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Uggla, Bertil
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Publications (10 of 22) Show all publications
Kozlowski, P., Kameran Behnam, K., Uggla, B. & Åström, M. (2020). Carfilzomib-induced hemolysis is noticeably common but rarely shows features of thrombotic microangiopathy: A retrospective study. European Journal of Haematology, 104(6), 588-593
Open this publication in new window or tab >>Carfilzomib-induced hemolysis is noticeably common but rarely shows features of thrombotic microangiopathy: A retrospective study
2020 (English)In: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 104, no 6, p. 588-593Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: Hemolysis is a sporadically reported but potentially serious side effect of the proteasome inhibitor carfilzomib. We aimed to investigate the frequency of hemolysis in an unselected cohort.

METHODS: We performed a retrospective, single-center study of the incidence of hemolysis in patients treated with carfilzomib, based mainly on consecutive haptoglobin levels. The patients were diagnosed with myeloma (n = 20), AL amyloidosis (n = 3), and light-chain deposition disease (n = 1). Carfilzomib treatment was applied after a median of 3 (range: 1-7) therapy lines.

RESULTS: Haptoglobin levels were normal/increased before, generally suppressed during, and normalized after treatment with carfilzomib. Very low haptoglobin (<0.1 g/L) implying the presence of hemolysis was observed in 16 of 24 (67%) patients during carfilzomib therapy. Hemolysis was mild in 11 of 16 (69%) affected patients, whereas 5 of 16 (31%) required transfusion. Severe hemolysis was explained by thrombotic microangiopathy (TMA) in one patient who died of the complication. Mechanisms were unclear in the remaining 15 patients.

CONCLUSIONS: Hemolysis was surprisingly common but mostly mild during carfilzomib treatment. However, the possibility of TMA should be kept in mind in this setting. Hypothetically, non-TMA hemolysis could be attributed to the accumulation of globin chains due to the suppression of eukaryotic translation initiation inhibition by carfilzomib.

Place, publisher, year, edition, pages
Munksgaard Forlag, 2020
Keywords
Hemolysis, neoplasia-myeloma and other plasma cell dyscrasias, proteasome inhibitors, thrombotic microangiopathies
National Category
Hematology
Identifiers
urn:nbn:se:oru:diva-80911 (URN)10.1111/ejh.13401 (DOI)000529825700009 ()32115785 (PubMedID)2-s2.0-85081718148 (Scopus ID)
Available from: 2020-03-30 Created: 2020-03-30 Last updated: 2020-05-18Bibliographically approved
Derolf, Å., Juliusson, G., Benson, L., Fløisand, Y., Lazarevic, V., Antunovic, P., . . . Deneberg, S. (2020). Decreasing early mortality in acute myeloid leukaemia in Sweden 1997-2014: improving performance status is a major contributing factor [Letter to the editor]. British Journal of Haematology, 188(1), 187-191
Open this publication in new window or tab >>Decreasing early mortality in acute myeloid leukaemia in Sweden 1997-2014: improving performance status is a major contributing factor
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2020 (English)In: British Journal of Haematology, ISSN 0007-1048, E-ISSN 1365-2141, Vol. 188, no 1, p. 187-191Article in journal, Letter (Refereed) Published
Place, publisher, year, edition, pages
Blackwell Publishing, 2020
National Category
Hematology
Identifiers
urn:nbn:se:oru:diva-79250 (URN)10.1111/bjh.16265 (DOI)000505278200021 ()31863470 (PubMedID)2-s2.0-85076746044 (Scopus ID)
Available from: 2020-01-20 Created: 2020-01-20 Last updated: 2020-01-20Bibliographically approved
Österroos, A., Eriksson, A., Antunovic, P., Cammenga, J., Deneberg, S., Lazarevic, V., . . . Lehmann, S. (2020). Real-world data on treatment patterns and outcomes of hypomethylating therapy in patients with newly diagnosed acute myeloid leukaemia aged ≥ 60 years [Letter to the editor]. British Journal of Haematology, 189(1), e13-e16
Open this publication in new window or tab >>Real-world data on treatment patterns and outcomes of hypomethylating therapy in patients with newly diagnosed acute myeloid leukaemia aged ≥ 60 years
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2020 (English)In: British Journal of Haematology, ISSN 0007-1048, E-ISSN 1365-2141, Vol. 189, no 1, p. e13-e16Article in journal, Letter (Refereed) Published
Place, publisher, year, edition, pages
Blackwell Science Ltd., 2020
National Category
Cancer and Oncology Hematology
Identifiers
urn:nbn:se:oru:diva-80309 (URN)10.1111/bjh.16410 (DOI)000516518800001 ()32103493 (PubMedID)2-s2.0-85079056210 (Scopus ID)
Available from: 2020-03-03 Created: 2020-03-03 Last updated: 2020-04-01Bibliographically approved
Vaht, K., Göransson, M., Carlson, K., Isaksson, C., Lenhoff, S., Sandstedt, A., . . . Brune, M. (2019). High Graft-versus-Host Disease-Free, Relapse/Rejection-Free Survival and Similar Outcome of Related and Unrelated Allogeneic Stem Cell Transplantation for Aplastic Anemia: A Nationwide Swedish Cohort Study. Biology of blood and marrow transplantation, 25(10), 1970-1974
Open this publication in new window or tab >>High Graft-versus-Host Disease-Free, Relapse/Rejection-Free Survival and Similar Outcome of Related and Unrelated Allogeneic Stem Cell Transplantation for Aplastic Anemia: A Nationwide Swedish Cohort Study
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2019 (English)In: Biology of blood and marrow transplantation, ISSN 1083-8791, E-ISSN 1523-6536, Vol. 25, no 10, p. 1970-1974Article in journal (Refereed) Published
Abstract [en]

Allogeneic stem cell transplantation (SCT) as primary treatment for aplastic anemia (AA) is being increasingly used. Yet, age, stem cell source, and donor type are important outcome factors. We have recently performed a nationwide cohort study of all patients with AA in Sweden diagnosed from 2000 to 2011 and now present outcome data on SCT patients. In total, 68 patients underwent SCT, and 63% of them had failed immunosuppressive therapy. We found that, with a median follow-up of 109 months (range, 35 to 192 months), 5-year overall survival (OS) for all patients was 86.8%, whereas graft-versus-host disease-free, relapse/rejection-free survival (GRFS) at 5 years was 69.1%. There was no survival impact regarding the donor type or stem cell source. Patients aged >= 40 years had a higher transplant-related mortality (29.4% versus 7.8%; P= .023), which translated into a lower 5-year OS: 70.6% versus 92.2% (A=.022) and a trend of lower GRFS (52.9% versus 74.5%; P = .069). In conclusion, we found in this real-world setting that both OS and GRFS were high, but SCT for patients with AA aged >= 40 years is problematic, and clinical trials addressing this issue are warranted. (C) 2019 American Society for Transplantation and Cellular Therapy.

Place, publisher, year, edition, pages
Elsevier, 2019
Keywords
Aplastic anemia, Allogenic stem cell transplantation, Graft-versus-host disease-free, Relapse/rejection-free survival, Real-world data
National Category
Hematology Immunology in the medical area
Identifiers
urn:nbn:se:oru:diva-77818 (URN)10.1016/j.bbmt.2019.05.032 (DOI)000492801700008 ()31173901 (PubMedID)2-s2.0-85068208816 (Scopus ID)
Note

Funding Agencies:

Gothenburg Medical Society

Borås Cancer Foundation  

Swedish government  

ALF  ALFGBG-719481

Available from: 2019-11-12 Created: 2019-11-12 Last updated: 2019-11-12Bibliographically approved
Vaht, K., Göransson, M., Carlson, K., Isaksson, C., Lenhoff, S., Sandstedt, A., . . . Andersson, P.-O. (2018). Low response rate to ATG-based immunosuppressive therapy in very severe aplastic anaemia: A Swedish nationwide cohort study. European Journal of Haematology, 100(6), 613-620
Open this publication in new window or tab >>Low response rate to ATG-based immunosuppressive therapy in very severe aplastic anaemia: A Swedish nationwide cohort study
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2018 (English)In: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 100, no 6, p. 613-620Article in journal (Refereed) Published
Abstract [en]

Objectives: Antithymocyte globulin (ATG)-based immunosuppression remains a cornerstone in aplastic anaemia (AA) treatment. However, most ATG studies are not population-based and knowledge about real-world results concerning response and outcome could offer important information for treating physicians.

Methods: We have recently performed a nationwide retrospective cohort study on all AA patients diagnosed in Sweden in 2000–2011 and now present treatment and outcome data on patients receiving first-line ATG. In total, 158 patients showed a 47.0% response rate which was similar in all age groups (range 41.5%-51.7%) with no difference regarding ATG formulation. The response was significantly associated with severity grade—especially at time of treatment initiation: very severe (VSAA) 22.7%; severe (SAA) 54.5% (P <.001); and non-severe 88.5% (P <.001). A logistic regression-based predictive model indicated that VSAA patients with an absolute reticulocyte count <25 × 109/L had only a 19% probability of response. In a multivariable analysis, age and VSAA at the time of treatment were the independent factors for inferior survival.

Conclusions: Real-world VSAA patients respond poorly to ATG which indicates the need for a different treatment approach. Our findings suggest that age alone should not be a discriminating factor for administering ATG treatment.

Place, publisher, year, edition, pages
Munksgaard Forlag, 2018
Keywords
Age, antithymocyte globulin, aplastic anaemia, real-world data, response rate
National Category
Hematology
Identifiers
urn:nbn:se:oru:diva-67146 (URN)10.1111/ejh.13057 (DOI)000434100400011 ()29532518 (PubMedID)2-s2.0-85045037330 (Scopus ID)
Note

Funding Agencies:

Göteborgs Läkaresällskap  

ALF Västra Götaland 

Available from: 2018-06-04 Created: 2018-06-04 Last updated: 2018-06-20Bibliographically approved
Lehmann, S., Deneberg, S., Antunovic, P., Rangert-Derolf, Å., Garelius, H. K. G., Lazarevic, V. L., . . . Juliusson, G. J. (2017). Early death rates remain high in high-risk APL: update from the Swedish Acute Leukemia Registry 1997-2013. Leukemia, 31(6), 1457-1459
Open this publication in new window or tab >>Early death rates remain high in high-risk APL: update from the Swedish Acute Leukemia Registry 1997-2013
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2017 (English)In: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 31, no 6, p. 1457-1459Article in journal (Refereed) Published
Place, publisher, year, edition, pages
Nature Publishing Group, 2017
National Category
Hematology Cancer and Oncology
Identifiers
urn:nbn:se:oru:diva-57394 (URN)10.1038/leu.2017.71 (DOI)000402832700028 ()28232742 (PubMedID)2-s2.0-85016181607 (Scopus ID)
Note

All authors are members of 

Unit of Hematology, Department of Medicine, Karolinska Institute, Huddinge, Stockholm, Sweden

Available from: 2017-05-03 Created: 2017-05-03 Last updated: 2017-09-06Bibliographically approved
Vaht, K., Göransson, M., Carlson, K., Isaksson, C., Lenhoff, S., Sandstedt, A., . . . Andersson, P.-O. (2017). Incidence and outcome of acquired aplastic anemia: real-world data from patients diagnosed in Sweden from 2000-2011. Haematologica, 102(10), 1683-1690
Open this publication in new window or tab >>Incidence and outcome of acquired aplastic anemia: real-world data from patients diagnosed in Sweden from 2000-2011
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2017 (English)In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 102, no 10, p. 1683-1690Article in journal (Refereed) Published
Abstract [en]

A plastic anemia is a rare life-threatening disease. However, since the introduction of immunosuppressive therapy and allogeneic stem cell transplantation, the outcome has improved considerably, and the 5-year survival is reported to be 70-80% in selected patient cohorts. Yet, contemporary population-based data on incidence and survival are lacking. We performed a national retrospective study to determine the incidence, treatment, and survival of patients with aplastic anemia diagnosed in Sweden from 2000-2011. Patients were included via the National Patient Registry, and diagnosed according to the Camitta criteria. In total, 257 confirmed cases were identified, with an overall incidence of 2.35 (95% CI: 2.06-2.64) cases per million inhabitants per year. Median age was 60 years (range: 2-92), and median follow up was 76 (0-193) months. Primary treatments included immunosuppressive therapy (63%), allogenic stem cell transplantation (10%), or single-agent cyclosporine/no specific therapy (27%). The 5-year survival was 90.7% in patients aged 0-18 years, 90.5% in patients aged 19-39 years, 70.7% in patients aged 40-59 years, and 38.1% in patients aged ≥60 years. Multivariate analysis showed that age (both 40-59 and ≥60 age groups), very severe aplastic anemia and single-agent cyclosporine/no specific therapy were independent risk factors for inferior survival. In conclusion, younger aplastic anemia patients experience a very good long-term survival, while that of patients ≥60 years in particular remains poor. Apparently, the challenge today is to improve the management of older aplastic anemia patients, and prospective studies to address this medical need are warranted.

Place, publisher, year, edition, pages
Pavia, Italy: Ferrata Storti Foundation, 2017
National Category
Hematology
Identifiers
urn:nbn:se:oru:diva-61464 (URN)10.3324/haematol.2017.169862 (DOI)000411964200020 ()28751565 (PubMedID)2-s2.0-85030308835 (Scopus ID)
Note

Funding Agencies:

ALF Vastra Gotaland

Gothenburg Medical Society 

Alexion Sweden 

Available from: 2017-10-13 Created: 2017-10-13 Last updated: 2018-08-06Bibliographically approved
Lazarevic, V. L., Rosso, A., Juliusson, G., Antunovic, P., Derolf, Å. R., Deneberg, S., . . . Johansson, B. (2017). Incidence and prognostic significance of isolated trisomies in adult acute myeloid leukemia: A population-based study from the Swedish AML registry. European Journal of Haematology, 98(5), 493-500
Open this publication in new window or tab >>Incidence and prognostic significance of isolated trisomies in adult acute myeloid leukemia: A population-based study from the Swedish AML registry
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2017 (English)In: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 98, no 5, p. 493-500Article in journal (Refereed) Published
Abstract [en]

OBJECTIVES AND METHODS: To ascertain the incidence/clinical implications of isolated autosomal trisomies in adult acute myeloid leukemia (AML), all such cases were retrieved from the Swedish AML Registry.

RESULTS: Of the 3179 cytogenetically informative AMLs diagnosed January 1997-May 2015, 246 (7.7%) had isolated trisomies. The frequency increased by age (2.4% at age 18-60 years vs. 23% at >60 years; P<.0001); the median age was 69 years. The five most common were +8 (4.0%), +13 (0.9%), +11 (0.8%), +21 (0.7%), and +4 (0.5%). Age and gender, types of AML and treatment, and complete remission and early death rates did not differ between the single trisomy and the intermediate risk (IR) groups or among cases with isolated gains of chromosomes 4, 8, 11, 13, or 21. The overall survival (OS) was similar in the single trisomy (median 1.6 years) and IR groups (1.7 years; P=.251). The OS differed among the most frequent isolated trisomies; the median OS was 2.5 years for +4, 1.9 years for +21, 1.5 years for +8, 1.1 years for +11, and 0.8 years for +13 (P=.013).

CONCLUSION: AML with single trisomies, with the exception of +13, should be grouped as IR.

Place, publisher, year, edition, pages
John Wiley & Sons, 2017
Keywords
acute myeloid leukemia, autosomal trisomy, clinical characteristics, survival
National Category
Cancer and Oncology Hematology
Research subject
Oncology; Cancer Epidemiology
Identifiers
urn:nbn:se:oru:diva-57401 (URN)10.1111/ejh.12861 (DOI)000399882100009 ()28152233 (PubMedID)2-s2.0-85014778341 (Scopus ID)
Funder
Swedish Research CouncilSwedish Cancer Society
Note

Funding Agencies:

Regional Cancer Centers 

Swedish Association of Local Authorities and Regions (SKL)  

Governmental Funding of Clinical Research within the National Health Service 

Available from: 2017-05-02 Created: 2017-05-02 Last updated: 2017-09-06Bibliographically approved
Lazarevic, V., Hörstedt, A.-S., Johansson, B., Antunovic, P., Billström, R., Derolf, A., . . . Juliusson, G. (2015). Failure matters: unsuccessful cytogenetics and unperformed cytogenetics are associated with a poor prognosis in a population-based series of acute myeloid leukaemia. European Journal of Haematology, 94(5), 419-423
Open this publication in new window or tab >>Failure matters: unsuccessful cytogenetics and unperformed cytogenetics are associated with a poor prognosis in a population-based series of acute myeloid leukaemia
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2015 (English)In: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 94, no 5, p. 419-423Article in journal (Refereed) Published
Abstract [en]

Unsuccessful cytogenetics (UC) in patients with acute myeloid leukaemia (AML) treated on different SWOG trials was recently reported to be associated with increased age and dismal outcome. To ascertain whether this holds true also in unselected patients with AML, we retrieved all cytogenetic reports in cases from the population-based Swedish AML Registry. Between 1997 and 2006, 1737 patients below 80 yr of age without myelosarcoma or acute promyelocytic leukaemia received intensive treatment. The frequencies of UC and unperformed cytogenetics (UPC) were 2.1% and 20%, respectively. The early death rates differed between the cytogenetic subgroups (P = 0.006) with the highest rates in patients with UC (14%) and UPC (12%) followed by high-risk (HR) AML, intermediate risk (IR) and standard risk (SR) cases successfully karyotyped (8.6%, 5.9%, and 5.8%, respectively). The complete remission rate was lower in UC and UPC and HR compared with the other risk groups (P < 0.001). The overall five-year survival rates were 25% for UC and 22% for UPC, whereas the corresponding frequencies for SR, IR and HR AML patients without UC and UPC were 64%, 31% and 15%, respectively. In conclusion, lack of cytogenetic data translates into a poor prognosis.

Place, publisher, year, edition, pages
Hoboken, USA: Wiley-Blackwell, 2015
Keywords
unsuccessful metaphase analysis; Unperformed cytogenetics, acute myeloid leukaemia, karyotype, survival
National Category
Medical and Health Sciences Hematology
Identifiers
urn:nbn:se:oru:diva-37791 (URN)10.1111/ejh.12446 (DOI)000352633000007 ()25200361 (PubMedID)2-s2.0-84926476133 (Scopus ID)
Available from: 2014-10-15 Created: 2014-10-15 Last updated: 2018-06-26Bibliographically approved
Uggla, B. & Nilsson, T. (2015). Whole blood viscosity in plasma cell dyscrasias. Clinical Biochemistry, 48(3), 122-124
Open this publication in new window or tab >>Whole blood viscosity in plasma cell dyscrasias
2015 (English)In: Clinical Biochemistry, ISSN 0009-9120, E-ISSN 1873-2933, Vol. 48, no 3, p. 122-124Article in journal (Refereed) Published
Abstract [en]

Objectives: Plasma or serum hyperviscosity in plasma cell dyscrasias (PCD) has been described as a risk factor for circulatory disturbances. Whole blood viscosity (WBV) would theoretically be a better biomarker but has not been studied in PCD.

Design and methods: Plasma viscosity (PV) and WBV were measured in 89 subjects with PCD and in 60 healthy blood donors by free oscillation rheometry. A complete blood count was obtained using an automated hematology analyzer. Plasma proteins were quantitated by immunoturbidimetry.

Results: The reference intervals for men & women were 1.16-1.36 & 1.16-1.38. mPa for PV, and 4.9-6.3 & 4.4-6.2. mPa for WBV, respectively. Of the PCD patients, 71% had PV above the reference limit and 40% were above the WBV limit. Multivariate analysis showed that WBV was independently related to hematocrit, PV, concentration of the monoclonal protein (M-protein), plasma fibrinogen concentration and albumin concentration. This model accounted for 76% of the variance in WBV. When the same model was applied to PV, only the concentration of the M-protein was significantly related and the model accounted only for 20% of the variance in PV.

Conclusion: PV cannot be used as a surrogate marker for WBV in PCD patients. Whole blood viscosity should replace plasma viscosity in patients with PCD.

Place, publisher, year, edition, pages
Elsevier, 2015
Keywords
M-protein; MGUS; Myeloma; Plasma viscosity; Whole blood viscosity
National Category
Medical and Health Sciences
Research subject
Medicine
Identifiers
urn:nbn:se:oru:diva-41639 (URN)10.1016/j.clinbiochem.2014.11.006 (DOI)000348703300006 ()25526882 (PubMedID)2-s2.0-84921765352 (Scopus ID)
Note

Funding Agency:

Örebro County Council Research Committee

Available from: 2015-01-15 Created: 2015-01-15 Last updated: 2017-12-05Bibliographically approved
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