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  • 1. 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)
  • 2. Blink, Marjolein
    et al.
    Zimmermann, Martin
    von Neuhoff, Christine
    Reinhardt, Dirk
    de Haas, Valerie
    Hasle, Henrik
    O'Brien, Maureen M
    Stark, Batia
    Tandonnet, Julie
    Pession, Andrea
    Tousovska, Katerina
    Cheuk, Daniel K L
    Kudo, Kazuko
    Taga, Takashi
    Rubnitz, Jeffrey E
    Haltrich, Iren
    Balwierz, Walentyna
    Pieters, Rob
    Forestier, Erik
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Johansson, Bertil
    van den Heuvel-Eibrink, Marry M
    Zwaan, C Michel
    Normal karyotype is a poor prognostic factor in myeloid leukemia of Down syndrome: a retrospective, international study2014In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 99, no 2, p. 299-307Article in journal (Refereed)
    Abstract [en]

    Myeloid leukemia of Down syndrome has a better prognosis than sporadic pediatric acute myeloid leukemia. Most cases of myeloid leukemia of Down syndrome are characterized by additional cytogenetic changes besides the constitutional trisomy 21, but their potential prognostic impact is not known. We, therefore, conducted an international retrospective study of clinical characteristics, cytogenetics, treatment, and outcome of 451 children with myeloid leukemia of Down syndrome. All karyotypes were centrally reviewed before assigning patients to subgroups. The overall 7-year event-free survival for the entire cohort was 78% (± 2%), with the overall survival rate being 79% (± 2%), the cumulative incidence of relapse 12% (± 2%), and the cumulative incidence of toxic death 7% (± 1%). Outcome estimates showed large differences across the different cytogenetic subgroups. Based on the cumulative incidence of relapse, we could risk-stratify patients into two groups: cases with a normal karyotype (n=103) with a higher cumulative incidence of relapse (21%± 4%) than cases with an aberrant karyotype (n=255) with a cumulative incidence of relapse of 9% (± 2%) (P=0.004). Multivariate analyses revealed that white blood cell count ≥ 20 × 10(9)/L and age >3 years were independent predictors for poor event-free survival, while normal karyotype independently predicted inferior overall survival, event-free survival, and relapse-free survival. In conclusion, this study showed large differences in outcome within patients with myeloid leukemia of Down syndrome and identified novel prognostic groups that predicted clinical outcome and hence may be used for stratification in future treatment protocols.

  • 3. Ghez, D.
    et al.
    Fortpied, C.
    Mounier, N.
    Carde, P.
    Perrot, A.
    Khaled, H.
    Amorim, S.
    Ramadan, S.
    Le Bras, F.
    Erlanson, Martin
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Herbaux, C.
    Marolleau, J. P.
    Nicolas-Virelizier, E.
    Casasnovas, O.
    Stamatoullas-Bastard, A.
    Ferme, C.
    STEM CELL COLLECTION AFTER FAILURE OF UPFRONT ABVD OR BEACOPP IN PATIENTS WITH HIGH RISK ADVANCED STAGE III-IV HODGKIN'S LYMPHOMA2016In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 101, no S5, p. 50-50, article id P091Article in journal (Refereed)
  • 4. Jonsdottir, Gudbjörg
    et al.
    Lund, Sigrún H.
    Björkholm, Magnus
    Turesson, Ingemar
    Wahlin, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Mailankody, Sham
    Blimark, Cecilie
    Hultcrantz, Malin
    Porwit, Anna
    Landgren, Ola
    Kristinsson, Sigurdur Y.
    Survival in multiple myeloma patients who develop second malignancies: a population-based cohort study2016In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 101, no 4, p. e145-e148Article in journal (Refereed)
  • 5. Kozlowski, Piotr
    et al.
    Åström, Maria
    Ahlberg, Lucia
    Bernell, Per
    Hulegårdh, Erik
    Hägglund, Hans
    Karlsson, Karin
    Markuszewska-Kuczynska, Alicja
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Tomaszewska-Toporska, Beata
    Smedmyr, Bengt
    Hallbook, Helene
    High curability via intensive reinduction chemotherapy and stem cell transplantation in young adults with relapsed acute lymphoblastic leukemia in Sweden 2003-20072012In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 97, no 9, p. 1414-1421Article in journal (Refereed)
    Abstract [en]

    Background A minority of patients with adult acute lymphoblastic leukemia who relapse are rescued. The aim of this population-based study was to assess the results of reinduction treatment and allogeneic stem cell transplantation in patients in second complete remission.

    Design and Methods Between 2003-2007, 76 adults (<66 years) with relapsed acute lymphoblastic leukemia (Burkitt's leukemia excluded) were prospectively reported to The Swedish Adult Acute Leukemia Registry and later evaluated.

    Results Reinduction with: (i) mitoxantrone, etoposide, and cytarabine (MEA); (ii) fludarabine, cytarabine, pegylated-asparaginase plus granulocyte colony-stimulating factor (FLAG-Asp); and (iii) cytarabine, betamethasone, cyclophosphamide, daunorubicin, and vincristine (ABCDV) resulted in complete remission in 6/9 (67%), 10/16 (63%) and 9/21 (43%) of the patients, respectively. Allogeneic stem cell transplantation was performed during second complete remission in 29 patients. Multivariate analysis regarding overall survival after relapse revealed that age over 35 years at diagnosis and relapse within 18 months were negative prognostic factors. Overall survival rates at 3 and 5 years were 22% (95% CI: 13-32) and 15% (95% CI: 7-24). Of 19 patients less than 35 years at diagnosis who underwent allogeneic stem cell transplantation in second remission, ten (53%) are still alive at a median of 5.5 years (range, 4.2-8.3) after relapse, whereas all patients over 35 years old at diagnosis have died.

    Conclusions Allogeneic stem cell transplantation remains the treatment of choice for young adults with relapsed acute lymphoblastic leukemia. Both (i) mitoxantrone, etoposide, and cytarabine and (ii) fludarabine, cytarabine, pegylated-asparaginase plus granulocyte colony-stimulating factor seem effective as reinduction treatments and should be further evaluated. New salvage strategies are needed, especially for patients over 35 years old at diagnosis.

  • 6. Kristinsson, Sigurdur Y
    et al.
    Björkholm, Magnus
    Andersson, Therese M-L
    Eloranta, Sandra
    Dickman, Paul W
    Goldin, Lynn R
    Blimark, Cecilie
    Mellqvist, Ulf-Henrik
    Wahlin, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Turesson, Ingemar
    Landgren, Ola
    Patterns of survival and causes of death following a diagnosis of monoclonal gammopathy of undetermined significance. A population-based study.2009In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 94, no 12, p. 1714-1720Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: There are limited data on survival patterns among patients with monoclonal gammopathy of undetermined significance. DESIGN AND METHODS: We compared the survival of 4,259 patients with monoclonal gammopathy of undetermined significance, collected from hematology outpatient units in Sweden, with the survival of the general population by computing relative survival ratios. We also compared causes of death in these patients with those in 16,151 matched controls. RESULTS: One-, 5-, 10-, and 15-year relative survival ratios were 0.98 (95% CI 0.97-0.99), 0.93 (0.91-0.95), 0.82 (0.79-0.84), and 0.70 (0.64-0.76), respectively. Younger age at diagnosis of the gammopathy was associated with a significantly lower excess mortality compared to that in older patients (p<0.001). The excess mortality among patients with gammopathy increased with longer follow-up (p<0.0001). IgM (versus IgG/A) gammopathy was associated with a superior survival (p=0.038). Patients with monoclonal gammopathy of undetermined significance had an increased risk of dying from multiple myeloma (hazards ratio (HR)=553; 95% CI 77-3946), Waldenström's macroglobulinemia (HR=infinity), other lymphoproliferative malignancies (6.5; 2.8-15.1), other hematologic malignancies (22.9; 8.9-58.7), amyloidosis (HR=infinity), bacterial infections (3.4; 1.7-6.7), ischemic heart disease (1.3; 1.1-1.4), other heart disorders (1.5; 1.2-1.8), other hematologic conditions (6.9; 2.7-18), liver (2.1; 1.1-4.2), and renal diseases (3.2; 2.0-4.9). CONCLUSIONS: Our finding of decreased life expectancy in patients with monoclonal gammopathy of undetermined significance, which was most pronounced in the elderly and explained by both malignant transformation and non-malignant causes, is of importance in the understanding and clinical management of this disease. The underlying mechanisms may be causally related to the gammopathy, but may also be explained by underlying disease that led to the detection of the hematologic disease. Our results are of importance since they give a true estimation of survival in patients with monoclonal gammopathy of undetermined significance diagnosed in clinical practice.

  • 7. Kristinsson, Sigurdur Y
    et al.
    Tang, Min
    Pfeiffer, Ruth M
    Björkholm, Magnus
    Goldin, Lynn R
    Blimark, Cecilie
    Mellqvist, Ulf-Henrik
    Wahlin, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Turesson, Ingemar
    Landgren, Ola
    Monoclonal gammopathy of undetermined significance and risk of infections: a population-based study.2012In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 97, no 6, p. 854-858Article in journal (Refereed)
    Abstract [en]

    No comprehensive evaluation has been conducted to assess the risk of viral and bacterial infections among patients with monoclonal gammopathy of undetermined significance. Using population-based data from Sweden, we estimated risk of infections among 5,326 MGUS patients compared to 20,161 matched controls. Patients with monoclonal gammopathy of undetermined significance had a 2-fold increased risk (P<0.05) of developing any infection at 5 and 10 years of follow-up. More specifically, patients with monoclonal gammopathy of undetermined significance had an increased risk (P<0.05) of bacterial infections (pneumonia, osteomyelitis, septicemia, pyelonephritis, cellulitis, endocarditis, and meningitis), and viral infections (influenza and herpes zoster). Patients with monoclonal gammopathy of undetermined significance with M-protein concentrations >2.5 g/dL at diagnosis had highest risks of infections; however, the risk was also increased (P<0.05) among those with concentrations <0.5 g/dL. Patients with monoclonal gammopathy of undetermined significance who developed infections had no excess risk of developing multiple myeloma. Our findings provide novel clues for the mechanisms behind infections in patients with plasma cell dyscrasias, and may have clinical implications.

  • 8.
    Liljeholm, Maria
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Vikberg, Ann-Louise
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    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.
    Congenital dyserythropoietic anemia type III and primary hemochromatosis; coexistence of mutations in KIF23 and HFE2015In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 100, p. 594-594Article in journal (Other academic)
  • 9.
    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)
  • 10. 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)
  • 11. Marincevic-Zuniga, Yanara
    et al.
    Zachariadis, Vasilios
    Cavelier, Lucia
    Castor, Anders
    Barbany, Gisela
    Forestier, Erik
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Fogelstrand, Linda
    Heyman, Mats
    Abrahamsson, Jonas
    Lonnerholm, Gudmar
    Nordgren, Ann
    Syvanen, Ann-Christine
    Nordlund, Jessica
    PAX5-ESRRB is a recurrent fusion gene in B-cell precursor pediatric acute lymphoblastic leukemia2016In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 101, no 1, p. E20-E23Article in journal (Refereed)
  • 12. Nahi, Hareth
    et al.
    Hägglund, Hans
    Ahlgren, Thomas
    Bernell, Per
    Hardling, Mats
    Karlsson, Karin
    Lazarevic, Vladimir Lj
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Linderholm, Mats
    Smedmyr, Bengt
    Åström, Maria
    Hallböök, Helene
    An investigation into whether deletions in 9p reflect prognosis in adult precursor B-cell acute lymphoblastic leukemia: a multi-center study of 381 patients2008In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 93, no 11, p. 1734-1738Article in journal (Refereed)
    Abstract [en]

    In acute lymphoblastic leukemia, besides age and white cell count at diagnosis, the cytogenetic abnormalities t(9;22)/BCR-ABL and t(4;11)/MLL-AF4 are important prognostic markers and are often included in the treatment stratification of patients with adult acute lymphoblastic leukemia. Deletions in 9p are seen in about 9% of cases of adult acute lymphoblastic leukemia, but their prognostic impact has been controversial. Cytogenetic data from 381 patients diagnosed with B-precursor acute lymphoblastic leukemia were reviewed. Chromosomal analysis was successful in 240 cases. Of these cases, 18 (8%) had abnormalities in 9p and they were compared with patients with normal karyotypes and patients with t(9;22)/BCR-ABL. Patients with abnormalities of chromosome 9 showed significantly shorter overall survival compared with patients with normal karyotypes. In fact, overall survival was similar to that in the poor prognosis t(9;22)/BCR-ABL-positive group. Our data suggest that chromosomal abnormalities involving 9p may have a significant negative impact on survival in adult B-precursor acute lymphoblastic leukemia.

  • 13. Oskarsson, Trausti
    et al.
    Soderhall, Stefan
    Arvidson, Johan
    Forestier, Erik
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Montgomery, Scott
    Bottai, Matteo
    Lausen, Birgitte
    Carlsen, Niels
    Hellebostad, Marit
    Lahteenmaki, Paivi
    Saarinen-Pihkala, Ulla M.
    Jonsson, Olafur G.
    Heyman, Mats
    Relapsed childhood acute lymphoblastic leukemia in the Nordic countries: prognostic factors, treatment and outcome2016In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 101, no 1, p. 68-76Article in journal (Refereed)
    Abstract [en]

    Relapse is the main reason for treatment failure in childhood acute lymphoblastic leukemia. Despite improvements in the up-front therapy, survival after relapse is still relatively poor, especially for high-risk relapses. The aims of this study were to assess outcomes following acute lymphoblastic leukemia relapse after common initial Nordic Society of Paediatric Haematology and Oncology protocol treatment; to validate currently used risk stratifications, and identify additional prognostic factors for overall survival. Altogether, 516 of 2735 patients (18.9%) relapsed between 1992 and 2011 and were included in the study. There were no statistically significant differences in outcome between the up-front protocols or between the relapse protocols used, but an improvement over time was observed. The 5-year overall survival for patients relapsing in the period 2002-2011 was 57.5 +/- 3.4%, but 44.7 +/- 3.2% (P<0.001) if relapse occurred in the period 1992-2001. Factors independently predicting mortality after relapse included short duration of first remission, bone marrow involvement, age ten years or over, unfavorable cytogenetics, and Down syndrome. T-cell immunophenotype was not an independent prognostic factor unless in combination with hyperleukocytosis at diagnosis. The outcome for early combined pre-B relapses was unexpectedly poor (5-year overall survival 38.0 +/- 10.6%), which supports the notion that these patients need further risk adjustment. Although survival outcomes have improved over time, the development of novel approaches is urgently needed to increase survival in relapsed childhood acute lymphoblastic leukemia.

  • 14. Paulsson, Kajsa
    et al.
    Forestier, Erik
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Andersen, Mette K
    Autio, Kirsi
    Barbany, Gisela
    Borgström, Georg
    Cavelier, Lucia
    Golovleva, Irina
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Heim, Sverre
    Heinonen, Kristiina
    Hovland, Randi
    Johannsson, Johann H
    Kjeldsen, Eigil
    Nordgren, Ann
    Palmqvist, Lars
    Johansson, Bertil
    High modal number and triple trisomies are highly correlated favorable factors in childhood B-cell precursor high hyperdiploid acute lymphoblastic leukemia treated according to the NOPHO ALL 1992/2000 protocols2013In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 98, no 9, p. 1424-1432Article in journal (Refereed)
    Abstract [en]

    Between 1992 and 2008, 713 high hyperdiploid acute lymphoblastic leukemias in children aged 1-15 years were diagnosed and treated according to the Nordic Society for Pediatric Hematology and Oncology acute lymphoblastic leukemia 1992/2000 protocols. Twenty (2.8%) harbored t(1;19), t(9;22), der(11q23), or t(12;21). The median age of patients with "classic" high hyperdiploidy was lower than that of patients with translocation-positive high hyperdiploidy (P<0.001). Cases with triple trisomies (+4, +10, +17), comprising 50%, had higher modal numbers than the triple trisomy-negative cases (P<0.0001). The probabilities of event-free survival and overall survival were lower for those with white blood cell counts ≥ 50 × 10(9)/L (P=0.017/P=0.009), ≥ 5% bone marrow blasts at day 29 (P=0.001/0.002), and for high-risk patients (P<0.001/P=0.003), whereas event-free, but not overall, survival, was higher for cases with gains of chromosomes 4 (P<0.0001), 6 (P<0.003), 17 (P=0.010), 18 (P=0.049), and 22 (P=0.040), triple trisomies (P=0.002), and modal numbers >53/55 (P=0.020/0.024). In multivariate analyses, modal number and triple trisomies were significantly associated with superior event-free survival in separate analyses with age and white blood cell counts. When including both modal numbers and triple trisomies, only low white blood cell counts were significantly associated with superior event-free survival (P=0.009). We conclude that high modal chromosome numbers and triple trisomies are highly correlated prognostic factors and that these two parameters identify the same subgroup of patients characterized by a particularly favorable outcome.

  • 15. Reimer, Jana
    et al.
    Knoess, Sabine
    Labuhn, Maurice
    Charpentier, Emmanuelle M.
    Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Max Planck Institute for Infection Biology, Berlin, Germany.
    Goehring, Gudrun
    Schlegelberger, Brigitte
    Klusmann, Jan-Henning
    Heckl, Dirk
    CRISPR-Cas9-induced t(11;19)/MLL-ENL translocations initiate leukemia in human hematopoietic progenitor cells in vivo2017In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 102, no 9, p. 1558-1566Article in journal (Refereed)
    Abstract [en]

    Chromosomal translocations that generate oncogenic fusion proteins are causative for most pediatric leukemias and frequently affect the MLL/ KMT2A gene. In vivo modeling of bona fide chromosomal translocations in human hematopoietic stem and progenitor cells is challenging but essential to determine their actual leukemogenic potential. We therefore developed an advanced lentiviral CRISPR-Cas9 vector that efficiently transduced human CD34(+) hematopoietic stem and progenitor cells and induced the t(11; 19)/MLL-ENL translocation. Leveraging this system, we could demonstrate that hematopoietic stem and progenitor cells harboring the translocation showed only a transient clonal growth advantage in vitro. In contrast, t(11; 19)/MLL-ENL-harboring CD34(+) hematopoietic stem and progenitor cells not only showed longterm engraftment in primary immunodeficient recipients, but t(11; 19)/ MLL-ENL also served as a first hit to initiate a monocytic leukemia-like disease. Interestingly, secondary recipients developed acute lymphoblastic leukemia with incomplete penetrance. These findings indicate that environmental cues not only contribute to the disease phenotype, but also to t(11; 19)/ MLL-ENL-mediated oncogenic transformation itself. Thus, by investigating the true chromosomal t(11; 19) rearrangement in its natural genomic context, our study emphasizes the importance of environmental cues for the pathogenesis of pediatric leukemias, opening an avenue for novel treatment options.

  • 16.
    Richter, Karin
    et al.
    Umeå University, Faculty of Medicine, Umeå Centre for Molecular Medicine (UCMM).
    Pinto do O, Perpetua
    Hägglund, Anna-Carin
    Wahlin, Anders
    Carlsson, Leif
    Lhx2 expression in hematopoietic progenitor/stem cells in vivo causes a chronic myeloproliferative disorder and altered globin expression.2003In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 88, no 12, p. 1336-1347Article in journal (Refereed)
  • 17. Sandahl, Julie Damgaard
    et al.
    Coenen, Eva A.
    Forestier, Erik
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Harbott, Jochen
    Johansson, Bertil
    Kerndrup, Gitte
    Adachi, Souichi
    Auvrignon, Anne
    Beverloo, H. Berna
    Cayuela, Jean-Michel
    Chilton, Lucy
    Fornerod, Maarten
    de Haas, Valerie
    Harrison, Christine J.
    Inaba, Hiroto
    Kaspers, Gertjan J. L.
    Liang, Der-Cherng
    Locatelli, Franco
    Masetti, Riccardo
    Perot, Christine
    Raimondi, Susana C.
    Reinhardt, Katarina
    Tomizawa, Daisuke
    von Neuhoff, Nils
    Zecca, Marco
    Zwaan, C. Michel
    van den Heuvel-Eibrink, Marry M.
    Hasle, Henrik
    t(6;9)(p22; q34)/DEK-NUP214-rearranged pediatric myeloid leukemia: an international study of 62 patients2014In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 99, no 5, p. 865-872Article in journal (Refereed)
    Abstract [en]

    Acute myeloid leukemia with t(6; 9)(p22; q34) is listed as a distinct entity in the 2008 World Health Organization classification, but little is known about the clinical implications of t(6; 9)-positive myeloid leukemia in children. This international multicenter study presents the clinical and genetic characteristics of 62 pediatric patients with t(6; 9)/DEKNUP214-rearranged myeloid leukemia; 54 diagnosed as having acute myeloid leukemia, representing <1% of all childhood acute myeloid leukemia, and eight as having myelodysplastic syndrome. The t(6; 9)/DEK-NUP214 was associated with relatively late onset (median age 10.4 years), male predominance (sex ratio 1.7), French-American-British M2 classification (54%), myelodysplasia (100%), and FLT3-ITD (42%). Outcome was substantially better than previously reported with a 5-year event-free survival of 32%, 5-year overall survival of 53%, and a 5-year cumulative incidence of relapse of 57%. Hematopoietic stem cell transplantation in first complete remission improved the 5-year event-free survival compared with chemotherapy alone (68% versus 18%; P<0.01) but not the overall survival (68% versus 54%; P=0.48). The presence of FLT3-ITD had a non-significant negative effect on 5-year overall survival compared with non-mutated cases (22% versus 62%; P=0.13). Gene expression profiling showed a unique signature characterized by significantly higher expression of EYA3, SESN1, PRDM2/RIZ, and HIST2H4 genes. In conclusion, t(6; 9)/DEK-NUP214 represents a unique subtype of acute myeloid leukemia with a high risk of relapse, high frequency of FLT3-ITD, and a specific gene expression signature.

  • 18.
    Sandström, Herbert
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Wahlin, A
    Congenital dyserythropoietic anemia type III.2000In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 85, no 7, p. 753-7Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND OBJECTIVES: Congenital dyserythropoietic anemia type III (CDA-III) is a group of very rare disorders characterized by similar bone marrow morphology. The clinical picture is characterized by hemolytic anemia and dramatic bone marrow changes dominated by active erythropoiesis with big multinucleated erythroblasts. The aim of this review is to describe the clinical manifestations, laboratory findings, and management CDA-III.

    EVIDENCE AND INFORMATION SOURCES: The present review critically examines relevant articles and abstracts published in journals covered by the Science Citation Index and Medline. The authors have performed several studies on CDA-III.

    STATE OF ART AND PERSPECTIVES: The clinical and laboratory manifestations of CDA-III indicate that the gene responsible for it, which has been mapped to chromosome 15q22, is expressed not only in erythroblasts during mitosis but also in B-cells, and in cells of the retina. Preliminary results indicate genetic and phenotypic similarities between a Swedish and an American family, both with an autosomally dominant inherited form of CDA-III. It is possible that the genetic lesion is identical in these families, but the different phenotypes and modes of inheritance reported among some other cases of CDA-III are probably the results of other genetic lesions. At present, the function of the gene responsible for the Swedish (V sterbotten) variant of CDA-III (CDAN3) is unknown and it is an important goal to characterize and clone this gene in order to study its function.

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    Progression of chronic phase chronic myeloid leukemia to advanced phase on tki therapy: A population based analysis from the Swedish CML register2015In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 100, p. 233-233Article in journal (Other academic)
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    ADULTS AND CHILDREN (1-45 YEARS) WITH PH-NEGATIVE ALL HAVE ALMOST IDENTICAL OUTCOME IN RISK-STRATIFIED ANALYSIS OF NOPHO ALL20082016In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 101, p. 35-35Article in journal (Other academic)
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    DEVELOPMENT OF A PROGRESS TEST BASED ON THE EHA CURRICULUM AND EHA CV PASSPORT, USED FOR YEARLY EVALUATION OF HEMATOLOGY RESIDENCY IN SWEDEN2015In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 100, p. 776-776Article in journal (Other academic)
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    HODGKIN LYMPHOMA IN SWEDEN SINCE 2000: BETTER SURVIVAL ONLY IN ELDERLY WOMEN - A SWEDISH LYMPHOMA REGISTRY STUDY2016In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 101, no S5, p. 22-22, article id P005Article in journal (Refereed)
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    MODULATION OF LEUKOTRIENE SIGNALING INHIBITING CELL GROWTH IN CHRONIC MYELOID LEUKEMIA2016In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 101, p. 731-731Article in journal (Other academic)
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