chronic fatigue on daily functioning and work status emphasizes the importance of maintaining the effort in understanding the mechanisms behind fatigue.
    Acta Oncologica 08/2014; DOI:10.3109/0284186X.2014.948057 · 3.71 Impact Factor
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    ABSTRACT: Introduction: High dose chemotherapy with autologous stem cell support (HDT) has been used in the treatment of lymphomas for specific indications in Norway since 1987. No systematic follow-up program for long-term HDT survivors has been set up in Norway as of today. In this national multi-center follow-up study we investigate a broad spectrum of late effects after HDT for lymphoma. Methods: All lymphoma patients treated with HDT in Norway from 1987-2008, aged ≥18 years at HDT were eligible. Survivors were invited to complete a questionnaire and undergo a two-day medical examination at the out-patient clinic at one of the four University hospitals where they had been treated. The examinations included a structured interview concerning late effects, a clinical examination, chest X-ray, blood samples, bone mineral density, echocardiography, spirometry, exercise test and cognitive function tests. Registry data were obtained from The Cancer Registry and Statistics Norway. Results: A total of 728 adult lymphoma patients had received HDT by the end of 2008. By Jan 1 2012, 407 were alive. A total of 399 survivors were contacted, 311 (78%) completed the questionnaire and 285 (71%) attended the clinical examinations. Survivors with clinical findings were referred to further evaluation, treatment or appropriate counselling when needed. Each patient and their GP received a written summary with advice for further follow-up. Conclusions/Implications: By this project all eligible HDT survivors were offered a comprehensive medical follow- up. The combination of patient-reported outcomes, treatment data, clinical examinations including blood sampling and registry-based data in a national cohort of HDT survivors will increase all involved clinician's and researcher's knowledge about late effects after this highly intensive treatment. The multidisciplinary approach with participation of several specialities in all health regions will increase the understanding of the late effects after HDT, and enhance collaboration between different specialities and health regions/hospitals.
    7th Biennial Cancer Survivorship Research Conference, Atalanta; 06/2014
  • 7th Biennial Cancer Survivorship Research Conference, Atlanta; 06/2014
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    ABSTRACT: Despite improved survival for the patients with diffuse large B-cell lymphoma (DLBCL), the prognosis after relapse is poor. The aim was to identify molecular events that contribute to relapse and treatment resistance in DLBCL. We analysed 51 prospectively collected pretreatment tumour samples from clinically high risk patients treated in a Nordic phase II study with dose-dense chemoimmunotherapy and central nervous system prophylaxis with high resolution array comparative genomic hybridization (aCGH) and gene expression microarrays. Major finding was validated at the protein level immunohistochemically in a trial specific tissue microarray series of 70, and in an independent validation series of 146 patients. We identified 31 genes whose expression changes were strongly associated with copy number aberrations. In addition, gains of chromosomes 2p15 and 18q12.2 were associated with unfavourable survival. The 2p15 aberration harboured COMMD1 gene, whose expression had a significant adverse prognostic impact on survival. Immunohistochemical analysis of COMMD1 expression in two series confirmed the association of COMMD1 expression with poor prognosis. COMMD1 is a potential novel prognostic factor in DLBCLs. The results highlight the value of integrated comprehensive analysis to identify prognostic markers and genetic driver events not previously implicated in DLBCL. ClinicalTrials.gov NCT01502982.
    PLoS ONE 03/2014; 9(3):e91031. DOI:10.1371/journal.pone.0091031 · 3.53 Impact Factor
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    ABSTRACT: 18F fluoro-deoxyglucose (FDG) positron emission tomography / computed tomography (PET/CT) is a well-recognized diagnostic tool used for staging and monitoring of therapy response for lymphomas. During the past decade diffusion-weighted (DW) magnetic resonance imaging (MRI) is increasingly being included in the assessment of tumor response for various cancers. To compare the change in maximum standardized uptake value (ΔSUVmax) from FDG PET/CT with the change in apparent diffusion coefficient (ΔADC) from DW MRI after initiation of the first cycle of chemotherapy in patients with Hodgkin's lymphoma (HL) and in patients with diffuse large B-cell lymphoma (DLBCL). Twenty-seven consecutive patients with histologically proven lymphoma and lymphomatous lymph nodes (LLN) of the neck (19 with HL, 8 with DLBCL) underwent FDG PET/CT and MRI of the neck before and after initiation of the first cycle of chemotherapy. The mean time interval from initiation of chemotherapy to imaging was 19 days and 2 days for FDG PET/CT and MRI, respectively. For each patient ΔSUVmax, ΔADC, and change in volume of the same LLN were compared. There was a significant mean decrease of SUVmax by 70%, but no significant change in ADC. There was no significant reduction in LLN volume. There was no significant correlation between ΔSUVmax and ΔADC. Thus, our data do not support that FDG PET/CT can be replaced by early DW MRI for response evaluation in lymphoma patients.
    Acta Radiologica 02/2014; 56(2). DOI:10.1177/0284185114526087 · 1.35 Impact Factor
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    ABSTRACT: Transformation of follicular lymphoma (FL) to a more aggressive disease is associated with rapid progression and death. Existing molecular markers for transformation are few and their clinical impact is limited. Here, we report on a whole-genome study of DNA copy numbers and gene expression profiles in serial FL biopsies. We identified 698 genes with high correlation between gene expression and copy number and the molecular network most enriched for these cis-associated genes. This network includes 14 cis-associated genes directly related to the NFκB pathway. For each of these 14 genes, the correlated NFκB target genes were identified and corresponding expression scores defined. The scores for six of the cis-associated NFκB pathway genes (BTK, IGBP1, IRAK1, ROCK1, TMED7-TICAM2 and TRIM37) were significantly associated with transformation. The results suggest that genes regulating B-cell survival and activation are involved in transformation of FL.
    Blood 02/2014; 123(7):1051-1054. DOI:10.1182/blood-2013-07-512392. · 9.78 Impact Factor
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    ABSTRACT: Abstract High dose chemotherapy with autologous stem cell transplantation (HD-ASCT) is a recommended procedure for patients with transformed indolent B-cell lymphoma from the pre-rituximab era. In this retrospective single-center study, we present our experience with HD-ASCT in patients with histologically verified transformed indolent B-cell lymphomas in the rituximab era. Forty-two patients were included, of whom 28 patients with chemosensitive disease proceeded to HD-ASCT. Twenty patients (71%) achieved complete remission (CR) and five (18%) partial remission (PR) after HD-ASCT. With a median observation time of 49 months for the survivors, the median progression-free survival (PFS) and overall survival (OS) for HD-ASCT patients were 39 months and 57 months, respectively. The patients who were rituximab-naïve at transformation had a significantly better OS compared to the patients previously treated with rituximab, both in the whole patient cohort and among the HD-ASCT-treated patients (P = 0.036 and P = 0.039 respectively). Furthermore, male sex influenced survival negatively whereas time from diagnosis to transformation was positively associated with survival, both with borderline significance in the HD-ASCT-treated patients. In conclusion, HD-ASCT remains an effective treatment for transformed indolent lymphomas in the rituximab era.
    Leukemia & lymphoma 01/2014; 55(10). DOI:10.3109/10428194.2013.871632 · 2.61 Impact Factor
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    ABSTRACT: Purpose: Lymphoma survivors (LS) have increased cardiovascular disease burden, because of cardiotoxic treatment, in particular anthracyclines (AC) and radiotherapy (RT) involving the heart. Our aim in the present study was to assess RV systolic function after RT in this patient group. Methods: All LS treated with high dose chemotherapy with autologous stem cell transplantation (HDT) in Norway in the period 1987–2008, aged ≥18yr at time of HDT were invited to a medical examination including echocardiography. This report includes 186 LS (66% men) examined at our universitary hospital. All had received AC and 78 had additional radiotherapy involving the heart. Patients were categorized into three groups according to treatment: AC (n=108, age 58yr ± 12yr, 11yr ± 5yr since primary treatment), AC-MRT (mediastinal radiotherapy, median dose 31Gy, range 19-41Gy, n=39, age 47yr ± 12yr, 14yr ± 6yr since primary treatment) and AC-TBI (total body irradiation, 13 Gy, n=39, age 56yr ± 10yr, 22yr ± 3yr since primary treatment). Conventional echocardiograms were obtained by Vivid 7 or E9 (GE Vingmed, Norway). RV global longitudinal strain (GLS, six segments) and RV-free wall GLS (three segments) by two-dimensional speckle tracking, and fractional area change (FAC) of the RV were all measured from the apical four chamber view. Analysis for differences between groups according to treatment were done by One-Way ANOVA. Results: RV systolic function was significantly impaired in LS receiving AC + RT involving the heart compared with LS treated with AC, as judged by most parameters of RV systolic function (table 1). The treatmentgroups had comparable body mass index, p=0.96. Conclusion: RV systolic function is impaired when RT involving the heart is added to AC in LS.
    European Heart Journal (2014), Barcelona; 01/2014
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    ABSTRACT: Genes with altered DNA methylation can be used as biomarkers for cancer detection and assessment of prognosis. Here we analyzed the methylation status of a colorectal cancer biomarker panel (CNRIP1, FBN1, INA, MAL, SNCA, and SPG20) in 97 cancer cell lines, derived from 17 different cancer types. Interestingly, the genes were frequently methylated also in hematological cancer types and were therefore subjected to analyses in primary tumor samples from the major types of non-Hodgkin lymphomas (NHL) and in healthy controls. In total, the genes CNRIP1, FBN1, INA, MAL, SNCA, and SPG20 were methylated in 53%, 23%, 52%, 69%, 97%, and 92% of the tumor samples, respectively, and were unmethylated in all healthy controls. With the exception of a single tumor sample, a correct prediction of lymphoma or normal sample was made in a blinded analysis of the validation series using a combination of SNCA and SPG20. The combined ROC-curve analysis of these genes resulted in an area under the curve of 0.999 (P = 4.2 × 10(-18)), and a sensitivity and specificity of 98% and 100%, respectively, across the test and validation series. Interestingly, the promoter methylation of CNRIP1 was associated with decreased overall survival in DLBCL (P = 0.03). In conclusion, our results demonstrate that SNCA and SPG20 methylation might be suitable for early detection and monitoring of NHL. Furthermore, CNRIP1 could potentially be used as a prognostic factor in DLBCL.
    Epigenetics: official journal of the DNA Methylation Society 12/2013; 9(3). DOI:10.4161/epi.27554 · 5.11 Impact Factor

Publication Stats

8k Citations
1,023.59 Total Impact Points

Institutions

  • 1996–2015
    • Oslo University Hospital
      • • Department of Oncology
      • • Institute for Cancer Research
      Kristiania (historical), Oslo, Norway
  • 1999–2014
    • University of Oslo
      • • Centre for Cancer Biomedicine
      • • Department of Oncology
      Kristiania (historical), Oslo, Norway
  • 2002–2007
    • National Institutes of Health
      • • Center for Cancer Research
      • • Branch of Metabolism
      Bethesda, MD, United States
  • 2004
    • Northern Inyo Hospital
      BIH, California, United States
  • 1994–2002
    • Det Norske Veritas
      Kristiania (historical), Oslo County, Norway
  • 1990–1998
    • Institutt for samfunnsforskning, Oslo
      Kristiania (historical), Oslo County, Norway
  • 1987–1993
    • Norwegian Cancer Society
      Kristiania (historical), Oslo County, Norway