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Publications (10 of 18) Show all publications
Åström, M., Welander, E., Pourlotfi, A., Abawi, A., Ahlstrand, E. & Ivarsson, M. (2018). Activated interferon signaling in cultured BMSC from myelofibrosis patients: core finding of a proteomic study. In: : . Paper presented at 2nd International Conference on Tissue Repair, Regeneration, and Fibrosis, Chania, Crete, Greece, June 13-16, 2018.
Open this publication in new window or tab >>Activated interferon signaling in cultured BMSC from myelofibrosis patients: core finding of a proteomic study
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2018 (English)Conference paper, Poster (with or without abstract) (Refereed)
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:oru:diva-67255 (URN)
Conference
2nd International Conference on Tissue Repair, Regeneration, and Fibrosis, Chania, Crete, Greece, June 13-16, 2018
Available from: 2018-06-14 Created: 2018-06-14 Last updated: 2018-06-14Bibliographically approved
Åström, M., Tajeddinn, W., Karlsson, M. G., Linder, O., Palmblad, J. & Lindblad, P. (2018). Cytokine Measurements for Diagnosing and Characterizing Leukemoid Reactions and Immunohistochemical Validation of a Granulocyte Colony-Stimulating Factor and CXCL8-Producing Renal Cell Carcinoma. Biomarker Insights, 13, Article ID UNSP 1177271918792246.
Open this publication in new window or tab >>Cytokine Measurements for Diagnosing and Characterizing Leukemoid Reactions and Immunohistochemical Validation of a Granulocyte Colony-Stimulating Factor and CXCL8-Producing Renal Cell Carcinoma
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2018 (English)In: Biomarker Insights, ISSN 1177-2719, E-ISSN 1177-2719, Vol. 13, article id UNSP 1177271918792246Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Various paraneoplastic syndromes are encountered in renal cell carcinomas. This case report illustrates that a paraneoplastic leukemoid reaction may precede the diagnosis of renal cell carcinoma and be explained by cytokine production from the cancer cells.

CASE PRESENTATIONS: A 64-year-old man was referred for hematology workup due to pronounced leukocytosis. While being evaluated for a possible hematologic malignancy as the cause, he was found to have a metastasized renal cell carcinoma, and hyperleukocytosis was classified as a leukemoid reaction. A multiplex panel for measurement of 25 serum cytokines/chemokines showed highly elevated levels of granulocyte colony-stimulating factor (G-CSF) and CXCL8 (C-X-C-motif chemokine ligand 8, previously known as interleukin [IL]-8). By immunohistochemistry it was shown that the renal carcinoma cells expressed both these cytokines. Two additional, consecutive patients with renal cell carcinoma with paraneoplastic leukocytosis also showed elevated serum levels of CXCL8, but not of G-CSF. Nonparametric statistical evaluation showed significantly higher serum concentrations of CXCL8, IL-6, IL-10, monocyte chemoattractant protein 1 (MCP-1), and tumor necrosis factor, but lower interferon gamma (IFN-gamma) and IL-1 alpha, for the 3 renal cell carcinoma cases compared with healthy blood donors.

CONCLUSIONS: In suspected paraneoplastic leukocytosis, multiplex serum cytokine analyses may facilitate diagnosis and provide an understanding of the mechanisms for the reaction. In the index patient, combined G-CSF and CXCL8 protein expression by renal carcinoma cells was uniquely documented. A rapidly fatal course was detected in all 3 cases, congruent with the concept that autocrine/paracrine growth signaling in renal carcinoma cells may induce an aggressive tumor phenotype. Immune profiling studies could improve our understanding for possible targets when choosing therapies for patients with metastatic renal cell carcinoma.

Place, publisher, year, edition, pages
Sage Publications, 2018
Keywords
chemokine, IL-6, IL-10, monocytosis, paraneoplastic leukocytosis, autocrine signaling, multiplex, inflammatory response, precision medicine, biomarker
National Category
Immunology in the medical area Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:oru:diva-68648 (URN)10.1177/1177271918792246 (DOI)000441829800001 ()30147294 (PubMedID)
Available from: 2018-08-31 Created: 2018-08-31 Last updated: 2018-08-31Bibliographically approved
Welander, E., Åström, M., Enonge Fotabe, L., Kardeby, C., Tina, E., Elgbratt, K., . . . Ivarsson, M. (2018). Integrated analysis indicates reciprocal immune response dysregulations between bone marrow multipotent stromal cells and granulocytes at the mRNA but not at the protein level in myelofibrosis. In: : . Paper presented at Fortbildningsdagar i hematologi, Umeå, 3-5 Oktober, 2018.
Open this publication in new window or tab >>Integrated analysis indicates reciprocal immune response dysregulations between bone marrow multipotent stromal cells and granulocytes at the mRNA but not at the protein level in myelofibrosis
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2018 (English)Conference paper, Poster (with or without abstract) (Refereed)
National Category
Hematology
Identifiers
urn:nbn:se:oru:diva-69350 (URN)
Conference
Fortbildningsdagar i hematologi, Umeå, 3-5 Oktober, 2018
Available from: 2018-10-08 Created: 2018-10-08 Last updated: 2019-03-26Bibliographically approved
Lennmyr, E. B., Kozlowski, P., Ahlberg, L., Bernell, P., Hulegårdh, E., Izarra, A. S., . . . Swedish Adult Acute Lymphoblastic Leukemia Group (SVALL), G. A. (2018). Real-world data on first relapse of acute lymphoblastic leukemia in patients >55 years. Leukemia and Lymphoma, 59(10), 2470-2473
Open this publication in new window or tab >>Real-world data on first relapse of acute lymphoblastic leukemia in patients >55 years
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2018 (English)In: Leukemia and Lymphoma, ISSN 1042-8194, E-ISSN 1029-2403, Vol. 59, no 10, p. 2470-2473Article in journal (Refereed) Published
Place, publisher, year, edition, pages
Oxfordshire, United Kingdom: Taylor & Francis, 2018
National Category
Cancer and Oncology Hematology
Identifiers
urn:nbn:se:oru:diva-64503 (URN)10.1080/10428194.2017.1416369 (DOI)000455166400026 ()29345172 (PubMedID)
Note

Funding Agencies:

Lions Cancer Foundation  

Selander Foundation  

Thureus Foundation, Uppsala, Sweden 

Available from: 2018-01-25 Created: 2018-01-25 Last updated: 2019-01-23Bibliographically approved
Kozlowski, P., Lennmyr, E., Ahlberg, L., Bernell, P., Hulegårdh, E., Karbach, H., . . . The Swedish Adult Acute Lymphoblastic Leukemia Group (SVALL), G. a. (2017). Age but not Philadelphia positivity impairs outcome in older/elderly patients with acute lymphoblastic leukemia in Sweden. European Journal of Haematology, 99(2), 141-149
Open this publication in new window or tab >>Age but not Philadelphia positivity impairs outcome in older/elderly patients with acute lymphoblastic leukemia in Sweden
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2017 (English)In: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 99, no 2, p. 141-149Article in journal (Refereed) Published
Abstract [en]

OBJECTIVES: Older/elderly patients with acute lymphoblastic leukemia (ALL) are poorly represented in clinical trials.

METHODS: Using Swedish national leukemia registries, we investigated disease/patient characteristics, treatment choices, outcome, and the impact of an age-adapted protocol (introduced in 2009) in this population-based study of patients aged 55-85 years, diagnosed with ALL 2005-2012.

RESULTS: Of 174 patients, 82% had B-phenotype, 11% Burkitt leukemia (excluded), and 7% T-phenotype. Philadelphia chromosome positivity (Ph+) occurred in 35%. Of the 155 B- and T- ALL patients, 80% were treated with intensive protocols, and 20% with a palliative approach. Higher age and WHO performance status ≥2 influenced the choice of palliation. Intensive, palliative, and both approaches, resulted in complete remission rate 83/16/70%, and 3 year overall survival (OS) 32/3/26%. The age-adapted protocol did not improve outcome. With intensive treatment, platelet count ≤35 × 10(9) /L, and age ≥75 years were adverse prognostic factors for OS, Ph+ was not. Male sex was an adverse prognostic factor in the 55-64 year group.

CONCLUSIONS: We report a high frequency of Ph+ in older/elderly patients, with no evidence of poorer outcome compared to Ph negative disease. Overall prognosis for elderly patients with ALL remains dismal, despite the use of age-adapted treatment. This article is protected by copyright. All rights reserved.

Place, publisher, year, edition, pages
Wiley-Blackwell Publishing Inc., 2017
Keywords
acute lymphoblastic leukemia, chemotherapy, elderly, epidemiology
National Category
Hematology
Identifiers
urn:nbn:se:oru:diva-57317 (URN)10.1111/ejh.12896 (DOI)000404936400005 ()28419558 (PubMedID)2-s2.0-85020727975 (Scopus ID)
Note

Funding Agencies:

Research Committee of Region Orebro County Council (Orebro/Sweden)  

Lions Cancer Foundation (Uppsala/Sweden) 

Available from: 2017-05-30 Created: 2017-05-30 Last updated: 2018-09-06Bibliographically approved
Bergfelt, E., Kozlowski, P., Ahlberg, L., Bernell, P., Hulegårdh, E., Karbach, H., . . . Hallböök, H. (2016). RELAPSE OF ACUTE LYMPHOBLASTIC LEUKAEMIA IN OLDER/ELDERLY PATIENTS: A SWEDISH POPULATION-BASED STUDY. Paper presented at 21st Congress of the European-Hematology-Association, Copenhagen, Denmark, June 9-12, 2016. Haematologica, 101(Suppl. 1), 34-35
Open this publication in new window or tab >>RELAPSE OF ACUTE LYMPHOBLASTIC LEUKAEMIA IN OLDER/ELDERLY PATIENTS: A SWEDISH POPULATION-BASED STUDY
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2016 (English)In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 101, no Suppl. 1, p. 34-35Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
Pavia, Italy: Ferrata Storti Foundation, 2016
National Category
Hematology
Identifiers
urn:nbn:se:oru:diva-51735 (URN)000379484600074 ()
Conference
21st Congress of the European-Hematology-Association, Copenhagen, Denmark, June 9-12, 2016
Available from: 2016-08-23 Created: 2016-08-23 Last updated: 2017-11-28Bibliographically approved
Åström, M. (2015). Clinical cases: Presentation, diagnosis, treatment and follow-up: Case 2 - Chuvash polycythemia. In: Sylvie Hermouet (Ed.), Congenital Erythrocytosis and Hereditary Thrombocytosis: Clinical presentation, diagnosis, treatment and follow-up. A practical guide with clinical cases.. Portugal: European cooperation in science and technology
Open this publication in new window or tab >>Clinical cases: Presentation, diagnosis, treatment and follow-up: Case 2 - Chuvash polycythemia
2015 (English)In: Congenital Erythrocytosis and Hereditary Thrombocytosis: Clinical presentation, diagnosis, treatment and follow-up. A practical guide with clinical cases. / [ed] Sylvie Hermouet, Portugal: European cooperation in science and technology , 2015Chapter in book (Other academic)
Place, publisher, year, edition, pages
Portugal: European cooperation in science and technology, 2015
National Category
Hematology
Research subject
Medical Genetics
Identifiers
urn:nbn:se:oru:diva-45928 (URN)978-989-20-5646-3 (ISBN)
Available from: 2015-09-25 Created: 2015-09-25 Last updated: 2018-07-01Bibliographically approved
Bergfelt, E., Kozlowski, P., Åström, M., Ahlberg, L., Bernell, P., Hulegårdh, E., . . . Hallböök, H. (2015). Prognosis in older/elderly patients with acute lymphoblastic leukaemia diagnosed 2005-2012: results from a Swedish population-based study. Paper presented at 20th Congress of European-Hematology-Association, Vienna, Austria, June 11-14, 2015. Haematologica, 100(Suppl. 1), 202-202
Open this publication in new window or tab >>Prognosis in older/elderly patients with acute lymphoblastic leukaemia diagnosed 2005-2012: results from a Swedish population-based study
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2015 (English)In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 100, no Suppl. 1, p. 202-202Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
Pavia: Ferrata Storti Foundation, 2015
National Category
Hematology
Identifiers
urn:nbn:se:oru:diva-46175 (URN)000361204902037 ()
Conference
20th Congress of European-Hematology-Association, Vienna, Austria, June 11-14, 2015
Available from: 2015-10-19 Created: 2015-10-19 Last updated: 2018-07-02Bibliographically approved
Bergfelt, E., Kozlowski, P., Ahlberg, L., Hulegårdh, E., Hägglund, H., Karlsson, K., . . . Hallböök, H. (2015). Satisfactory outcome after intensive chemotherapy with pragmatic use of minimal residual disease (MRD) monitoring in older patients with Philadelphia-negative B cell precursor acute lymphoblastic leukaemia: a Swedish registry-based study. Medical Oncology, 32(4), Article ID 135.
Open this publication in new window or tab >>Satisfactory outcome after intensive chemotherapy with pragmatic use of minimal residual disease (MRD) monitoring in older patients with Philadelphia-negative B cell precursor acute lymphoblastic leukaemia: a Swedish registry-based study
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2015 (English)In: Medical Oncology, ISSN 1357-0560, E-ISSN 1559-131X, Vol. 32, no 4, article id 135Article in journal (Refereed) Published
Abstract [en]

The introduction of minimal residual disease (MRD) monitoring, in the Swedish national guidelines for acute lymphoblastic leukaemia, was evaluated in 35 patients aged 46-79 years (median 61), who were diagnosed from 2007 to 2011 and treated with high-intensity, block-based chemotherapy (ABCDV/VABA induction). Both a high complete remission rate (91 %) and acceptable overall survival (OS) rate (47 %) at 5 years were achieved. MRD by flow cytometry was measured in 73 % of the patients reaching complete remission after the first course, but was omitted by the clinicians for eight patients who were either over 70 years of age or already met conventional high-risk criteria. Factors negatively influencing OS were age over 65 years and WHO status >= 2. MRD < 0.1 % after induction had positive impact on continuous complete remission but not on OS. Only five patients were allocated to allogeneic haematopoietic stem cell transplantation in first remission, mainly due to conventional high risk factors. Thus, use of intensive remission induction therapy is effective in a selection of older patients. In a population for whom the possibilities of treatment escalation are limited, the optimal role of MRD monitoring remains to be determined.

Keywords
Acute lymphoblastic leukaemia, Adults, Minimal residual disease, Flow cytometry
National Category
Cancer and Oncology
Research subject
Oncology
Identifiers
urn:nbn:se:oru:diva-44342 (URN)10.1007/s12032-015-0582-2 (DOI)000351474100049 ()25796502 (PubMedID)
Note

Funding Agency:

Lions Cancer Research Foundation, Uppsala

Available from: 2015-04-20 Created: 2015-04-20 Last updated: 2018-06-29Bibliographically approved
Åström, M., Hahn-Strömberg, V., Zetterberg, E., Vedin, I., Merup, M. & Palmblad, J. (2015). X-linked thrombocytopenia with thalassemia displays bone marrow reticulin fibrosis and enhanced angiogenesis: comparisons with primary myelofibrosis. American Journal of Hematology, 90(3), E44-E48
Open this publication in new window or tab >>X-linked thrombocytopenia with thalassemia displays bone marrow reticulin fibrosis and enhanced angiogenesis: comparisons with primary myelofibrosis
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2015 (English)In: American Journal of Hematology, ISSN 0361-8609, E-ISSN 1096-8652, Vol. 90, no 3, p. E44-E48Article in journal (Refereed) Published
Abstract [en]

X-linked thrombocytopenia with thalassemia (XLTT) is caused by the mutation 216R > Q in exon 4 of the GATA1 gene. Male hemizygous patients display macrothrombocytopenia, splenomegaly, and a β-thalassemia trait. We describe two XLTT families where three males were initially misdiagnosed as having primary myelofibrosis (PMF) and all five investigated males showed mild-moderate bone marrow (BM) reticulin fibrosis. Comparative investigations were performed on blood samples and BM biopsies from males with XLTT, PMF patients and healthy controls. Like PMF, XLTT presented with high BM microvessel density, low GATA1 protein levels in megakaryocytes, and elevated blood CD34+ cell counts. But unlike PMF, the BM microvessel pericyte coverage was low in XLTT, and no collagen fibrosis was found. Further, as evaluated by immunohistochemistry, expressions of the growth factors VEGF, AGGF1, and CTGF were low in XLTT megakaryocytes and microvessels but high in PMF. Thus, although the reticulin fibrosis in XLTT might simulate PMF, opposing stromal and megakaryocyte features may facilitate differential diagnosis. Additional comparisons between these disorders may increase the understanding of mechanisms behind BM fibrosis in relation to pathological megakaryopoiesis.

National Category
Hematology
Identifiers
urn:nbn:se:oru:diva-43473 (URN)10.1002/ajh.23907 (DOI)000349889300003 ()25421114 (PubMedID)2-s2.0-84923092920 (Scopus ID)
Note

Funding Agencies:

Örebro County Council Research Committee OLL-158661  OLL-164431  OLL-239301  OLL-268261

Lions Cancer Research Foundation

Swedish Society of Hematology

Alexion

Available from: 2015-03-10 Created: 2015-03-10 Last updated: 2017-12-04Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-3384-4387

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