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Wahlin, Anders
Publications (10 of 55) Show all publications
Thunström Salzer, A., Niemiec, M. J., Hosseinzadeh, A., Stylianou, M., Åstrom, F., Röhm, M., . . . Urban, C. F. (2018). Assessment of Neutrophil Chemotaxis Upon G-CSF Treatment of Healthy Stem Cell Donors and in Allogeneic Transplant Recipients. Frontiers in Immunology, 9, Article ID 1968.
Open this publication in new window or tab >>Assessment of Neutrophil Chemotaxis Upon G-CSF Treatment of Healthy Stem Cell Donors and in Allogeneic Transplant Recipients
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2018 (English)In: Frontiers in Immunology, ISSN 1664-3224, E-ISSN 1664-3224, Vol. 9, article id 1968Article in journal (Refereed) Published
Abstract [en]

Neutrophils are crucial for the human innate immunity and constitute the majority of leukocytes in circulation. Thus, blood neutrophil counts serve as a measure for the immune system's functionality. Hematological patients often have low neutrophil counts due to disease or chemotherapy. To increase neutrophil counts and thereby preventing infections in high-risk patients, recombinant G-CSF is widely used as adjunct therapy to stimulate the maturation of neutrophils. In addition, G-CSF is utilized to recruit stem cells (SCs) into the peripheral blood of SC donors. Still, the actual functionality of neutrophils resulting from G-CSF treatment remains insufficiently understood. We tested the ex vivo functionality of neutrophils isolated from blood of G-CSF-treated healthy SC donors. We quantified chemotaxis, oxidative burst, and phagocytosis before and after treatment and detected significantly reduced chemotactic activity upon G-CSF treatment. Similarly, in vitro treatment of previously untreated neutrophils with G-CSF led to reduced chemotactic activity. In addition, we revealed that this effect persists in the allogeneic SC recipients up to 4 weeks after neutrophil engraftment. Our data indicates that neutrophil quantity, as a sole measure of immunocompetence in high-risk patients should be considered cautiously as neutrophil functionality might be affected by the primary treatment.

Place, publisher, year, edition, pages
Frontiers Media S.A., 2018
Keywords
neutrophil, granulocyte colony stimulating factor (G-CSF), allogeneic transplant, chemotaxis, hematopoietic stern cell donor
National Category
Immunology in the medical area
Identifiers
urn:nbn:se:umu:diva-152255 (URN)10.3389/fimmu.2018.01968 (DOI)000444324800001 ()30254629 (PubMedID)
Funder
Västerbotten County Council
Available from: 2018-10-03 Created: 2018-10-03 Last updated: 2018-10-03Bibliographically approved
Lorenz, F., Pawlowicz, E., Klimkowska, M., Beshara, S., Brustad, A. B., Skotnicki, A. B., . . . Machaczka, M. (2018). Ferritinemia and serum inflammatory cytokines in Swedish adults with Gaucher disease type 1. Blood Cells, Molecules & Diseases, 68, 35-42
Open this publication in new window or tab >>Ferritinemia and serum inflammatory cytokines in Swedish adults with Gaucher disease type 1
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2018 (English)In: Blood Cells, Molecules & Diseases, ISSN 1079-9796, E-ISSN 1096-0961, Vol. 68, p. 35-42Article in journal (Refereed) Published
Abstract [en]

Background: The storage of glucosylceramide in macrophages produces an inflammatory response in Gaucher disease type 1 (GD1) resulting in iron metabolism dysregulation and cytokine release. Patients and methods: The study included 16 adults with GD1 aged 20-86 years. All but one patient carried at least one allele with the c.1226A > G (N370S) mutation in the GBA1 gene. Ferritinemia, iron metabolism profiles including hepcidin, and inflammatory cytokine concentrations were assessed in GD1 patients in Sweden. Results: Hyperferritinemia was present in 81% of patients. There was no correlation between hyperferritinemia and patient's gender, spleen status, or clinical status. Hepcidin was discrepantly low in relation to ferritin levels. TNF-alpha was moderately increased in 5 of 11 patients; 2 patients with the highest TNF-alpha concentrations showed mildly elevated IL-6 levels. The concentrations of IL-1 beta, IL-8, and IL-10 were normal in all patients. Upon treatment, ferritinemia ameliorated but S-ferritin levels did not normalize. The increased TNF-alpha level however, normalized in all treated patients, reaching the lowest values after 2 years of therapy and continued to be stable during the remaining 2 years of follow-up. Conclusions: Hyperferritinemia is a frequent finding in GD1 in Sweden. The relatively low hepcidin levels reveal a distorted relationship between hepcidin and ferritin in GD1. Therapy has the potential to not only ameliorate hyperferritinemia but to also normalize the serum TNF-alpha concentration in GD1. 

Place, publisher, year, edition, pages
ACADEMIC PRESS INC ELSEVIER SCIENCE, 2018
Keywords
Gaucher disease, Hyperferritinemia, Cytokines, TNF-alpha, Enzyme replacement therapy, Substrate reduction therapy
National Category
Hematology
Identifiers
urn:nbn:se:umu:diva-143707 (URN)10.1016/j.bcmd.2016.10.010 (DOI)000417147400009 ()27816428 (PubMedID)
Available from: 2018-01-08 Created: 2018-01-08 Last updated: 2018-06-09Bibliographically approved
Lazarevic, V. L., Rosso, A., Juliusson, G., Antunovic, P., Derolf, A. 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.

Keywords
acute myeloid leukemia, autosomal trisomy, clinical characteristics, survival
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-135271 (URN)10.1111/ejh.12861 (DOI)000399882100009 ()28152233 (PubMedID)
Available from: 2017-05-26 Created: 2017-05-26 Last updated: 2018-06-09Bibliographically approved
Liljeholm, M., Vikberg, A.-L., Golovleva, I., Sandström, H. & Wahlin, A. (2016). Congenital Dyserythropoietic Anemia Type III and Primary Hemochromatosis; Coexistence of Mutations in KIF23 and HFE.. Journal of Hematology and Blood Disorders, 1(2), Article ID 203.
Open this publication in new window or tab >>Congenital Dyserythropoietic Anemia Type III and Primary Hemochromatosis; Coexistence of Mutations in KIF23 and HFE.
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2016 (English)In: Journal of Hematology and Blood Disorders, Vol. 1, no 2, article id 203Article in journal (Refereed) Published
Abstract [en]

Background: Congenital dyserythropoietic anemia type III (CDA III) can be caused by mutation in KIF23. CDA III differs from CDA I and II in the sense that secondary hemochromatosis has not been reported. However, we have observed elevated serum ferritin in a CDA III family. Since primary hemochromatosis is common in Northern Europe we decided to screen the family for HFE mutations.

Aim: Study clinical appearance and prevalence of HFE gene mutations, C282Y and H63D, in a CDA III family. 

Methods: DNA from 37 CDA III patients and 21 non-affected siblings was genotyped. Iron status from EDTA plasma was measured in 32 of the CDA III patients and 18 of the non-affected siblings.

Results: Out of 37 CDA III patients, 18 carried heterozygous HFE mutations and six were compound heterozygotes. Out of 21 CDA III negative siblings, nine had heterozygous HFE mutations, two were homozygous (one H63D and one C282Y), and two were compound heterozygous. None of the patients with wt HFE, regardless of CDA III status, suffered from iron overload. Four patients with HFE mutations needed treatment with phlebotomy to normalize ferritin and transferrin iron saturation; one CDA III negative patient with homozygous C282Y, two CDA III patients with heterozygous HFE mutations and one CDA III case with compound heterozygosity.

Conclusion: HFE mutations were found in 65 % of CDA III patients and in 62 % of their CDA III negative siblings. Heterozygous HFE mutation, C282Y and even H63D, can cause iron overload when occurring concomitantly with CDA III.

Place, publisher, year, edition, pages
Annex Publishers, 2016
Keywords
Congenital dyserythropoietic anemia; Hereditary hemochromatosis; Iron overload; HFE gene; KIF23 gene
National Category
Hematology
Identifiers
urn:nbn:se:umu:diva-117453 (URN)
Available from: 2016-02-29 Created: 2016-02-29 Last updated: 2018-06-07Bibliographically approved
Jonsdottir, G., Lund, S. H., Björkholm, M., Turesson, I., Wahlin, A., Mailankody, S., . . . Kristinsson, S. Y. (2016). Survival in multiple myeloma patients who develop second malignancies: a population-based cohort study [Letter to the editor]. Haematologica, 101(4), e145-e148
Open this publication in new window or tab >>Survival in multiple myeloma patients who develop second malignancies: a population-based cohort study
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2016 (English)In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 101, no 4, p. e145-e148Article in journal, Letter (Refereed) Published
Place, publisher, year, edition, pages
Ferrata Storti Foundation, 2016
Keywords
multiple myeloma, second malignancy, survival, population-based
National Category
Hematology
Identifiers
urn:nbn:se:umu:diva-124269 (URN)10.3324/haematol.2015.134049 (DOI)000379393100007 ()26681760 (PubMedID)
Available from: 2016-08-01 Created: 2016-07-29 Last updated: 2018-06-07Bibliographically approved
Hulegårdh, E., Nilsson, C., Lazarevic, V., Garelius, H., Antunovic, P., Rangert Derolf, Å., . . . Lehmann, S. (2015). Characterization and prognostic features of secondary acute myeloid leukemia in a population-based setting: A report from the Swedish Acute Leukemia Registry. American Journal of Hematology, 90(3), 208-214
Open this publication in new window or tab >>Characterization and prognostic features of secondary acute myeloid leukemia in a population-based setting: A report from the Swedish Acute Leukemia Registry
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2015 (English)In: American Journal of Hematology, ISSN 0361-8609, E-ISSN 1096-8652, Vol. 90, no 3, p. 208-214Article in journal (Refereed) Published
Abstract [en]

Patients with secondary acute myeloid leukemia (AML) often escape inclusion in clinical trials and thus, population-based studies are crucial for its accurate characterization. In this first large population-based study on secondary AML, we studied AML with an antecedent hematological disease (AHD-AML) or therapy-related AML (t-AML) in the population-based Swedish Acute Leukemia Registry. The study included 3,363 adult patients of which 2,474 (73.6%) had de novo AML, 630 (18.7%) AHD-AML, and 259 (7.7%) t-AML. Secondary AML differed significantly compared to de novo AML with respect to age, gender, and cytogenetic risk. Complete remission (CR) rates were significantly lower but early death rates similar in secondary AML. In a multivariable analysis, AHD-AML (HR 1.51; 95% CI 1.26-1.79) and t-AML (1.72; 1.38-2.15) were independent risk factors for poor survival. The negative impact of AHD-AML and t-AML on survival was highly age dependent with a considerable impact in younger patients, but without independent prognostic value in the elderly. Although patients with secondary leukemia did poorly with intensive treatment, early death rates and survival were significantly worse with palliative treatment. We conclude that secondary AML in a population-based setting has a striking impact on survival in younger AML patients, whereas it lacks prognostic value among the elderly patients.

National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-101381 (URN)10.1002/ajh.23908 (DOI)000349889300014 ()25421221 (PubMedID)
Available from: 2015-07-08 Created: 2015-03-30 Last updated: 2018-06-07Bibliographically approved
Liljeholm, M., Vikberg, A.-L., Golovleva, I. & Wahlin, A. (2015). Congenital dyserythropoietic anemia type III and primary hemochromatosis; coexistence of mutations in KIF23 and HFE. Paper presented at 20th Congress of European-Hematology-Association, JUN 11-14, 2015, Vienna, AUSTRIA. Haematologica, 100, 594-594
Open this publication in new window or tab >>Congenital dyserythropoietic anemia type III and primary hemochromatosis; coexistence of mutations in KIF23 and HFE
2015 (English)In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 100, p. 594-594Article in journal, Meeting abstract (Other academic) Published
National Category
Hematology
Identifiers
urn:nbn:se:umu:diva-110214 (URN)000361204904023 ()
Conference
20th Congress of European-Hematology-Association, JUN 11-14, 2015, Vienna, AUSTRIA
Note

Supplement: 1Meeting Abstract: E1481

Available from: 2015-10-16 Created: 2015-10-16 Last updated: 2018-06-07Bibliographically approved
Lazarevic, V., Hörstedt, A.-S., Johansson, B., Antunovic, P., Billström, R., Derolf, Å., . . . 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 80yr 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
John Wiley & Sons, 2015
Keywords
unsuccessful metaphase analysis, unperformed cytogenetics, acute myeloid leukaemia, karyotype, survival
National Category
Clinical Medicine
Identifiers
urn:nbn:se:umu:diva-103131 (URN)10.1111/ejh.12446 (DOI)000352633000007 ()25200361 (PubMedID)
Available from: 2015-05-29 Created: 2015-05-18 Last updated: 2018-06-07Bibliographically approved
Lazarevic, V., Rosso, A., Juliusson, G., Antunovic, P., Rangert-Derolf, A., Lehmann, S., . . . Johansson, B. (2015). Prognostic significance of high hyperdiploid and triploid/tetraploid adult acute myeloid leukemia. American Journal of Hematology, 90(9), 800-805
Open this publication in new window or tab >>Prognostic significance of high hyperdiploid and triploid/tetraploid adult acute myeloid leukemia
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2015 (English)In: American Journal of Hematology, ISSN 0361-8609, E-ISSN 1096-8652, Vol. 90, no 9, p. 800-805Article in journal (Refereed) Published
Abstract [en]

To ascertain the clinical implications of high hyperdiploid (HH; 49-65 chromosomes) and triploid/tetraploid (TT; >65 chromosomes) adult acute myeloid leukemia (AML), all such cases were retrieved from the Swedish AML Registry. Of the 3,654 cytogenetically informative cases diagnosed between January 1997 and May 2014, 68 (1.9%) were HH (n=50)/TT (n=18). Patients with HH/TT were older than those with intermediate risk (IR) AML (median 71 years vs. 67 years; P=0.042) and less often had de novo AML (63% vs. 79%; P=0.004); no such differences were observed between HH/TT and complex karyotype (CK) AML. The overall survival (OS) was similar between patients with HH/TT and CK AML (median 0.9 years vs. 0.6 years; P=0.082), whereas OS was significantly longer (median 1.6 years; P=0.028) for IR AML. The OS was shorter for cases with HH than with TT (median 0.6 years vs. 1.4 years; P=0.032) and for HH/TT AMLs with adverse abnormalities (median 0.8 years vs. 1.1 years; P=0.044). In conclusion, HH/TT AML is associated with a poor outcome, but chromosome numbers >65 and absence of adverse aberrations seem to translate into a more favorable prognosis. Thus, HH/TT AMLs are clinically heterogeneous and should not automatically be grouped as high risk.

National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-109437 (URN)10.1002/ajh.24091 (DOI)000360218000023 ()26088289 (PubMedID)
Available from: 2015-10-12 Created: 2015-09-28 Last updated: 2018-06-07Bibliographically approved
Lazarevic, V., Horstedt, A.-S., Johansson, B., Antunovic, P., Billstrom, R., Derolf, A., . . . Juliusson, G. (2014). Incidence and prognostic significance of karyotypic subgroups in older patients with acute myeloid leukemia: the Swedish population-based experience. Blood Cancer Journal, 4, e188
Open this publication in new window or tab >>Incidence and prognostic significance of karyotypic subgroups in older patients with acute myeloid leukemia: the Swedish population-based experience
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2014 (English)In: Blood Cancer Journal, ISSN 2044-5385, E-ISSN 2044-5385, Vol. 4, p. e188-Article in journal (Refereed) Published
Abstract [en]

The Swedish population-based acute myeloid leukemia registry contains data from 3251 patients (excluding acute promyelocytic leukemia) diagnosed between 1997 and 2006. Informative cytogenetic data from 1893 patients were retrospectively added, including 1054 patients aged between 60 and 79 years. Clonal abnormalities were found in 57% of the informative karyotypes. Karyotypic patterns differed by age: t(8; 21), inv(16) and t(11q23) were more common in younger patients, whereas loss of 5q, 7q and 17p, monosomal karyotype (MK) and complex karyotypes were more common in older patients. Loss of 5q, 7q and 17p often occurred together within MK. Patients with >= 5 chromosome abnormalities had worse overall survival than those with fewer abnormalities or normal karyotype in all age groups. Loss of 5q, 7q and/or 17p had, in contrast to MK, a further negative impact on survival. Multivariable Cox regression analyses on risk factors in patients <80 years with cytogenetic abnormalities and intensive treatment revealed that age and performance status had the most significant impact on survival (both P<0.001), followed by sex (P = 0.0135) and a karyotype including - 7/del(7q) (P = 0.048).

Place, publisher, year, edition, pages
London: Nature Publishing Group, 2014
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-87882 (URN)10.1038/bcj.2014.10 (DOI)000332631700008 ()
Available from: 2014-04-14 Created: 2014-04-14 Last updated: 2018-06-08Bibliographically approved
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