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  • 1.
    Andersson, Charlotta
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Li, Xingru
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Lorenz, Fryderyk
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Golovleva, Irina
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Medicinsk och klinisk genetik.
    Wahlin, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Li, Aihong
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Reduction in WT1 Gene Expression During Early Treatment Predicts the Outcome in Patients With Acute Myeloid Leukemia2012Ingår i: Diagnostic molecular pathology (Print), ISSN 1052-9551, E-ISSN 1533-4066, Vol. 21, nr 4, s. 225-233Artikel i tidskrift (Refereegranskat)
    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.
    Björnfot, Cecilia
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Garpebring, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Qvarlander, Sara
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Malm, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper.
    Eklund, Anders
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Wahlin, Anders
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Assessing cerebral arterial pulse wave velocity using 4D flow MRI2021Ingår i: Journal of Cerebral Blood Flow and Metabolism, ISSN 0271-678X, E-ISSN 1559-7016, Vol. 41, nr 10, s. 2769-2777Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Intracranial arterial stiffening is a potential early marker of emerging cerebrovascular dysfunction and could be mechanistically involved in disease processes detrimental to brain function via several pathways. A prominent consequence of arterial wall stiffening is the increased velocity at which the systolic pressure pulse wave propagates through the vasculature. Previous non-invasive measurements of the pulse wave propagation have been performed on the aorta or extracranial arteries with results linking increased pulse wave velocity to brain pathology. However, there is a lack of intracranial “target-organ” measurements. Here we present a 4D flow MRI method to estimate pulse wave velocity in the intracranial vascular tree. The method utilizes the full detectable branching structure of the cerebral vascular tree in an optimization framework that exploits small temporal shifts that exists between waveforms sampled at varying depths in the vasculature. The method is shown to be stable in an internal consistency test, and of sufficient sensitivity to robustly detect age-related increases in intracranial pulse wave velocity.

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  • 3. Cesaro, Simone
    et al.
    Marsh, Judith
    Tridello, Gloria
    Rovò, Alicia
    Maury, Sebastien
    Montante, Barbara
    Masszi, Tamás
    Van Lint, Maria Teresa
    Afanasyev, Boris
    Iriondo Atienza, Arturo
    Bierings, Marc
    Carbone, Cecilia
    Doubek, Michael
    Lanino, Edoardo
    Sarhan, Mahmoud
    Risitano, Antonio
    Steinerova, Katerina
    Wahlin, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Pegoraro, Anna
    Passweg, Jakob
    Retrospective survey on the prevalence and outcome of prior autoimmune diseases in patients with aplastic anemia reported to the registry of the European group for blood and marrow transplantation.2010Ingår i: Acta Haematologica, ISSN 0001-5792, E-ISSN 1421-9662, Vol. 124, nr 1, s. 19-22Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Aplastic anemia (AA) is rarely described after a diagnosis of autoimmune disease (aID). AIMS: To assess the prevalence of prior aID in patients with AA recorded in the registry of the European Group for Blood and Marrow Transplantation (EBMT) and to evaluate treatment and outcome. METHODS: 1,251 AA patients from 18 EBMT centers were assessed. RESULTS: Fifty patients (4%) were eligible: 22 males and 28 females with a median age of 46 years at the diagnosis of aID and of 51 years at the diagnosis of AA. Information on the treatment of AA was available in 49 patients: 38 received only immunosuppressive therapy (IST), 8 patients underwent hematopoietic stem cell transplantation (HSCT) - 6 as first-line therapy and 2 after failure of IST - whilst 3 patients had a spontaneous recovery. After a median follow-up of 3.19 years, 32 patients were alive, including 7 of the 8 patients who underwent HSCT. Only 6 of 32 patients who were alive at the last follow-up were receiving IST for AA. CONCLUSIONS: Most cases of AA following aID benefitted from IST or HSCT if a matched donor was available. Further prospective investigation is needed to assess the effects of IST on the outcome of underlying aID.

  • 4. Derolf, Asa
    et al.
    Juliusson, Gunnar
    Benson, Lina
    Floisand, Yngvar
    Lazarevic, Vladimir
    Antunovic, Petar
    Mollgard, Lars
    Lehmann, Soren
    Uggla, Bertil
    Wahlin, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Hoglund, Martin
    Deneberg, Stefan
    Decreasing early mortality in acute myeloid leukaemia in Sweden 1997-2014: improving performance status is a major contributing factor2020Ingår i: British Journal of Haematology, ISSN 0007-1048, E-ISSN 1365-2141, Vol. 188, nr 1, s. 187-191Artikel i tidskrift (Refereegranskat)
  • 5. Hallböök, H
    et al.
    Hägglund, H
    Stockelberg, D
    Nilsson, P-G
    Karlsson, K
    Björkholm, M
    Linderholm, M
    Wahlin, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Linder, O
    Smedmyr, B
    Autologous and allogeneic stem cell transplantation in adult ALL: the Swedish Adult ALL Group experience2005Ingår i: Bone Marrow Transplantation, ISSN 0268-3369, E-ISSN 1476-5365, Vol. 35, nr 12, s. 1141-1148Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Adult patients with acute lymphoblastic leukaemia (ALL) have been treated according to national protocols in Sweden since 1986. Stem cell transplantation (SCT) has been recommended in first remission for patients with risk factors for relapse, and for standard risk patients only after relapse. In this retrospective study, the results of autologous and allogeneic SCT in these populations were evaluated. In total, 187 patients with a median age of 34 years (17-66 years) underwent SCT. The 5-year disease-free survival (DFS), for all patients, was 26% (Confidence intervals (CI) 20-32%). The 5-year DFS was higher for patients transplanted in first remission 32% (CI 24-40%) compared to 14% (CI 5-23%; P<0.0001) in patients transplanted beyond first remission. No significant differences in DFS (P=0.06) were determined between autologous, related donor and unrelated donor SCT in the whole cohort. A lower relapse rate was counterbalanced by higher treatment-related mortality in patients undergoing allogeneic SCT. In Philadelphia-positive ALL, allogeneic SCT was superior to autologous SCT, with a 5-year DFS of 30% (CI 12-47%) vs 0% (P=0.04). Limited chronic graft-versus-host-disease (GVHD) was associated with an improved DFS of 53% (CI 38-69%) compared to no chronic GVHD of 22% (CI 10-36%; P=0.0008), indicating a clinically important graft-versus-leukaemia effect.

  • 6.
    Holmlund, Petter
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Stoverud, Karen-Helene
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Wahlin, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Wiklund, Urban
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Malm, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper.
    Jóhannesson, Gauti
    Umeå universitet, Medicinska fakulteten, Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM). Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik.
    Eklund, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Author Response: Posture-Dependent Collapse of the Optic Nerve Subarachnoid Space: A Combined MRI and Modeling Study2021Ingår i: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 62, nr 15, artikel-id 15Artikel i tidskrift (Övrigt vetenskapligt)
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  • 7. Hulegårdh, Erik
    et al.
    Nilsson, Christer
    Lazarevic, Vladimir
    Garelius, Hege
    Antunovic, Petar
    Rangert Derolf, Åsa
    Möllgård, Lars
    Uggla, Bertil
    Wennström, Lovisa
    Wahlin, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Swedish Acute Myeloid Leukemia Group.
    Höglund, Martin
    Juliusson, Gunnar
    Stockelberg, Dick
    Lehmann, Sören
    Characterization and prognostic features of secondary acute myeloid leukemia in a population-based setting: A report from the Swedish Acute Leukemia Registry2015Ingår i: American Journal of Hematology, ISSN 0361-8609, E-ISSN 1096-8652, Vol. 90, nr 3, s. 208-214Artikel i tidskrift (Refereegranskat)
    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.

  • 8.
    Hultdin, Magnus
    et al.
    Umeå universitet, Medicinsk fakultet, Medicinsk biovetenskap, Patologi.
    Sundström, Gunnel
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Medicin.
    Wahlin, Anders
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Medicin.
    Lundström, Berith
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Medicin.
    Samuelsson, Jan
    Birgegård, Gunnar
    Engström Laurent, Anna
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Medicin.
    Progression of bone marrow fibrosis in patients with essential thrombocythemia and polycythemia vera during anagrelide treatment.2007Ingår i: Med Oncol, ISSN 1357-0560, Vol. 24, nr 1, s. 63-70Artikel i tidskrift (Refereegranskat)
  • 9. Iolascon, Achille
    et al.
    Heimpel, Hermann
    Wahlin, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Tamary, Hannah
    Congenital dyserythropoietic anemias: molecular insights and diagnostic approach2013Ingår i: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 122, nr 13, s. 2162-2166Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The congenital dyserythropoietic anemias (CDAs) are hereditary disorders characterized by distinct morphologic abnormalities of marrow erythroblasts. The unveiling of the genes mutated in the major CDA subgroups (I-CDAN1 and II-SEC23B) has now been completed with the recent identification of the CDA III gene (KIF23). KIF23 encodes mitotic kinesin-like protein 1, which plays a critical role in cytokinesis, whereas the cellular role of the proteins encoded by CDAN1 and SEC23B is still unknown. CDA variants with mutations in erythroid transcription factor genes (KLF1 and GATA-1) have been recently identified. Molecular diagnosis of CDA is now possible in most patients.

  • 10. Johansson, J-E
    et al.
    Remberger, M
    Lazarevic, Vlj
    Hallböök, H
    Wahlin, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Kimby, E
    Juliusson, G
    Omar, H
    Hägglund, H
    Allogeneic haematopoietic stem-cell transplantation with reduced intensity conditioning for advanced stage Hodgkin's lymphoma in Sweden: high incidence of post transplant lymphoproliferative disorder.2011Ingår i: Bone Marrow Transplantation, ISSN 0268-3369, E-ISSN 1476-5365, Vol. 46, nr 6, s. 870-875Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Allogeneic transplantation after reduced intensity conditioning (allo-RIC) is a treatment option for patients with Hodgkin's lymphoma (HL) relapsing after autologous transplantation. In all, 23 adult patients with HL underwent allo-RIC in Sweden between 2000 and 2007. The median number of previous treatment lines was five and 20 patients (87%) were previously autografted. TRM at 100 days and at 1 year was 13 and 22% respectively. Acute GVHD grades II-IV developed in 7 out of 23 patients (30%) and chronic GVHD in 10 out of 20 patients at risk (50%). The OS and EFS at three years was 59 and 27%, respectively. Four patients (17%) developed post transplant lymphoproliferative disease (PTLD) after a median time of 55 days (range 38-95); two of these patients later died. The study confirmed that allo-RIC is feasible, but associated with a substantial relapse rate: only 20% of the patients were still alive 7 years after the transplant. A finding of high incidence of PTLD needs to be confirmed in a larger trial that includes patients with non-HL and CLL.

  • 11. Jonsdottir, Gudbjörg
    et al.
    Lund, Sigrún H.
    Björkholm, Magnus
    Turesson, Ingemar
    Wahlin, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    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 study2016Ingår i: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 101, nr 4, s. e145-e148Artikel i tidskrift (Refereegranskat)
  • 12. Juliusson, G
    et al.
    Billström, R
    Gruber, A
    Hellström-Lindberg, E
    Höglunds, M
    Karlsson, K
    Stockelberg, D
    Wahlin, Anders
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin.
    Attitude towards remission induction for elderly patients with acute myeloid leukemia influences survival.2006Ingår i: Leukemia, Vol. 20, nr 1, s. 42-7Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Combination chemotherapy may induce remission from acute myeloid leukemia (AML), but validated criteria for treatment of elderly are lacking. The remission intention (RI) rate for elderly patients, as reported to the Swedish Leukemia Registry, was known to be different when comparing the six health care regions, but the consequences of different management are unknown. The Leukemia Registry, containing 1672 AML patients diagnosed between 1997 and 2001, with 98% coverage and a median follow-up of 4 years, was completed with data from the compulsory cancer and population registries. Among 506 treated and untreated patients aged 70-79 years with AML (non-APL), there was a direct correlation between the RI rate in each health region (range 36-76%) and the two-year overall survival, with no censored observations (6-21%) (chi-squared for trend=11.3, P<0.001; r2=0.86, P<0.02, nonparametric). A 1-month landmark analysis showed significantly better survival in regions with higher RI rates (P=0.003). Differences could not be explained by demographics, and was found in both de novo and secondary leukemias. The 5-year survival of the overall population aged 70-79 years was similar between the regions. Survival of 70-79-year-old AML patients is better in regions where more elderly patients are judged eligible for remission induction.

  • 13. Juliusson, Gunnar
    et al.
    Antunovic, Petar
    Derolf, Åsa
    Lehmann, Sören
    Möllgård, Lars
    Stockelberg, Dick
    Tidefelt, Ulf
    Wahlin, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Höglund, Martin
    Age and acute myeloid leukemia: Real world data on decision to treat and outcomes from the Swedish Acute Leukemia Registry.2009Ingår i: Blood, ISSN 1528-0020, Vol. 113, nr 18, s. 4179-4187Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Acute myeloid leukemia (AML) is most common in the elderly, and most elderly are thought to be unfit for intensive treatment because of the risk of fatal toxicity. The Swedish Acute Leukemia Registry covers 98% of all patients with AML (nonacute promyelocytic leukemia) diagnosed in 1997 to 2005 (n = 2767), with a median follow-up of 5 years, and reports eligibility for intensive therapy, performance status (PS), complete remission rates, and survival. Outcomes were strongly age and PS dependent. Early death rates were always lower with intensive therapy than with palliation only. Long-term survivors were found among elderly given intensive treatment despite poor initial PS. Total survival of elderly AML patients was better in the geographic regions where most of them were given standard intensive therapy. This analysis provides unique real world data from a large, complete, and unselected AML population, both treated and untreated, and gives background to treatment decisions for the elderly. Standard intensive treatment improves early death rates and long-term survival compared with palliation. Most AML patients up to 80 years of age should be considered fit for intensive therapy, and new therapies must be compared with standard induction.

  • 14. Juliusson, Gunnar
    et al.
    Karlsson, Karin
    Lazarevic, Vladimir Lj
    Wahlin, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Brune, Mats
    Antunovic, Petar
    Derolf, Asa
    Hägglund, Hans
    Karbach, Holger
    Lehmann, Sören
    Möllgård, Lars
    Stockelberg, Dick
    Hallböök, Helene
    Höglund, Martin
    Hematopoietic stem cell transplantation rates and long-term survival in acute myeloid and lymphoblastic leukemia: Real-World Population-Based Data From the Swedish Acute Leukemia Registry 1997-20062011Ingår i: Cancer, ISSN 0008-543X, E-ISSN 1097-0142, Vol. 117, nr 18, s. 4238-4246Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Allogeneic stem cell transplantation (alloSCT) reduces relapse rates in acute leukemia, but outcome is hampered by toxicity. Population-based data avoid patient selection and may therefore substitute for lack of randomized trials.

    Methods: We evaluated alloSCT rates within the Swedish Acute Leukemia Registry, including 3899 adult patients diagnosed from 1997 through 2006 with a coverage of 98% and a median follow-up of 6.2 years.

    Results:: AlloSCT rates and survival decreased rapidly with age >55 years. The 8-year overall survival (OS) was 65% in patients <30 years and 38% in patients <60 years and was similar for acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). Among 1073 patients <60 years, alloSCT was performed in 42% and 49% of patients with AML and ALL, respectively. Two-thirds of the alloSCTs were performed in first complete remission, and half used unrelated donors, the same in AML and ALL. Regional differences in management and outcome were found: 60% of AML patients <40 years received alloSCT in all parts of Sweden, but two-thirds of AML patients 40-59 years had alloSCT in one region compared with one-third in other regions (P<.001), with improved 8-year OS among all AML patients in this age cohort (51% vs 30%; P = .005).

    Conclusions: More Swedish AML patients received alloSCT, and long-term survival was better than in recently published large international studies, despite our lack of selection bias. There was no correlation between alloSCT rate and survival in ALL. In adult AML patients <60 years of age, a high alloSCT rate was associated with better long-term survival, but there was no such correlation in ALL.

  • 15. King, Carina
    et al.
    Einhorn, Lena
    Brusselaers, Nele
    Carlsson, Marcus
    Einhorn, Stefan
    Elgh, Fredrik
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
    Frisén, Jonas
    Gustafsson, Åke
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
    Hanson, Stefan
    Hanson, Claudia
    Hedner, Thomas
    Isaksson, Olle
    Jansson, Anders
    Lundkvist, Åke
    Lötvall, Jan
    Lundback, Bo
    Olsen, Björn
    Söderberg-Nauclér, Cecilia
    Wahlin, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Steineck, Gunner
    Vahlne, Anders
    COVID-19: a very visible pandemic2020Ingår i: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 396, nr 10248, s. E15-E15Artikel i tidskrift (Refereegranskat)
  • 16. 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 universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Turesson, Ingemar
    Landgren, Ola
    Patterns of survival and causes of death following a diagnosis of monoclonal gammopathy of undetermined significance. A population-based study.2009Ingår i: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 94, nr 12, s. 1714-1720Artikel i tidskrift (Refereegranskat)
    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.

  • 17. Kristinsson, Sigurdur Y
    et al.
    Björkholm, Magnus
    Goldin, Lynn R
    Blimark, Cecilie
    Mellqvist, Ulf-Henrik
    Wahlin, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Turesson, Ingemar
    Landgren, Ola
    Patterns of hematologic malignancies and solid tumors among 37,838 first-degree relatives of 13,896 patients with multiple myeloma in Sweden.2009Ingår i: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 125, nr 9, s. 2147-2150Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    There are emerging data to suggest a role for genetic factors in the pathogenesis of multiple myeloma (MM). Based on small numbers, certain solid tumors have been reported to occur more frequently among blood relatives of patients with MM. Using population-based data, we assessed risks for hematologic malignancies, monoclonal gammopathy of undetermined significance (MGUS), and solid tumors among first-degree relatives of patients with MM. We included 13,896 patients with MM and 54,365 matched controls. Also we identified first-degree relatives of patients with MM (n = 37,838) and controls (n = 151,068). Using a marginal survival model, we estimated relative risks (RRs) and 95% confidence intervals (CIs) for hematologic and solid tumors among family members of patients with MM and controls as measures of familial aggregation. Compared with relatives of controls, relatives of patients with MM had an increased risk of developing MM (RR = 2.1; 95% CI 1.6-2.9), MGUS (2.1; 1.5-3.1), acute lymphoblastic leukemia (ALL) (2.1; 1.0-4.2), any solid tumor (1.1; 1.0-1.1) and bladder cancer (1.3; 1.0-1.5). No significantly increased risk was found for other hematologic or solid malignancies. Our findings support a role for a shared susceptibility (genetic, environmental or both) that predisposes to MM, MGUS, ALL and bladder cancer.

  • 18. Kristinsson, Sigurdur Y
    et al.
    Pfeiffer, Ruth M
    Björkholm, Magnus
    Goldin, Lynn R
    Schulman, Sam
    Blimark, Cecilie
    Mellqvist, Ulf-Henrik
    Wahlin, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Turesson, Ingemar
    Landgren, Ola
    Arterial and venous thrombosis in monoclonal gammopathy of undetermined significance and multiple myeloma: a population-based study2010Ingår i: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 115, nr 24, s. 4991-4998Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Patients with multiple myeloma (MM) have an increased risk of venous thrombosis. Interestingly, excess risk of venous thromboembolism has been observed among patients with monoclonal gammopathy of undetermined significance (MGUS). Using population-based data from Sweden, we assessed the risks of venous and arterial thrombosis in 18,627 MM and 5326 MGUS patients diagnosed from 1958 to 2006, compared with 70,991 and 20,161 matched controls, respectively. At 1, 5, and 10 years after MM diagnosis, there was an increased risk of venous thrombosis: hazard ratios (95% confidence intervals) were 7.5 (6.4-8.9), 4.6 (4.1-5.1), and 4.1 (3.8-4.5), respectively. The corresponding results for arterial thrombosis were 1.9 (1.8-2.1), 1.5 (1.4-1.6), and 1.5 (1.4-1.5). At 1, 5, and 10 years after MGUS diagnosis, hazard ratios were 3.4 (2.5-4.6), 2.1 (1.7-2.5), and 2.1 (1.8-2.4) for venous thrombosis. The corresponding risks for arterial thrombosis were 1.7 (1.5-1.9), 1.3 (1.2-1.4), and 1.3 (1.3-1.4). IgG/IgA (but not IgM) MGUS patients had increased risks for venous and arterial thrombosis. Risks for thrombosis did not vary by M-protein concentration (> 10.0 g/L or < 10.0 g/L) at diagnosis. MGUS patients with (vs without) thrombosis had no excess risk of MM or Waldenström macroglobulinemia. Our findings are of relevance for future studies and for improvement of thrombosis prophylaxis strategies.

  • 19. Kristinsson, Sigurdur Y
    et al.
    Tang, Min
    Pfeiffer, Ruth M
    Björkholm, Magnus
    Blimark, Cecilie
    Mellqvist, Ulf-Henrik
    Wahlin, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Turesson, Ingemar
    Landgren, Ola
    Monoclonal gammopathy of undetermined significance and risk of skeletal fractures: a population-based study2010Ingår i: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 116, nr 15, s. 2651-2655Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Patients with multiple myeloma (MM) have an increased risk of fractures. On the basis of small numbers, patients with monoclonal gammopathy of undetermined significance (MGUS) have been reported to have an increased fracture risk. Using population-based data from Sweden, we assessed the risks of fractures in 5326 MGUS patients diagnosed from 1958 to 2006, compared with 20 161 matched controls. MGUS patients had an increased risk of any fracture at 5 (hazard ratio [HR] = 1.74; 95% confidence interval [CI], 1.58-1.92) and 10 (HR = 1.61; 95% CI, 1.49-1.74) years. The risk was significantly higher for axial (skull, vertebral/pelvis, and sternum/costae) compared with distal (arm and leg) fractures (P < .001). On the basis of 10 years of follow-up, there was an increased risk of vertebral/pelvic (HR = 2.37; 95% CI, 2.02-2.78), sternal/costae (HR = 1.93; 95% CI, 1.5-2.48), arm (HR = 1.23; 95% CI, 1.06-1.43), leg (HR = 1.40; 95% CI, 1.26-1.56), and other/multiple fractures (HR = 4.25; 95% CI, 3.29-5.51). Risks for fractures did not differ by isotype or M protein concentration at diagnosis. MGUS patients with (versus without) fractures had no excess risk of MM or Waldenström macroglobulinemia. Our results suggest that bone alterations are present in early myelomagenesis. Our findings may have implications for the development of better prophylaxis for bone disease in MGUS, and they provide novel clues on pathogenesis of MM bone disease.

  • 20. Kristinsson, Sigurdur Y
    et al.
    Tang, Min
    Pfeiffer, Ruth M
    Björkholm, Magnus
    Goldin, Lynn R
    Blimark, Cecilie
    Mellqvist, Ulf-Henrik
    Wahlin, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Turesson, Ingemar
    Landgren, Ola
    Monoclonal gammopathy of undetermined significance and risk of infections: a population-based study.2012Ingår i: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 97, nr 6, s. 854-858Artikel i tidskrift (Refereegranskat)
    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.

  • 21. Landgren, Ola
    et al.
    Kristinsson, Sigurdur Y
    Goldin, Lynn R
    Caporaso, Neil E
    Blimark, Cecilie
    Mellqvist, Ulf-Henrik
    Wahlin, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Björkholm, Magnus
    Turesson, Ingemar
    Risk of plasma cell and lymphoproliferative disorders among 14621 first-degree relatives of 4458 patients with monoclonal gammopathy of undetermined significance in Sweden.2009Ingår i: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 114, nr 4, s. 791-795Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Familial clustering of the precursor condition, monoclonal gammopathy of undetermined significance (MGUS) has been observed in case reports and in smaller studies. Using population-based data from Sweden, we identified 4458 MGUS patients, 17505 population-based controls, and first-degree relatives of patients (n = 14621) and controls (n = 58387) with the aim to assess risk of MGUS and lymphoproliferative malignancies among first-degree relatives of MGUS patients. Compared with relatives of controls, relatives of MGUS patients had increased risk of MGUS (relative risk [RR] = 2.8; 1.4-5.6), multiple myeloma (MM; RR = 2.9; 1.9-4.3), lymphoplasmacytic lymphoma/Waldenström macroglobulinemia (LPL/WM; RR = 4.0; 1.5-11), and chronic lymphocytic leukemia (CLL; RR = 2.0; 1.2-2.3). Relatives of patients with IgG/IgA MGUS had a 4.0-fold (1.7-9.2), 2.9-fold (1.7-4.9), and 20-fold (2.3-170) elevated risk of developing MGUS, MM, and LPL/WM, respectively. Relatives of IgM MGUS patients had 5.0-fold (1.1-23) increased CLL risk and nonsignificant excess MM and LPL/WM risks. The results were very similar when we assessed risk by type of first-degree relative, age at MGUS (above/below 65 years), or sex. Risk of non-Hodgkin lymphoma or Hodgkin lymphoma was not increased among MGUS relatives. Among first-degree relatives of a nationwide MGUS cohort, we found elevated risks of MGUS, MM, LPL/WM, and CLL, supporting a role for germline susceptibility genes, shared environmental influences, or an interaction between both.

  • 22. Lanza, Francesco
    et al.
    Campioni, Diana C.
    Hellmann, Andrzej
    Milone, Giuseppe
    Wahlin, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Walewski, Jan
    Spedini, Pierangelo
    Fiamenghi, Cristina
    Cuneo, Antonio
    Knopinska, Wanda
    Swierkowska-Czeneszew, Monica
    Petriz, Jordi
    Fruehauf, Stefan
    Farge, Dominique
    Mohty, Mohamad
    Passweg, Jacob
    Ruuto, Tapani
    Madrigal, Alejandro
    Johnsen, Hans E.
    Individual Quality Assessment of Autografting by Probability Estimation for Clinical Endpoints: A Prospective Validation Study from the European Group for Blood and Marrow Transplantation2013Ingår i: Biology of blood and marrow transplantation, ISSN 1083-8791, E-ISSN 1523-6536, Vol. 19, nr 12, s. 1670-1676Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    The aim of supportive autografting is to reduce the side effects from stem cell transplantation and avoid procedure-related health disadvantages for patients at the lowest possible cost and resource expenditure. Economic evaluation of health care is becoming increasingly important. We report clinical and laboratory data collected from 397 consecutive adult patients (173 non-Hodgkin lymphoma, 30 Hodgkin lymphoma, 160 multiple myeloma, 7 autoimmune diseases, and 28 acute leukemia) who underwent their first autologous peripheral blood stem cell transplantation (PBSCT). We considered primary endpoints evaluating health economic efficacy (eg, antibiotic administration, transfusion of blood components, and time in hospital), secondary endpoints evaluating toxicity (in accordance with Common Toxicity Criteria), and tertiary endpoints evaluating safety (le, the risk of regimen-related death or disease progression within the first year after PBSCT). A time-dependent grading of efficacy is proposed with day 21 for multiple myeloma and day 25 for the other disease categories (depending on the length of the conditioning regimen) as the acceptable maximum time in hospital, which together with antibiotics, antifungal, or transfusion therapy delineates four groups: favorable (<= 7 days on antibiotics and no transfusions; <= 21 [25] days in hospital), intermediate (from 7 to 10 days on antibiotics and <3 transfusions, <= 21 to 25 days in hospital or >= 7 days on antibiotics and no transfusions; from 21 to 30 days [25 to 34] in hospital), unfavorable (>7 days on antibiotics, >3 but <6 transfusions; >30/34 days in hospital after transplantation), and very unfavorable (>10 days on antibiotics, >6 transfusions; >30 to 34 days in hospital). The multivariate analysis showed that (1) PBSC harvests of >= 4 x 10(6)/kg CD34 + cells in 1 apheresis procedure were associated with a favorable outcome in all patient categories except acute myelogenous leukemia and acute lymphoblastic leukemia (P = .001), (2) >= 5 x 10(6)/kg CD34 + cells infused predicted better transplantation outcome in all patient categories (P < .0001) except acute myelogenous leukemia and acute lymphoblastic leukemia, (3) 1 or 2 aphereses (P = .001) predicted good outcome, (4) toxicity increased with higher graft volume reinfused (>500 mL) (P = .002), and (5) patients with a central venous catheter during both collection and infusion of PBSC had a more favorable outcome post-PBSCT than peripheral access (P = .007). The type of mobilization regimen did not affect the outcome of auto-PBSCT. The present study identified predictive variables, which may be useful in future individual pretransplantation probability evaluations with the goal to improve supportive care. (C) 2013 American Society for Blood and Marrow Transplantation.

  • 23. Lazarevic, V.
    et al.
    Horstedt, A-S
    Johansson, B.
    Antunovic, P.
    Billstrom, R.
    Derolf, A.
    Hulegardh, E.
    Lehmann, S.
    Mollgard, L.
    Nilsson, C.
    Peterson, S.
    Stockelberg, D.
    Uggla, B.
    Wennstrom, L.
    Wahlin, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Hoglund, M.
    Juliusson, G.
    Incidence and prognostic significance of karyotypic subgroups in older patients with acute myeloid leukemia: the Swedish population-based experience2014Ingår i: Blood Cancer Journal, E-ISSN 2044-5385, Vol. 4, s. e188-Artikel i tidskrift (Refereegranskat)
    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).

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  • 24.
    Lazarevic, Vladimir
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Andersson, Charlotte
    Wahlin, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Golovleva, Irina
    Chromosome aberrations including der(6)t(2;6)(p15;p21.3) and der(22)t(3;22)(p21;p11) in the evolution of essential thrombocythemia to myelofibrosis with myeloid metaplasia.2006Ingår i: Cancer Genetics and Cytogenetics, ISSN 0165-4608, E-ISSN 1873-4456, Vol. 165, nr 1, s. 87-9Artikel i tidskrift (Refereegranskat)
  • 25.
    Lazarevic, Vladimir
    et al.
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Medicin.
    Golovleva, Irina
    Nygren, Ida
    Wahlin, Anders
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Medicin.
    Induction chemotherapy and post-remission imatinib therapy for de Novo BCR-ABL-positive AML.2006Ingår i: Am J Hematol, ISSN 0361-8609, Vol. 81, nr 6, s. 470-1Artikel i tidskrift (Refereegranskat)
  • 26.
    Lazarevic, Vladimir
    et al.
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Medicin.
    Hägg, Erik
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Medicin.
    Wahlin, Anders
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Medicin.
    Hiccups and severe hyponatremia associated with high-dose cyclophosphamide in conditioning regimen for allogeneic stem cell transplantation.2007Ingår i: Am J Hematol, ISSN 0361-8609, Vol. 82, nr 1, s. 88-Artikel i tidskrift (Refereegranskat)
  • 27.
    Lazarevic, Vladimir
    et al.
    Lund, Sweden.
    Hörstedt, Ann-Sofi
    Lund, Sweden.
    Johansson, Bertil
    Lund, Sweden.
    Antunovic, Petar
    Linköping, Sweden.
    Billström, Rolf
    Skövde, Sweden.
    Derolf, Åsa
    Stockholm and Huddinge, Sweden.
    Lehmann, Sören
    Stockholm and Huddinge, Sweden.
    Möllgård, Lars
    Göteborg, Sweden.
    Peterson, Stefan
    Lund, Sweden.
    Stockelberg, Dick
    Göteborg, Sweden.
    Uggla, Bertil
    Örebro, Sweden.
    Vennström, Lovisa
    Göteborg, Sweden.
    Wahlin, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Höglund, Martin
    Uppsala, Sweden.
    Juliusson, Gunnar
    Lund, Sweden.
    Failure matters: unsuccessful cytogenetics and unperformed cytogenetics are associated with a poor prognosis in a population-based series of acute myeloid leukaemia2015Ingår i: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 94, nr 5, s. 419-423Artikel i tidskrift (Refereegranskat)
    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.

  • 28. Lazarevic, Vladimir L J
    et al.
    Hägglund, Hans
    Remberger, Mats
    Wahlin, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Hallböök, Helene
    Juliusson, Gunnar
    Kimby, Eva
    Malm, Claes
    Omar, Hamdy
    Johansson, Jan-Erik
    Long-term survival following allogeneic or syngeneic stem cell transplant for follicular lymphoma in Sweden2011Ingår i: Leukemia and Lymphoma, ISSN 1042-8194, E-ISSN 1029-2403, Vol. 52, nr 1, s. 69-71Artikel i tidskrift (Refereegranskat)
  • 29.
    Lazarevic, Vladimir Lj
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Liljeholm, Maria
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Forsberg, Karin
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Söderberg, Stefan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Wahlin, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Fludarabine, cyclophosphamide and rituximab (FCR) induced pulmonary hypertension in Waldenstrom macroglobulinemia.2008Ingår i: Leukemia & lymphoma, ISSN 1029-2403, Vol. 49, nr 6, s. 1209-1211Artikel i tidskrift (Refereegranskat)
  • 30. Lazarevic, Vladimir Lj
    et al.
    Remberger, Mats
    Hägglund, Hans
    Hallböök, Helene
    Juliusson, Gunnar
    Kimby, Eva
    Malm, Claes
    Wahlin, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Omar, Hamdy
    Johansson, Jan-Erik
    Myeloablative allogeneic stem cell transplantation for lymphoblastic lymphoma in Sweden: a retrospective study.2011Ingår i: American Journal of Hematology, ISSN 0361-8609, E-ISSN 1096-8652, Vol. 86, nr 8, s. 709-710Artikel i tidskrift (Refereegranskat)
  • 31. Lazarevic, Vladimir Lj
    et al.
    Rosso, Aldana
    Juliusson, Gunnar
    Antunovic, Petar
    Derolf, Asa Rangert
    Deneberg, Stefan
    Mollgard, Lars
    Uggla, Bertil
    Wennstrom, Lovisa
    Wahlin, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Hoglund, Martin
    Lehmann, Soren
    Johansson, Bertil
    Incidence and prognostic significance of isolated trisomies in adult acute myeloid leukemia: A population-based study from the Swedish AML registry2017Ingår i: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 98, nr 5, s. 493-500Artikel i tidskrift (Refereegranskat)
    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.

  • 32. Lazarevic, Vladimir
    et al.
    Remberger, Mats
    Hägglund, Hans
    Juliusson, Gunnar
    Omar, Hamdy
    Halböök, Helene
    Kimby, Eva
    Malm, Claes
    Wahlin, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Johansson, Jan-Erik
    Long-term survival after allogeneic stem cell transplantation for relapsed large B cell lymphomas: a retrospective study2012Ingår i: Leukemia and Lymphoma, ISSN 1042-8194, E-ISSN 1029-2403, Vol. 53, nr 3, s. 503-505Artikel i tidskrift (Refereegranskat)
  • 33. Lazarevic, Vladimir
    et al.
    Rosso, Aldana
    Juliusson, Gunnar
    Antunovic, Petar
    Rangert-Derolf, Asa
    Lehmann, Soren
    Mollgard, Lars
    Uggla, Bertil
    Wennstrom, Lovisa
    Wahlin, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Hoglund, Martin
    Johansson, Bertil
    Prognostic significance of high hyperdiploid and triploid/tetraploid adult acute myeloid leukemia2015Ingår i: American Journal of Hematology, ISSN 0361-8609, E-ISSN 1096-8652, Vol. 90, nr 9, s. 800-805Artikel i tidskrift (Refereegranskat)
    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.

  • 34.
    Lazarevic, Vladimir
    et al.
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Medicin.
    Wahlin, Anders
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Medicin.
    Conditioning with fludarabine alone and allogeneic transplantation as a successful rescue therapy for persistent, severe iatrogenic aplasia after relapse of acute myeloid leukemia.2007Ingår i: Bone Marrow Transplant, ISSN 0268-3369, Vol. 39, nr 1, s. 53-4Artikel i tidskrift (Refereegranskat)
  • 35.
    Lazarevic, Vladimir
    et al.
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Medicin.
    Wahlin, Anders
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Medicin.
    Hultdin, Magnus
    Zhan, Fenguang
    Shaughnessy, John
    Chronic lymphocytic leukemia with osteolytic Richter's syndrome mimicking myeloma bone disease shows no over-expression of DKK1.2006Ingår i: Leukemia and Lymphoma, ISSN 1042-8194, E-ISSN 1029-2403, Vol. 47, nr 9, s. 1987-8Artikel i tidskrift (Refereegranskat)
  • 36. Lehmann, Soren
    et al.
    Lazarevic, Vladimir
    Hörstedt, Ann-Sofi
    Hulegårdh, Erik
    Nilsson, Christer
    Antunovic, Petar
    Derolf, Åsa Rangert
    Möllgård, Lars
    Uggla, Bertil
    Vennström, Lovisa
    Wahlin, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Höglund, Martin
    Stockelberg, Dick
    Juliusson, Gunnar
    Poor Outcome in Secondary Acute Myeloid Leukemia (AML): A First Report From the Population-Based Swedish Acute Leukemia Registry2012Ingår i: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 120, nr 21Artikel i tidskrift (Övrigt vetenskapligt)
  • 37. Lehmann, Sören
    et al.
    Ravn, S
    Carlsson, L
    Antunovic, P
    Deneberg, S
    Möllgård, L
    Rangert Derolf, Å
    Stockelberg, D
    Tidefelt, U
    Wahlin, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Wennström, L
    Högberg, M
    Juliusson, G
    Continuing high early death rate in acute promyelocytic leukemia: a population-based report from the Swedish Adult Acute Leukemia Registry2011Ingår i: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 25, nr 7, s. 1128-1134Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Our knowledge about acute promyelocytic leukemia (APL) patients is mainly based on data from clinical trials, whereas population-based information is scarce. We studied APL patients diagnosed between 1997 and 2006 in the population-based Swedish Adult Acute Leukemia Registry. Of a total of 3897 acute leukemia cases, 3205 (82%) had non-APL acute myeloid leukemia (AML) and 105 (2.7%) had APL. The incidence of APL was 0.145 per 100 000 inhabitants per year. The median age at the time of diagnosis was 54 years; 62% were female and 38% male. Among younger APL patients, female sex predominated (89% of patients <40 years). Of the 105 APL patients, 30 (29%) died within 30 days (that is, early death (ED)) (median 4 days) and 28 (26%) within 14 days from diagnosis. In all, 41% of the EDs were due to hemorrhage; 35% of ED patients never received all-trans-retinoic acid treatment. ED rates increased with age but more clearly with poor performance status. ED was also associated with high white blood cells, lactate dehydrogenase, creatinine, C-reactive protein and low platelet count. Of non-ED patients, 97% achieved complete remission of which 16% subsequently relapsed. In total, 62% are still alive at 6.4 years median follow-up. We conclude that ED rates remain very high in an unselected APL population.

  • 38.
    Liljeholm, Maria
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Grönlund, Elisabeth
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Golovleva, Irina
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Medicinsk och klinisk genetik.
    Sandström, Herbert
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Wahlin, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Erythrocyte Flow Cytometric Analysis in Congenital Dyserythropoietic Anemia Type III-Evaluation of Eosin-5´-Maleimide, CD55, and CD592013Ingår i: Journal of Blood Disorders & Transfusion, ISSN 2155-9864, Vol. 121, nr 23, s. 4791-4799Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Introduction: Flow cytometry with eosin-5´-maleimide (EMA), anti-CD55 and anti-CD59 is commonly used when investigating non-autoimmune hemolytic anemias. Reduced fluorescence of EMA, typically detected in hereditary spherocytosis is also seen in congenital dyserythropoietic anemia type II (CDA II). Reduction of CD55 and CD59 characterizes paroxysmal nocturnal hemoglobinuria (PNH). We studied the flow cytometric profile of EMA, CD55 and CD59 on erythrocytes in congenital dyserythropoietic anemia type III (CDA III). 

    Methods: Erythrocytes from 16 CDA III positive individuals, 14 CDA III negative relatives and three normal controls per assay were studied with flow cytometry after EMA staining. Flow cytometry after anti-CD55 and anti- CD59 was performed on erythrocytes from 12 CDA III positive and 7 CDA III negative relatives with one normal control per assay. 

    Results: CDA III - erythrocytes exhibited marginally stronger fluorescence after EMA-staining than normal controls. Correlation between EMA fluorescence and erythrocyte volume was confirmed. CDA III subjects did not differ from normal controls concerning CD55 and CD59. 

    Conclusion: The results of the present study indicate no abnormality of the erythrocyte membrane in CDA III and show that standard flow cytometry cannot be used to discriminate between CDA III and normal controls. 

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  • 39.
    Liljeholm, Maria
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Irvine, Andrew F
    Vikberg, Ann-Louise
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Medicinsk och klinisk genetik.
    Norberg, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Medicinsk och klinisk genetik.
    Month, Stacy
    Sandström, Herbert
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Wahlin, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Mishima, Masanori
    Golovleva, Irina
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Medicinsk och klinisk genetik.
    Congenital dyserythropoietic anemia type III (CDA III) is caused by a mutation in kinesin family member, KIF232013Ingår i: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 121, nr 23, s. 4791-4799Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Haplotype analysis and targeted next-generation resequencing allowed us to identify a mutation in the KIF23 gene and to show its association with an autosomal dominant form of congenital dyserythropoietic anemia type III (CDA III). The region at 15q23 where CDA III was mapped in a large Swedish family was targeted by array-based sequence capture in a female diagnosed with CDA III and her healthy sister. Prioritization of all detected sequence changes revealed 10 variants unique for the CDA III patient. Among those variants, a novel mutation c.2747C>G (p.P916R) was found in KIF23, which encodes mitotic kinesin-like protein 1 (MKLP1). This variant segregates with CDA III in the Swedish and American families but was not found in 356 control individuals. RNA expression of the 2 known splice isoforms of KIF23 as well as a novel one lacking the exons 17 and 18 was detected in a broad range of human tissues. RNA interference-based knock-down and rescue experiments demonstrated that the p.P916R mutation causes cytokinesis failure in HeLa cells, consistent with appearance of large multinucleated erythroblasts in CDA III patients. We conclude that CDA III is caused by a mutation in KIF23/MKLP1, a conserved mitotic kinesin crucial for cytokinesis.

  • 40.
    Liljeholm, Maria
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Vikberg, Ann-Louise
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Medicinsk och klinisk genetik.
    Golovleva, Irina
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Medicinsk och klinisk genetik.
    Sandström, Herbert
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Wahlin, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Congenital Dyserythropoietic Anemia Type III and Primary Hemochromatosis; Coexistence of Mutations in KIF23 and HFE.2016Ingår i: Journal of Hematology and Blood Disorders, Vol. 1, nr 2, artikel-id 203Artikel i tidskrift (Refereegranskat)
    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.

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  • 41.
    Liljeholm, Maria
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Vikberg, Ann-Louise
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Medicinsk och klinisk genetik.
    Golovleva, Irina
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Medicinsk och klinisk genetik.
    Wahlin, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Congenital dyserythropoietic anemia type III and primary hemochromatosis; coexistence of mutations in KIF23 and HFE2015Ingår i: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 100, s. 594-594Artikel i tidskrift (Övrigt vetenskapligt)
  • 42.
    Lindqvist, Ebba K.
    et al.
    Department of Medicine, Division of Hematology, Karolinska University Hospital Solna and Karolinska Institutet, Stockholm, Sweden.
    Goldin, Lynn R.
    Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD, United States.
    Landgren, Ola
    Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD, United States.
    Blimark, Cecilie
    Department of Medicine, Section of Hematology and Coagulation, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Mellqvist, Ulf-Henrik
    Department of Medicine, Section of Hematology and Coagulation, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Turesson, Ingemar
    Department of Hematology, Skane University Hospital, Malmo, Sweden.
    Wahlin, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Björkholm, Magnus
    Department of Medicine, Division of Hematology, Karolinska University Hospital Solna and Karolinska Institutet, Stockholm, Sweden.
    Kristinsson, Sigurdur Y.
    Department of Medicine, Division of Hematology, Karolinska University Hospital Solna and Karolinska Institutet, Stockholm, Sweden.
    Personal and family history of immune-related conditions increase the risk of plasma cell disorders: a population-based study2011Ingår i: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 118, nr 24, s. 6284-6291Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The associations between immune-related conditions and multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS) have previously been investigated with inconsistent results. In a large population-based study, we identified 19 112 patients with MM, 5403 patients with MGUS, 96 617 matched control subjects, and 262 931 first-degree relatives. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) for the association of MM and MGUS with immune-related conditions by use of logistic regression. A personal history of all infections combined was associated with a significantly increased risk of MM (OR = 1.2; 95% CI, 1.1-1.3), and a personal history of all conditions in the categories infections (OR = 1.6; 95% CI, 1.5-1.7), inflammatory conditions (OR = 1.4; 95% CI, 1.2-1.5), and autoimmune diseases (OR = 2.1; 95% CI, 1.9-2.4) was associated with a significantly increased risk of MGUS. Several specific immune-related conditions elevated the risk of MM and/or MGUS. A family history of autoimmune disease was associated with a significantly increased risk of MGUS (OR = 1.1; 95% CI, 1.00-1.2), but not MM. Our findings suggest that immune-related conditions and/or their treatment are of importance in the etiology of MGUS and possibly MM. The association of both personal and family history of autoimmune disease with MGUS indicates the potential for shared susceptibility for these conditions. (Blood. 2011; 118(24): 6284-6291)

  • 43.
    Lorenz, Fryderyk
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Pawlowicz, Ewa
    Klimkowska, Monika
    Beshara, Soheir
    Brustad, Agnes Bulanda
    Skotnicki, Aleksander B.
    Wahlin, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Machaczka, Maciej
    Ferritinemia and serum inflammatory cytokines in Swedish adults with Gaucher disease type 12018Ingår i: Blood Cells, Molecules & Diseases, ISSN 1079-9796, E-ISSN 1096-0961, Vol. 68, s. 35-42Artikel i tidskrift (Refereegranskat)
    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. 

  • 44. Machaczka, Maciej
    et al.
    Johansson, Jan-Erik
    Remberger, Mats
    Hallböök, Helene
    Malm, Claes
    Lazarevic, Vladimir Lj
    Wahlin, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Omar, Hamdy
    Juliusson, Gunnar
    Kimby, Eva
    Hägglund, Hans
    Allogeneic hematopoietic stem cell transplantation with reduced-intensity conditioning for chronic lymphocytic leukemia in Sweden: Does donor T-cell engraftment 3 months after transplantation predict survival?2012Ingår i: Leukemia and Lymphoma, ISSN 1042-8194, E-ISSN 1029-2403, Vol. 53, nr 9, s. 1699-1705Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Thirty-eight adult patients with chronic lymphocytic leukemia (CLL) underwent reduced-intensity conditioning (RIC) allogeneic stem cell transplantation (allo-SCT) in Sweden between 1999 and 2007. The cumulative incidences of acute GVHD grades II-IV and chronic GVHD were 29% and 48%, respectively. Rates of non-relapse mortality, progression-free survival (PFS) and overall survival (OS) were 18%, 47% and 74% at 1 year, and 21%, 25% and 45% at 5 years, respectively. T-cell chimerism after transplantation was measured in 31 out of 34 patients (91%) surviving beyond day +100. Seventeen patients achieved >90% donor T-cell engraftment at 3 months after allo-SCT and, compared with the 12 patients with ≤90% donor T-cell engraftment, they showed favorable PFS at 1 year (82% vs. 33%, P=0.002), and better long-term PFS and OS (P=0.002 and 0.05 respectively). Donor T-cell engraftment of >90% at 3 months after RIC allo-SCT for CLL seems to predict favorable short-term and long-term outcome.

  • 45.
    Malm, Jan
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper.
    Birnefeld, Johan
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper.
    Zarrinkoob, Laleh
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper. Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Anestesiologi och intensivvård.
    Wåhlin, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Eklund, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Centrum för medicinsk teknik och fysik (CMTF).
    Hemodynamic Disturbances in Posterior Circulation Stroke: 4D Flow Magnetic Resonance Imaging Added to Computed Tomography Angiography2021Ingår i: Frontiers in Neuroscience, ISSN 1662-4548, E-ISSN 1662-453X, Vol. 15, artikel-id 656769Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: A clinically feasible, non-invasive method to quantify blood flow, hemodynamics, and collateral flow in the vertebrobasilar arterial tree is missing. The objective of this study was to evaluate the feasibility of quantifying blood flow and blood flow patterns using 4D flow magnetic resonance imaging (MRI) in consecutive patients after an ischemic stroke in the posterior circulation. We also explore if 4D-flow, analyzed in conjunction with computed tomography angiography (CTA), has potential as a diagnostic tool in posterior circulation stroke.

    Methods: Twenty-five patients (mean age 62 years; eight women) with acute ischemic stroke in the posterior circulation were investigated. At admission, all patients were examined with CTA followed by MRI (4D flow MRI and diffusion-weighted sequences) at median 4 days after the presenting event. Based on the classification of Caplan, patients were divided into proximal/middle (n = 16) and distal territory infarcts (n = 9). Absolute and relative blood flow rates were calculated for internal carotid arteries (ICA), vertebral arteries (VA), basilar artery (BA), posterior cerebral arteries (P1 and P2), and the posterior communicating arteries (Pcom). In a control group consisting of healthy elderly, the 90th and 10th percentiles of flow were calculated in order to define normal, increased, or decreased blood flow in each artery. “Major hemodynamic disturbance” was defined as low BA flow and either low P2 flow or high Pcom flow. Various minor hemodynamic disturbances were also defined. Blood flow rates were compared between groups. In addition, a comprehensive analysis of each patient’s blood flow profile was performed by assessing relative blood flow rates in each artery in conjunction with findings from CTA.

    Results: There was no difference in total cerebral blood flow between patients and controls [604 ± 117 ml/min vs. 587 ± 169 ml/min (mean ± SD), p = 0.39] or in total inflow to the posterior circulation (i.e., the sum of total VA and Pcom flows, 159 ± 63 ml/min vs. 164 ± 52 ml/min, p = 0.98). In individual arteries, there were no significant differences between patients and controls in absolute or relative flow. However, patients had larger interindividual relative flow variance in BA, P1, and P2 (p = 0.01, <0.01, and 0.02, respectively). Out of the 16 patients that had proximal/middle territory infarcts, nine had CTA findings in VA and/or BA generating five with major hemodynamic disturbance identified with 4D flow MRI. For those without CTA findings, seven had no or minor 4D flow MRI hemodynamic disturbance. Among nine patients with distal territory infarcts, one had major hemodynamic disturbances, while the remaining had minor disturbances.

    Conclusion: 4D flow MRI contributed to the identification of the patients who had major hemodynamic disturbances from the vascular pathologies revealed on CTA. We thus conclude that 4D flow MRI could add valuable hemodynamic information when used in conjunction with CTA.

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  • 46.
    Mei, Ya-Fang
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Segerman, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Lindman, Kristina
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Hörnsten, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Wahlin, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Wadell, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Human hematopoietic (CD34+) stem cells possess high-affinity receptors for adenovirus type 11p2004Ingår i: Virology, ISSN 0042-6822, E-ISSN 1096-0341, Vol. 328, nr 2, s. 198-207Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Gene transfer into human hematopoietic stem cells using Ad5 is inefficient due to lack of the primary receptor CAR and the secondary receptors alphavbeta3 integrin and alphavbeta5 integrin, and due to the high seroprevalence of Ad5 antibodies in most adults, resulting in diminished gene transduction. In the present study, we screened six species (species A-F) of adenovirus, displaying different tropisms for interaction with CD34+ cells, at the level of virus attachment and expression. Virus particles were biotinylated and their binding capacity was determined by FACS analysis using streptavidin-FITC. Ad11p, Ad35, and Ad3 (species B) showed high binding affinity, while Ad7, Ad11a (species B), and Ad37 (species D) displayed intermediate affinity. Virions of Ad4 (species E), Ad5 (species C), Ad31 (species A), and Ad41 (species F) hardly bound to hematopoietic progenitor cells. Using a double-labeling system, we demonstrated that adenoviruses bind to quiescent CD34+ cells. Ad11p virions showed the highest affinity among the adenoviruses detected. We further confirmed that virus fiber-specific receptors were present on the hematopoietic progenitor cell surface, because both recombinant fiber of Ad11p and specific antiserum against rfiber could block virus attachment. The ability of the adenoviruses to infect hematopoietic cells was studied by immunofluorescence staining. The adenoviruses from species B and Ad37 showed higher infectivity than Ad31, Ad5, Ad4, and Ad41. Among the studied species B adenoviruses, Ad11p manifested a superior infectivity. Thus, we have confirmed that these cells have high-affinity receptors for species B:2 human adenovirus, Ad11p, and this virus may be used as candidate vector to target therapeutic genes to hematopoietic stem cells.

  • 47. Nilsson, Christer
    et al.
    Hulegårdh, Erik
    Garelius, Hege
    Möllgård, Lars
    Brune, Mats
    Wahlin, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Lenhoff, Stig
    Frödin, Ulla
    Remberger, Mats
    Höglund, Martin
    Juliusson, Gunnar
    Stockelberg, Dick
    Lehmann, Sören
    Secondary Acute Myeloid Leukemia and the Role of Allogeneic Stem Cell Transplantation in a Population-Based Setting2019Ingår i: Biology of blood and marrow transplantation, ISSN 1083-8791, E-ISSN 1523-6536, Vol. 25, nr 9, s. 1770-1778Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Secondary AML (s-AML), including AML with an antecedent hematologic disorder (AHD-AML) and therapy-related AML (t-AML), constitutes a large proportion of patients with AML and is considered to confer a dismal prognosis. The role of allogeneic hematopoietic cell transplantation (HCT) in patients with s-AML and the extent to which HCT is performed in these patients has been little studied to date. We used the population-based Swedish AML Registry comprising 3337 intensively treated adult patients over a 17-year period to study the role of HCT within the group of patients with s-AML as well as compared with patients with de novo AML. HCT was performed in 576 patients (22%) with de novo AML, in 74 patients (17%) with AHD-AML, and in 57 patients (20%) with t-AML. At 5 years after diagnosis, there were no survivors among patients with previous myeloproliferative neoplasms who did not undergo HCT, and corresponding survival for patients with antecedent myelodysplastic syndromes and t-AML was and 2% and 4%, respectively. HCT was compared with chemotherapy consolidation in s-AML using 3 models: (1) a 200-day landmark analysis, in which HCT was favorable compared with conventional consolidation (P = .04, log-rank test); (2) a multivariable Cox regression with HCT as a time-dependent variable, in which the hazard ratio for mortality was 0.73 (95% confidence interval, 0.64 to 0.83) for HCT and favored HCT in all subgroups; and (3) a propensity score matching analysis, in which the 5-year overall survival (OS) and relapse-free survival in patients with s-AML in first complete remission (CR1) was 48% and 43%, respectively, for patients undergoing HCT versus 20% and 21%, respectively, for those receiving chemotherapy consolidation (P = .01 and .02, respectively, log-rank test). Our observational data suggest that HCT improves survival and offers the only realistic curative treatment option in patients with s-AML. 

  • 48.
    Nylander, Elisabet
    et al.
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Dermatologi och venereologi.
    Wahlin, Ylva-Britt
    Umeå universitet, Medicinsk fakultet, Odontologi, Oral diagnostisk radiologi.
    Lundskog, B
    Umeå universitet, Medicinsk fakultet, Medicinsk biovetenskap, Patologi.
    Wahlin, Anders
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Medicin.
    Genital graft-versus-host disease in a male following allogeneic stem cell transplantation2007Ingår i: Acta Dermato-Venereologica, ISSN 0001-5555, E-ISSN 1651-2057, Vol. 87, nr 4, s. 367-368Artikel i tidskrift (Refereegranskat)
  • 49. Olivo, Gaia
    et al.
    Nilsson, Jonna
    Garzón, Benjamín
    Lebedev, Alexander
    Wahlin, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Tarassova, Olga
    Ekblom, Maria M.
    Lövdén, Martin
    Higher VO2max is associated with thicker cortex and lower grey matter blood flow in older adults2021Ingår i: Scientific Reports, E-ISSN 2045-2322, Vol. 11, nr 1, artikel-id 16724Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    VO2max (maximal oxygen consumption), a validated measure of aerobic fitness, has been associated with better cerebral artery compliance and measures of brain morphology, such as higher cortical thickness (CT) in frontal, temporal and cingular cortices, and larger grey matter volume (GMV) of the middle temporal gyrus, hippocampus, orbitofrontal cortex and cingulate cortex. Single sessions of physical exercise can promptly enhance cognitive performance and brain activity during executive tasks. However, the immediate effects of exercise on macro-scale properties of the brain’s grey matter remain unclear. We investigated the impact of one session of moderate-intensity physical exercise, compared with rest, on grey matter volume, cortical thickness, working memory performance, and task-related brain activity in older adults. Cross-sectional associations between brain measures and VO2max were also tested. Exercise did not induce statistically significant changes in brain activity, grey matter volume, or cortical thickness. Cardiovascular fitness, measured by VO2max, was associated with lower grey matter blood flow in the left hippocampus and thicker cortex in the left superior temporal gyrus. Cortical thickness was reduced at post-test independent of exercise/rest. Our findings support that (1) fitter individuals may need lower grey matter blood flow to meet metabolic oxygen demand, and (2) have thicker cortex.

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  • 50. Olsson-Strömberg, Ulla
    et al.
    Simonsson, Bengt
    Ahlgren, Tomas
    Björkholm, Magnus
    Carlsson, Karin
    Gahrton, Gösta
    Hast, Robert
    Löfvenberg, Eva
    Linder, Olle
    Ljungman, Per
    Malm, Claes
    Paul, Christer
    Rodjer, Stig
    Turesson, Ingemar
    Uden, Ann-Mari
    Wahlin, Anders
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Medicin.
    Killander, Andreas
    Wadman, Bengt
    Westin, Jan
    Vikrot, Olle
    Zettervall, Olle
    Öberg, Gunnar
    Comparison of busulphan, hydroxyurea and allogeneic bone marrow transplantation (BMT) in chronic myeloid leukaemia: BMT prolongs survival.2004Ingår i: Hematol J, ISSN 1466-4860, Vol. 5, nr 6, s. 462-6Artikel i tidskrift (Refereegranskat)
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