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Lorenz, Fryderyk
Publications (10 of 10) Show all publications
Lorenz, F., Klimkowska, M., Pawłowicz, E., Brustad, A. B., Erlanson, M. & Machaczka, M. (2018). Clinical characteristics, therapy response, and outcome of 51 adult patients with hematological malignancy-associated hemophagocytic lymphohistiocytosis: a single institution experience. Leukemia and Lymphoma, 59(8), 1840-1850
Open this publication in new window or tab >>Clinical characteristics, therapy response, and outcome of 51 adult patients with hematological malignancy-associated hemophagocytic lymphohistiocytosis: a single institution experience
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2018 (English)In: Leukemia and Lymphoma, ISSN 1042-8194, E-ISSN 1029-2403, Vol. 59, no 8, p. 1840-1850Article in journal (Refereed) Published
Abstract [en]

Hemophagocytic lymphohistiocytosis (HLH) is an underdiagnosed but life-threatening syndrome of hyperinflammation often occurring in adults with hematological malignancies (hM-HLH). The aim of the study was to describe clinical characteristics, therapy response, and outcome of adults with hM-HLH. The study included 51 adults with hM-HLH aged 23–84 years. Hyperferritinemia ≥500 µg/L was present in 96% of patients. The serum concentration of sIL-2Rα ≥ 2400 U/mL was revealed in 94% of patients. Twenty-three patients (45%) responded to therapy and achieved remission of HLH. The probability of overall survival (OS) at 6, 12, 24, and 60 months after HLH diagnosis were 42, 20, 15, and 15%, respectively. Patients with HLH during chemotherapy showed longer OS (median 124 days) than the patients who had HLH solely attributed to malignancy (median 65 days), but this difference was not statistically significant. Awareness of HLH in lymphoid and myeloid malignancies is crucial for improved survival.

Place, publisher, year, edition, pages
Taylor & Francis, 2018
Keywords
Hemophagocytic lymphohistiocytosis, hemophagocytic syndrome, hyperferritinemia, cytokines, hematological malignancy, survival
National Category
Hematology
Identifiers
urn:nbn:se:umu:diva-151198 (URN)10.1080/10428194.2017.1403018 (DOI)000437352000009 ()29295642 (PubMedID)2-s2.0-85039858583 (Scopus ID)
Available from: 2018-09-05 Created: 2018-09-05 Last updated: 2018-09-05Bibliographically 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
Berggren, D. M., Folkvaljon, Y., Engvall, M., Sundberg, J., Lambe, M., Antunovic, P., . . . Ejerblad, E. (2018). Prognostic scoring systems for myelodysplastic syndromes (MDS) in a population-based setting: a report from the Swedish MDS register. British Journal of Haematology, 181(5), 614-627
Open this publication in new window or tab >>Prognostic scoring systems for myelodysplastic syndromes (MDS) in a population-based setting: a report from the Swedish MDS register
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2018 (English)In: British Journal of Haematology, ISSN 0007-1048, E-ISSN 1365-2141, Vol. 181, no 5, p. 614-627Article in journal (Refereed) Published
Abstract [en]

The myelodysplastic syndromes (MDS) have highly variable outcomes and prognostic scoring systems are important tools for risk assessment and to guide therapeutic decisions. However, few population-based studies have compared the value of the different scoring systems. With data from the nationwide Swedish population-based MDS register we validated the International Prognostic Scoring System (IPSS), revised IPSS (IPSS-R) and the World Health Organization (WHO) Classification-based Prognostic Scoring System (WPSS). We also present population-based data on incidence, clinical characteristics including detailed cytogenetics and outcome from the register. The study encompassed 1329 patients reported to the register between 2009 and 2013, 14% of these had therapy-related MDS (t-MDS). Based on the MDS register, the yearly crude incidence of MDS in Sweden was 2.9 per 100000 inhabitants. IPSS-R had a significantly better prognostic power than IPSS (P < 0001). There was a trend for better prognostic power of IPSS-R compared to WPSS (P=0.05) and for WPSS compared to IPSS (P=0.07). IPSS-R was superior to both IPSS and WPSS for patients aged <= 70years. Patients with t-MDS had a worse outcome compared to de novo MDS (d-MDS), however, the validity of the prognostic scoring systems was comparable for d-MDS and t-MDS. In conclusion, population-based studies are important to validate prognostic scores in a real-world' setting. In our nationwide cohort, the IPSS-R showed the best predictive power.

Keywords
myelodysplastic syndrome, International Prognostic Scoring System, revised International Prognostic Scoring System, WHO Classification-based Prognostic Scoring System, therapy-related myelodysplastic syndrome
National Category
Hematology
Identifiers
urn:nbn:se:umu:diva-150884 (URN)10.1111/bjh.15243 (DOI)000433333100007 ()29707769 (PubMedID)2-s2.0-85046032311 (Scopus ID)
Available from: 2018-08-31 Created: 2018-08-31 Last updated: 2019-05-10Bibliographically approved
Machaczka, M., Lorenz, F., Pawlowicz, E., Gajewski, M., Wolan, M. & Klimkowska, M. (2017). Hyperferritinemia and serum inflammatory cytokines in 71 adults with newly diagnosed hemophagocytic lymphohistiocytosis associated with hematological malignancy. Paper presented at 22nd Congress of the European-Hematology-Association, JUN 22-25, 2017, Madrid, SPAIN. Haematologica, 102, 761-761
Open this publication in new window or tab >>Hyperferritinemia and serum inflammatory cytokines in 71 adults with newly diagnosed hemophagocytic lymphohistiocytosis associated with hematological malignancy
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2017 (English)In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 102, p. 761-761Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
Ferrata Storti Foundation, 2017
National Category
Hematology
Identifiers
urn:nbn:se:umu:diva-137800 (URN)000404127006005 ()
Conference
22nd Congress of the European-Hematology-Association, JUN 22-25, 2017, Madrid, SPAIN
Note

Supplement: 2

Meeting Abstract: PB1905

Available from: 2017-07-27 Created: 2017-07-27 Last updated: 2018-06-09Bibliographically approved
Lorenz, F., Pawlowicz, E., Bjorkvall, C. K., Brustad, A. B. & Machaczka, M. (2016). HYPERFERRITINEMIA AND SERUM INFLAMMATORY CYTOKINES IN ADULTS WITH GAUCHER DISEASE TYPE 1. Paper presented at 21st Congress of the European-Hematology-Association, JUN 09-12, 2016, Copenhagen, DENMARK. Haematologica, 101(S1), 580-581, Article ID E1403.
Open this publication in new window or tab >>HYPERFERRITINEMIA AND SERUM INFLAMMATORY CYTOKINES IN ADULTS WITH GAUCHER DISEASE TYPE 1
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2016 (English)In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 101, no S1, p. 580-581, article id E1403Article in journal, Meeting abstract (Other academic) Published
National Category
Hematology
Identifiers
urn:nbn:se:umu:diva-124689 (URN)000379484602191 ()
Conference
21st Congress of the European-Hematology-Association, JUN 09-12, 2016, Copenhagen, DENMARK
Available from: 2016-10-03 Created: 2016-08-22 Last updated: 2018-06-09Bibliographically approved
Berggren, D. M., Folkvaljon, Y., Engvall, M., Sundberg, J., Lehman, S., Lambe, M., . . . Ejerblad, E. (2016). VALIDATION OF PROGNOSTIC SCORING SYSTEMS FOR MYELODYSPLASTIC SYNDROMES IN THE SWEDISH MDS-REGISTER. Paper presented at 21st Congress of the European-Hematology-Association, JUN 09-12, 2016, Copenhagen, DENMARK. Haematologica, 101, 243-243
Open this publication in new window or tab >>VALIDATION OF PROGNOSTIC SCORING SYSTEMS FOR MYELODYSPLASTIC SYNDROMES IN THE SWEDISH MDS-REGISTER
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2016 (English)In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 101, p. 243-243Article in journal, Meeting abstract (Other academic) Published
National Category
Medical Bioscience
Identifiers
urn:nbn:se:umu:diva-124686 (URN)000379484600529 ()
Conference
21st Congress of the European-Hematology-Association, JUN 09-12, 2016, Copenhagen, DENMARK
Available from: 2017-06-22 Created: 2017-06-22 Last updated: 2018-06-09Bibliographically approved
Svensson, T., Chowdhury, O., Garelius, H., Lorenz, F., Saft, L., Jacobsen, S.-E., . . . Cherif, H. (2014). A pilot phase I dose finding safety study of the thrombopoietin-receptor agonist, eltrombopag, in patients with myelodysplastic syndrome treated with azacitidine. European Journal of Haematology, 93(5), 439-445
Open this publication in new window or tab >>A pilot phase I dose finding safety study of the thrombopoietin-receptor agonist, eltrombopag, in patients with myelodysplastic syndrome treated with azacitidine
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2014 (English)In: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 93, no 5, p. 439-445Article in journal (Refereed) Published
Abstract [en]

Objectives: Thrombocytopenia is an independent adverse prognostic factor in patients with Myelodysplastic syndromes (MDS). Azacitidine, first-line treatment for the majority of patients with higher-risk MDS, is associated with aggravated thrombocytopenia during the first cycles. Eltrombopag is a novel thrombopoietin receptor agonist, which also has been shown to inhibit proliferation of leukaemia cell lines in vitro. This phase I clinical trial was designed to explore the safety and tolerability of combining eltrombopag with azacitidine in patients with MDS. In addition, we assessed the potential effects of eltrombopag on hematopoietic stem and progenitor cells (HSPCs) from included patients.

Patients and methods: Previously untreated patients with MDS eligible for treatment with azacitidine and with a platelet count <75x10(9)/L were included. Patients received eltrombopag in dose escalation cohorts during three cycles of azacitidine.

Results: Twelve patients, with a median age of 74yr, were included. Severe adverse events included infectious complications, deep vein thrombosis and transient ischaemic attack. The maximal tolerated eltrombopag dose was 200mg qd. Complete remission or bone marrow remission was achieved in 4 of 12 patients. Platelet counts improved or remained stable in 9 of 12 patients despite azacitidine treatment. No increase in blast count, disease progression, or bone marrow fibrosis related to study medication was reported. Eltrombopag did not induce cycling of HSPCs.

Conclusion: The combination of eltrombopag with azacitidine in high-risk MDS patients is feasible and well tolerated. Improvements in platelet counts and the potential antileukaemic effect of eltrombopag should be explored in a randomised study.

Keywords
Myelodysplastic syndrome, azacitidine, eltrombopag, thrombocytopenia, thrombopoietin-receptor
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-96813 (URN)10.1111/ejh.12383 (DOI)000343970700011 ()
Available from: 2014-12-09 Created: 2014-12-03 Last updated: 2018-06-07Bibliographically approved
Machaczka, M., Lorenz, F., Kleinotiene, G., Bulanda, A., Markuszewska-Kuczynska, A., Raistenskis, J. & Klimkowska, M. (2014). Recurrent pulmonary aspergillosis and mycobacterial infection in an unsplenectomized patient with type 1 Gaucher disease. Upsala Journal of Medical Sciences, 119(1), 44-49
Open this publication in new window or tab >>Recurrent pulmonary aspergillosis and mycobacterial infection in an unsplenectomized patient with type 1 Gaucher disease
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2014 (English)In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 119, no 1, p. 44-49Article in journal (Refereed) Published
Abstract [en]

Background. The clinical presentation of Gaucher disease (GD), an inherited lysosomal storage disorder caused by the deficient activity of the lysosomal enzyme glucocerebrosidase, is highly variable, and three clinical types are distinguished based upon the presence of neurologic symptoms. Thrombocytopenia, anemia, hepatosplenomegaly, and bone manifestations are the most typical signs of GD type 1 (GD1). Case presentation. We present the case of an unsplenectomized man suffering from heterozygous GD1 with mutations of c.1226A>G (N370S) and RecNci I (L444P, A456P, and V460V) in the GBA1 gene, who developed recurrent pulmonary aspergillosis caused by Aspergillus fumigatus and a mycobacterial infection caused by Mycobacterium avium. Despite long-lasting therapy of both aspergillosis (including antifungal drugs and surgery), and the mycobacterial infection (triple therapy with rifampicin, ethambutol, and clarithromycin), recurrent positivity for M. avium and A. fumigatus was detected. Conclusions. Symptomatic lung involvement and an increased susceptibility to pulmonary infections are uncommon in GD and, if present, are often associated with more severe disease manifestations. To our knowledge, this is the first published report on the association of GD and pulmonary aspergillosis and mycobacterial infection. It illustrates the increased susceptibility of untreated GD patients to opportunistic pulmonary infections and ineffective eradication of these infections despite adequate therapy.

Place, publisher, year, edition, pages
Informa Healthcare, 2014
Keywords
Aspergillosis, Aspergillus fumigatus, Gaucher disease, mycobacterial infection, Mycobacterium avium
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-87407 (URN)10.3109/03009734.2013.857373 (DOI)000331828500007 ()
Available from: 2014-04-02 Created: 2014-03-31 Last updated: 2018-06-08Bibliographically approved
Andersson, C., Li, X., Lorenz, F., Golovleva, I., Wahlin, A. & Li, A. (2012). Reduction in WT1 Gene Expression During Early Treatment Predicts the Outcome in Patients With Acute Myeloid Leukemia. Diagnostic molecular pathology (Print), 21(4), 225-233
Open this publication in new window or tab >>Reduction in WT1 Gene Expression During Early Treatment Predicts the Outcome in Patients With Acute Myeloid Leukemia
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2012 (English)In: Diagnostic molecular pathology (Print), ISSN 1052-9551, E-ISSN 1533-4066, Vol. 21, no 4, p. 225-233Article in journal (Refereed) Published
Abstract [en]

Wilms tumor gene 1 (WT1) expression has been suggested as an applicable minimal residual disease marker in acute myeloid leukemia (AML). We evaluated the use of this marker in 43 adult AML patients. Quantitative assessment of WT1 gene transcripts was performed using real-time quantitative-polymerase chain reaction assay. Samples from both the peripheral blood and the bone marrow were analyzed at diagnosis and during follow-up. A strong correlation was observed between WT1 normalized with 2 different control genes (beta-actin and ABL1, P < 0.001). WT1 mRNA level at diagnosis was of no prognostic relevance (P > 0.05). A >= 1-log reduction in WT1 expression in bone marrow samples taken < 1 month after diagnosis significantly correlated with an improved overall survival (P = 0.004) and freedom from relapse (P = 0.010) when beta-actin was used as control gene. Furthermore, a reduction in WT1 expression by >= 2 logs in peripheral blood samples taken at a later time point significantly correlated with a better outcome for overall survival (P = 0.004) and freedom from relapse (P = 0.012). This result was achieved when normalizing against both b-actin and ABL1. These results therefore suggest that WT1 gene expression can provide useful information for minimal residual disease detection in adult AML patients and that combined use of control genes can give more informative results.

Place, publisher, year, edition, pages
Lippincott Williams & Wilkins, 2012
Keywords
WT1 gene expression, acute myeloid leukemia, minimal residual disease, RQ-PCR, control genes
National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:umu:diva-62781 (URN)10.1097/PDM.0b013e318257ddb9 (DOI)000311221400005 ()
Available from: 2013-01-02 Created: 2012-12-18 Last updated: 2018-06-08Bibliographically approved
Wahlin, A., Lorenz, F., Fredriksson, M., Remberger, M., Wahlin, B. E. & Hägglund, H. (2011). Hyperferritinemia is associated with low incidence of graft versus host disease, high relapse rate, and impaired survival in patients with blood disorders receiving allogeneic hematopoietic stem cell grafts.. Medical Oncology, 28(2), 552-558
Open this publication in new window or tab >>Hyperferritinemia is associated with low incidence of graft versus host disease, high relapse rate, and impaired survival in patients with blood disorders receiving allogeneic hematopoietic stem cell grafts.
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2011 (English)In: Medical Oncology, ISSN 1357-0560, E-ISSN 1559-131X, Vol. 28, no 2, p. 552-558Article in journal (Refereed) Published
Abstract [en]

High pre-transplantation serum ferritin levels have been reported to be associated with impaired survival post-transplantation in patients with acute myeloid leukemia or myelodysplastic syndrome. We performed a retrospective study of 309 patients who underwent allogeneic hematopoietic stem cell transplantation at two transplantation centers. The aim was to determine the effect of pre-transplantation hyperferritinemia on survival, graft versus host disease, and relapse. In both univariate and multivariate analysis, elevated ferritin levels were significantly associated with shorter overall and relapse-free survival times and increased relapse rate, but lower risk of chronic graft versus host disease. Elevated ferritin levels were not associated with non-relapse mortality. We hypothesize that ferritin may exert an immunosuppressive effect, reducing graft versus host disease and graft versus leukemia effects, resulting in increased risk of relapse and impaired survival.

Keywords
Ferritin, Graft versus host disease, Relapse, Survival, Immunosuppressive
National Category
Cancer and Oncology
Research subject
Oncology
Identifiers
urn:nbn:se:umu:diva-41026 (URN)10.1007/s12032-010-9496-1 (DOI)20393815 (PubMedID)
Available from: 2011-03-16 Created: 2011-03-16 Last updated: 2018-06-08Bibliographically approved
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