| 1. |
- Andreasson, Ulrika, et al.
(författare)
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Identification of molecular targets associated with transformed diffuse large B cell lymphoma using highly purified tumor cells
- 2009
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Ingår i: American Journal of Hematology. - : Wiley. - 0361-8609 .- 1096-8652. ; 84:12, s. 803-808
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Tidskriftsartikel (refereegranskat)abstract
- Follicular lymphoma (FL) frequently transforms into the more aggressive diffuse large B cell lymphoma (DLBCL-tr), but no protein biomarkers have been identified for predictive or early diagnosis. Gene expression analyses have identified genes changing on transformation but have failed to be reproducible in different studies, reflecting the heterogeneity within the tumor tissue and between tumor samples. Gene expression analyses on Affymetrix Human Genome U133 Plus 2.0 arrays were performed, using flow cytometry sorted tumor cells derived from FL and transformed DLBCL. To identify molecular targets associated with the transformation, subsequent immunohistochemistry (IHC) analyses of the corresponding proteins were performed. Using highly purified cells, this study identified 163 genes, which were significantly deregulated during the transformation in a majority of cases. Among the upregulated transcripts, 13 genes were selected for validation using IHC, based on the availability of commercial antibodies, and galectin-3 and NEK2 proteins specifically identify DLBCL-tr, when compared with FL. We demonstrate that by purifying tumor cells through cell sorting, thereby reducing the heterogeneity due to infiltrating cells, it was possible to identify distinct differences between tumor entities rather than variations due to cellular composition. Galectin-3 and NEK2 both identified a subgroup of DLBCL-tr, and the function of these protein markers also suggests a biological role in the transformation process.
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| 2. |
- Andreasson, Ulrika, et al.
(författare)
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Identification of uniquely expressed transcription factors in highly purified B-cell lymphoma samples.
- 2010
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Ingår i: American Journal of Hematology. - : Wiley. - 0361-8609 .- 1096-8652. ; 85:6, s. 418-425
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Tidskriftsartikel (refereegranskat)abstract
- Transcription factors (TFs) are critical for B-cell differentiation, affecting gene expression both by repression and transcriptional activation. Still, this information is not used for classification of B-cell lymphomas (BCLs). Traditionally, BCLs are diagnosed based on a phenotypic resemblance to normal B-cells; assessed by immunohistochemistry or flow cytometry, by using a handful of phenotypic markers. In the last decade, diagnostic and prognostic evaluation has been facilitated by global gene expression profiling (GEP), providing a new powerful means for the classification, prediction of survival, and response to treatment of lymphomas. However, most GEP studies have typically been performed on whole tissue samples, containing varying degrees of tumor cell content, which results in uncertainties in data analysis. In this study, global GEP analyses were performed on highly purified, flow-cytometry sorted tumor-cells from eight subgroups of BCLs. This enabled identification of TFs that can be uniquely associated to the tumor cells of chronic lymphocytic leukemia (CLL), diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), hairy cell leukemia (HCL), and mantle cell lymphoma (MCL). The identified transcription factors influence both the global and specific gene expression of the BCLs and have possible implications for diagnosis and treatment.
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| 3. |
- Ekberg, S., et al.
(författare)
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Long-term survival and loss in expectancy of life in a population-based cohort of 7114 patients with diffuse large B-cell lymphoma
- 2018
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Ingår i: American Journal of Hematology. - : Wiley. - 0361-8609 .- 1096-8652. ; 93:8, s. 1020-1028
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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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| 4. |
- Glimelius, Ingrid, et al.
(författare)
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Long-term survival in young and middle-aged Hodgkin lymphoma patients in Sweden 1992-2009 - trends in cure proportions by clinical characteristics.
- 2015
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Ingår i: American Journal of Hematology. - : Wiley. - 0361-8609 .- 1096-8652. ; 90:12, s. 1128-1134
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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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| 5. |
- Wästerlid, Tove, et al.
(författare)
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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
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Ingår i: American Journal of Hematology. - : Wiley. - 0361-8609 .- 1096-8652. ; 95:7, s. 740-748
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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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