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Hedström, Gustaf
Alternative names
Publications (10 of 11) Show all publications
Gholiha, A. R., Hollander, P., Hedström, G., Sundström, C., Molin, D., Smedby, K. E., . . . Enblad, G. (2019). High tumour plasma cell infiltration reflects an important microenvironmental component in classic Hodgkin lymphoma linked to presence of B-symptoms. British Journal of Haematology, 184(2), 192-201
Open this publication in new window or tab >>High tumour plasma cell infiltration reflects an important microenvironmental component in classic Hodgkin lymphoma linked to presence of B-symptoms
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2019 (English)In: British Journal of Haematology, ISSN 0007-1048, E-ISSN 1365-2141, Vol. 184, no 2, p. 192-201Article in journal (Refereed) Published
Abstract [en]

Plasma cells are important prognostic actors in different malignancies. The tumour microenvironmental composition in classic Hodgkin lymphoma (cHL) is a major prognostic key element; however, clinicopathological studies regarding plasma cells in cHL are lacking. The aim of this study was to investigate CD138+ (also termed SDC1+) plasma cell and IgG4 producing (IgG4+) plasma cells infiltration in the microenvironment of cHL. Immunohistochemistry with anti-CD138 and IgG4 antibodies was performed on diagnostic tumour biopsies from 124 patients with cHL, on tissue micro array (TMA). In 120 cases, CD138+ plasma cell-infiltration was associated with the presence of B-symptoms (P = 0·028) and advanced stage, IIB-IVB (P = 0·009). In multivariate analysis, CD138+ plasma cells correlated with eosinophil infiltration (P = 0·013). The subgroup of IgG4+ plasma cells was analysed in 122 cases and only correlated to CD138+ plasma cells (P = 0·004). Patients with high proportion of tumour infiltrating CD138+ plasma cells (defined as ≥10%), had a more inferior event-free survival (P = 0·007) and overall survival (P = 0·004) than patients with a low proportion of infiltrating CD138+ plasma cells (<10%), although significance was not maintained in multivariate analysis. In summary, a high proportion of tumour-associated plasma cells in cHL reflect an important component in the microenvironment of cHL.

Keywords
CD138 plasma cells, Hodgkin's lymphoma, IgG4-producing plasma cells, Syndecan-1, tumour microenvironment
National Category
Cancer and Oncology Clinical Laboratory Medicine
Research subject
Pathology
Identifiers
urn:nbn:se:uu:diva-372809 (URN)10.1111/bjh.15703 (DOI)000455218700009 ()30506671 (PubMedID)
Available from: 2019-01-09 Created: 2019-01-09 Last updated: 2019-03-29Bibliographically approved
Abdulla, M., Laszlo, S., Triumf, J., Hedström, G., Berglund, M., Enblad, G. & Amini, R.-M. (2017). Core needle biopsies for the diagnosis of diffuse large B-cell lymphoma - a great concern for research [Letter to the editor]. Acta Oncologica, 56(1), 106-109
Open this publication in new window or tab >>Core needle biopsies for the diagnosis of diffuse large B-cell lymphoma - a great concern for research
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2017 (English)In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 56, no 1, p. 106-109Article in journal, Letter (Refereed) Published
National Category
Cancer and Oncology Clinical Laboratory Medicine
Research subject
Pathology
Identifiers
urn:nbn:se:uu:diva-317101 (URN)10.1080/0284186X.2016.1245863 (DOI)000392819600018 ()27796168 (PubMedID)
Available from: 2017-03-10 Created: 2017-03-10 Last updated: 2019-03-29Bibliographically approved
Mörth, C., Valachis, A., Abu Sabaa, A., Hedström, G., Flogegard, M. & Enblad, G. (2017). Does the omission of vincristine affect outcome and survival in patients with diffuse large B-cell lymphoma?. Paper presented at 42nd European-Society-for-Medical-Oncology Congress (ESMO), SEP 08-12, 2017, Madrid, SPAIN. Annals of Oncology, 28(S5), Article ID 1006PD.
Open this publication in new window or tab >>Does the omission of vincristine affect outcome and survival in patients with diffuse large B-cell lymphoma?
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2017 (English)In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 28, no S5, article id 1006PDArticle in journal, Meeting abstract (Other academic) Published
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-346980 (URN)000411324002194 ()
Conference
42nd European-Society-for-Medical-Oncology Congress (ESMO), SEP 08-12, 2017, Madrid, SPAIN
Available from: 2018-03-26 Created: 2018-03-26 Last updated: 2018-03-26Bibliographically approved
Hedström, G., Peterson, S., Berglund, M., Jerkeman, M. & Enblad, G. (2015). Male gender is an adverse risk factor only in young patients with diffuse large B-cell lymphoma - a Swedish population-based study. Acta Oncologica, 54(6), 924-932
Open this publication in new window or tab >>Male gender is an adverse risk factor only in young patients with diffuse large B-cell lymphoma - a Swedish population-based study
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2015 (English)In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 54, no 6, p. 924-932Article in journal (Refereed) Published
Abstract [en]

Background. Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous group of B-cell lymphomas. Five clinical adverse risk factors are merged into the International Prognostic Index (IPI), which is the major tool for prognostication. In contrast to Hodgkin's lymphoma, gender is not considered as an adverse risk factor for DLBCL patients. As we clinically had observed a very good survival rate in young female patients we hypothesised that there was a gender difference in survival due to the hormonal status of the patient. Material and methods. We conducted a registry-based retrospective cohort study of all Swedish DLBCL patients diagnosed between 2000 and 2013, to evaluate the impact of gender for survival from DLBCL. Results. In total, 7166 patients were included for further analysis. No survival difference was found between the genders when the entire population was analysed. However, analysis of 880 young patients of pre-menopausal age (i.e. 52 years) revealed that women had a longer survival compared to men of the same age group (p = 0.007). This was not found for patients older than menopausal age. In a relative survival multifactorial model adjusted for stage, ECOG performance status, serum lactate dehydrogenase and two or more extranodal sites, male gender was found to be an adverse risk factor for patients younger than 52 years (RR 1.51, 95% CI 1.14-1.88), but not for older patients (RR 0.99, 95% CI 0.89-1.10). Conclusion. This is one of the largest population-based studies of DLBCL presented to date. Most interestingly, we found male gender to be a significant adverse risk factor compared to fertile women whereas we found no survival differences between genders in the older sub-population.

National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-256117 (URN)10.3109/0284186X.2015.1026455 (DOI)000354479800016 ()25843161 (PubMedID)
Available from: 2015-06-23 Created: 2015-06-22 Last updated: 2017-12-04Bibliographically approved
Hedström, G., Hagberg, O., Jerkeman, M. & Enblad, G. (2015). The impact of age on survival of diffuse large B-cell lymphoma - a population-based study. Acta Oncologica, 54(6), 916-923
Open this publication in new window or tab >>The impact of age on survival of diffuse large B-cell lymphoma - a population-based study
2015 (English)In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 54, no 6, p. 916-923Article in journal (Refereed) Published
Abstract [en]

Background. For Diffuse large B-cell lymphoma (DLBCL), the International Prognostic Index is the major tool for prognostication and considers an age above 60 years as a risk factor. However, there are several indications that increasing age is associated with more biological complexity, resulting in differences in DLBCL biology depending on age. Methods. We conducted a registry-based retrospective cohort study of all Swedish DLBCL patients diagnosed 2000-2013, to evaluate the importance of age at diagnosis for survival of DLBCL patients. Results. In total, 7166 patients were included for further analysis. Survival declined for every 10-year age group and every age group above the age of 39 had a statistically decreased survival compared to the reference group of 20-29 years. In an analysis of relative survival, and in a multifactorial model adjusted for stage, ECOG performance status, serum lactate dehydrogenase and involvement of extranodal sites, each age group above age 39 had a significantly higher risk ratio (p = 0.01) compared to the reference group. Conclusion. This is one of the largest population-based studies of DLBCL published to date. In this study, age persisted as a signifi cant adverse risk factor for patients as young as 40 years, even after adjustment for other risk factors.

National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-256116 (URN)10.3109/0284186X.2014.978367 (DOI)000354479800015 ()25519707 (PubMedID)
Available from: 2015-06-23 Created: 2015-06-22 Last updated: 2017-12-04Bibliographically approved
Hedström, G., Hagberg, O., Jerkeman, M. & Enblad, G. (2014). Impact of age in an unselected population of Diffuse large B-cell lymphomas.
Open this publication in new window or tab >>Impact of age in an unselected population of Diffuse large B-cell lymphomas
2014 (English)Article in journal (Refereed) Submitted
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-219351 (URN)
Available from: 2014-02-27 Created: 2014-02-27 Last updated: 2014-06-05Bibliographically approved
Hedström, G. (2014). Prognostic Markers in Diffuse Large B-cell Lymphoma: How Bad can it be. (Doctoral dissertation). Uppsala: Acta Universitatis Upsaliensis
Open this publication in new window or tab >>Prognostic Markers in Diffuse Large B-cell Lymphoma: How Bad can it be
2014 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Diffuse large B-cell lymphoma (DLBCL), which is the most common type of lymphoma, is characterised by its aggressiveness and poor outcome without adequate treatment and also for its biological and clinical heterogeneity. It is therefore highly desirable to gain a more profound understanding of the underlying biology of the disease, as well as predictive factors for the guidance of treatment. The studies presented here attempt to gain an overall grasp on DLBCL, from the epidemiological level down to the genomic level.

The tumour microenvironment consists of both tumour cells and normal infiltrating cells in a delicate interplay. By assessing the number of infiltrating mast cells (MCs) in the microenvironment, a correlation between low numbers of MCs and poorer prognosis of DLBCL was found.

However, malignant cells are not only affected by environmental conditions but also by intrinsic factors, such as small non-coding microRNAs. A low expression level of microRNA-129 was found to correlate with poor survival of DLBCL and the finding remained significant even for rituximab-treated patients.

An even smaller intracellular genomic unit is one single nucleotide. The single nucleotide polymorphism 309 (SNP309) is a T to G change in the promotor region of MDM2, a regulatory protein in the p53 pathway, which results in increased transcription of MDM2 and thus decreased levels of p53. It was found that homozygous T allele patients had longer overall survival, as well as disease-specific survival and disease-free survival. However, treatment with rituximab eliminated the predictive value of the SNP309 polymorphism.

In the last project presented in this thesis we used epidemiological methods to analyse all DLBCL cases diagnosed 2000-2013 in Sweden. Here it was possible to categorically show that higher age is an adverse prognostic factor, and most importantly, this starts from a young age.

In conclusion, within this thesis I have applied different laboratory and analysis techniques to examine DLBCL biology in relation to the clinic. I have identified potential new prognostic markers, contributed to an enhanced understanding of DLBCL biology and described epidemiological data from one of the largest DLBCL cohorts ever presented. All of these aspects provide important information for a deeper understanding of the disease DLBCL. 

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2014. p. 85
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 978
Keywords
DLBCL, Survival, Mast cell, Microenvironment, MicroRNA, MDM2, Polymorphism, Age, Epidemiology
National Category
Cancer and Oncology
Research subject
Oncology
Identifiers
urn:nbn:se:uu:diva-220010 (URN)978-91-554-8896-3 (ISBN)
Public defence
2014-04-26, Auditorium Minus Gustavianum, Akademigatan 3, Uppsala, 09:15 (English)
Opponent
Supervisors
Available from: 2014-04-01 Created: 2014-03-09 Last updated: 2014-04-29
Hedström, G., Thunberg, U., Amini, R.-M., Zainuddin, N., Enblad, G. & Berglund, M. (2014). The MDM2 polymorphism SNP309 is associated with clinical characteristics and outcome in diffuse large B-cell lymphoma. European Journal of Haematology, 93(6), 500-508
Open this publication in new window or tab >>The MDM2 polymorphism SNP309 is associated with clinical characteristics and outcome in diffuse large B-cell lymphoma
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2014 (English)In: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 93, no 6, p. 500-508Article in journal (Refereed) Published
Abstract [en]

Introduction: The murine double minute 2 (MDM2) gene encodes a regulatory protein of the p53 pathway. A single nucleotide polymorphism (T to G change) at position 309 (SNP309) in the promotor region of MDM2 affects the transcription activity of MDM2 and has been found to be a negative prognostic marker in several cancers. Patients and methods: In this study, the MDM2 SNP309 polymorphism was analysed in 201 patients with diffuse large B-cell lymphoma and analysed in relation to clinical characteristics and prognosis. Results: Patients homozygous for SNP309T had a significantly longer overall survival, lymphoma-specific survival and disease-free survival (P = 0.002; 0.004 and 0.006 respectively) compared to patients carrying a G allele. The longer overall survival was seen in the subgroup of patients not treated with Rituximab, however, not for Rituximab-treated patients (P = 0.01 and 0.2 respectively). The group homozygous for the T allele also had lower age at diagnosis, a tendency towards lower aaIPI and a significantly lower proportion of patients with p53 aberrations compared to the group including at least one G allele. However, the survival differences persisted even after removal of cases with known p53 aberrations from the analysis. Conclusion: Polymorphism in MDM2 SNP309 could be correlated to some clinical characteristics and for patients not treated with immunotherapy, a G allele was correlated to poor survival, whereas no survival differences were found for patients treated with Rituximab. Herewith, we provide additional information about Diffuse large B-cell Lymphoma (DLBCL) biology and highlight the importance of evaluation of molecular markers in relation to treatment.

National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-219350 (URN)10.1111/ejh.12388 (DOI)000345302700006 ()24889555 (PubMedID)
Available from: 2014-02-27 Created: 2014-02-27 Last updated: 2017-12-05Bibliographically approved
Berglund, M., Hedström, G., Amini, R.-M., Enblad, G. & Thunberg, U. (2013). High expression of microRNA-200c predicts poor clinical outcome in diffuse large B-cell lymphoma. Oncology Reports, 29(2), 720-724
Open this publication in new window or tab >>High expression of microRNA-200c predicts poor clinical outcome in diffuse large B-cell lymphoma
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2013 (English)In: Oncology Reports, ISSN 1021-335X, E-ISSN 1791-2431, Vol. 29, no 2, p. 720-724Article in journal (Refereed) Published
Abstract [en]

Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous group of B-cell lymphomas. A new and important tool for understanding the biology and clinical course of DLBCL is microRNA expression. This study presents microRNA-200c expression data from 61 DLBCL patients treated with CHOP or R-CHOP. Patients with high microRNA-200c expression had a median survival of 20.3 months and a significantly shorter overall survival (P=0.019) compared to patients with low microRNA-200c expression, who had a median survival of 35.8 months. We also found that patients treated with R-CHOP only and displaying high microRNA-200c expression had a significantly shorter overall survival compared to patients with low microRNA-200c expression, where all patients were still alive at the time of the last follow-up (P=0.0036). Lastly, we found that patients with high microRNA-200c expression had a significantly shorter time from initial diagnosis to the first relapse compared to patients with low microRNA-200c expression (P=0.0001). To our knowledge, this is the first study showing that the expression of microRNA-200c affects the clinical outcome of DLBCL patients, and that microRNA-200c is involved in the biology of DLBCL development, although larger studies are necessary to confirm this. Further investigations may also help to elucidate the biological role of microRNA-200c in DLBCL.

Keywords
Diffuse large B-cell lymphoma, microRNA-200c, Prognosis
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-194853 (URN)10.3892/or.2012.2173 (DOI)000313605100043 ()
Available from: 2013-02-20 Created: 2013-02-19 Last updated: 2017-12-06Bibliographically approved
Hedström, G., Thunberg, U., Berglund, M., Simonsson, M., Amini, R.-M. & Enblad, G. (2013). Low expression of microRNA-129-5p predicts poor clinical outcome in diffuse large B cell lymphoma (DLBCL). International Journal of Hematology, 97(4), 465-471
Open this publication in new window or tab >>Low expression of microRNA-129-5p predicts poor clinical outcome in diffuse large B cell lymphoma (DLBCL)
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2013 (English)In: International Journal of Hematology, ISSN 0925-5710, E-ISSN 1865-3774, Vol. 97, no 4, p. 465-471Article in journal (Refereed) Published
Abstract [en]

Diffuse large B cell lymphoma (DLBCL) is a heterogeneous group of B cell lymphomas. MicroRNA expression provides a new and interesting tool for understanding the biology and clinical course of DLBCL. The present study presents microRNA-129-5p expression data from DLBCL patients treated with CHOP or R-CHOP. Patients with low microRNA-129-5p expression had a median survival of 23 months and a significantly shorter overall survival (P = 0.0042) compared to patients with high microRNA-129-5p expression, who had a median survival of 58 months. We also found that patients treated with R-CHOP only and displaying low microRNA-129-5p expression had a significantly shorter overall survival compared to patients with high microRNA-129-5p expression; all such patients were still alive at the time of last follow-up (P = 0.043). No significant difference was found among microRNA-129-5p expression in tumor tissue, the tissue surrounding the tumor, and normal controls. To our knowledge, this is the first report to show that the expression of microRNA-129-5p can affect the clinical outcome of DLBCL patients and that microRNA-129-5p may be involved in the biology of DLBCL development, although larger studies are necessary to confirm this. Further investigations may also help to elucidate the biological role of microRNA-129-5p in DLBCL.

Keywords
DLBCL, microRNA-129-5p, Prognosis
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-200079 (URN)10.1007/s12185-013-1303-2 (DOI)000317475500005 ()
Available from: 2013-05-23 Created: 2013-05-20 Last updated: 2017-12-06Bibliographically approved
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