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  • 1.
    Andersson, Charlotta
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Li, Xingru
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Lorenz, Fryderyk
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Golovleva, Irina
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Wahlin, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Li, Aihong
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Reduction in WT1 Gene Expression During Early Treatment Predicts the Outcome in Patients With Acute Myeloid Leukemia2012In: Diagnostic molecular pathology (Print), ISSN 1052-9551, E-ISSN 1533-4066, Vol. 21, no 4, p. 225-233Article in journal (Refereed)
    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.

  • 2. Berggren, D. Moreno
    et al.
    Folkvaljon, Y.
    Engvall, M.
    Sundberg, J.
    Lehman, S.
    Lambe, M.
    Antunovic, P.
    Garelius, H.
    Hellstrom-Lindberg, E.
    Jadersten, M.
    Lorenz, Fryderyk
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Nilsson, L.
    Ejerblad, E.
    VALIDATION OF PROGNOSTIC SCORING SYSTEMS FOR MYELODYSPLASTIC SYNDROMES IN THE SWEDISH MDS-REGISTER2016In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 101, p. 243-243Article in journal (Other academic)
  • 3.
    Lorenz, Fryderyk
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Pawlowicz, E.
    Bjorkvall, C. Kampe
    Brustad, A. Bulanda
    Machaczka, M.
    HYPERFERRITINEMIA AND SERUM INFLAMMATORY CYTOKINES IN ADULTS WITH GAUCHER DISEASE TYPE 12016In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 101, no S1, p. 580-581, article id E1403Article in journal (Other academic)
  • 4.
    Lorenz, Fryderyk
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Pawlowicz, Ewa
    Klimkowska, Monika
    Beshara, Soheir
    Brustad, Agnes Bulanda
    Skotnicki, Aleksander B.
    Wahlin, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Machaczka, Maciej
    Ferritinemia and serum inflammatory cytokines in Swedish adults with Gaucher disease type 12018In: Blood Cells, Molecules & Diseases, ISSN 1079-9796, E-ISSN 1096-0961, Vol. 68, p. 35-42Article in journal (Refereed)
    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. 

  • 5. Machaczka, M.
    et al.
    Lorenz, Fryderyk
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Pawlowicz, E.
    Gajewski, M.
    Wolan, M.
    Klimkowska, M.
    Hyperferritinemia and serum inflammatory cytokines in 71 adults with newly diagnosed hemophagocytic lymphohistiocytosis associated with hematological malignancy2017In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 102, p. 761-761Article in journal (Other academic)
  • 6. Machaczka, Maciej
    et al.
    Lorenz, Fryderyk
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Kleinotiene, Grazina
    Bulanda, Agnieszka
    Markuszewska-Kuczynska, Alicja
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Hematology Center Karolinska, Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Raistenskis, Juozas
    Klimkowska, Monika
    Recurrent pulmonary aspergillosis and mycobacterial infection in an unsplenectomized patient with type 1 Gaucher disease2014In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 119, no 1, p. 44-49Article in journal (Refereed)
    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.

  • 7. Svensson, Tobias
    et al.
    Chowdhury, Onima
    Garelius, Hege
    Lorenz, Fryderyk
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Saft, Leonie
    Jacobsen, Sten-Eirik
    Hellström-Lindberg, Eva
    Cherif, Honar
    A pilot phase I dose finding safety study of the thrombopoietin-receptor agonist, eltrombopag, in patients with myelodysplastic syndrome treated with azacitidine2014In: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 93, no 5, p. 439-445Article in journal (Refereed)
    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.

  • 8.
    Wahlin, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Lorenz, Fryderyk
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Fredriksson, Maritha
    Department of Hematology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Remberger, Mats
    Centre of Allogeneic Stem Cell Transplantation at Huddinge, Karolinska Institutet, Stockholm, Sweden.
    Wahlin, Björn E
    Department of Hematology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Hägglund, Hans
    Department of Hematology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    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.2011In: Medical Oncology, ISSN 1357-0560, E-ISSN 1559-131X, Vol. 28, no 2, p. 552-558Article in journal (Refereed)
    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.

1 - 8 of 8
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