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  • 1.
    Ahnström Waltersson, Marie
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Oncology . Linköping University, Faculty of Health Sciences.
    Nordenskjöld, Bo
    Linköping University, Department of Clinical and Experimental Medicine, Oncology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology UHL.
    Rutqvist, Lars Erik
    Department of Oncology, Huddinge University Hospital, Stockholm, Sweden.
    Skoog, Lambert
    Department of Cytology, Karolinska Hospital, Stockholm, Sweden.
    Stål, Olle
    Linköping University, Department of Clinical and Experimental Medicine, Oncology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Role of cyclin D1 in ErbB2-positive breast cancer and tamoxifen resistance.2005In: Breast Cancer Research and Treatment, ISSN 0167-6806, E-ISSN 1573-7217, Vol. 91, no 2, p. 145-151Article in journal (Refereed)
    Abstract [en]

    Cyclin D1 plays an important role in the regulation of the G1 phase in the cell cycle. In mammary epithelial cells the expression of cyclin D1 is regulated through the oestrogen receptor and via ErbB2 signalling. Here we investigated the prognostic significance of cyclin D1 among 230 breast cancer patients randomised for tamoxifen, CMF chemotherapy and radiotherapy. The importance of combined cyclin D1 and ErbB2 overexpression was also analysed. Immunohistochemical analysis of the cyclin D1 expression resulted in 69 (29.8%) weakly positive, 107 (46.5%) moderately positive and 54 (23.7%) strongly positive cases. The prognostic importance of ErbB2 was significantly greater for patients whose tumours overexpressed cyclin D1 than for other patients (p = 0.026). In the former group, ErbB2 overexpression was strongly associated with increased risk of recurrence (RR = 4.7; 95% CI, 2.1-10.4) and breast cancer death (RR = 5.4; 95% CI, 2.3-12.6). This result is in accordance with experimental studies demonstrating a link between cyclin D1 and ErbB2 in oncogenesis. Among oestrogen receptor positive patients, those with moderate cyclin D1 expression significantly did benefit from tamoxifen treatment (RR = 0.42; 95% CI, 0.21-0.82) whereas those with weak or strong expression did not. Therefore cyclin D1 might be a predictive marker for tamoxifen resistance.

  • 2. Axdorph, Ulla
    et al.
    Stenke, Leif
    Grimfors, Gunnar
    Carneskog, Jan
    Hansen, Jan
    Linder, Olle
    Ljungman, Per
    Löfvenberg, Eva
    Malm, Claes
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Hematology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology UHL.
    Simonsson, Bengt
    Turesson, Ingemar
    Vilén, Lars
    Udén, Anne-Marie
    Björkholm, Magnus
    Intensive chemotherapy in patients with chronic myelogenous leukaemia (CML) in accelerated or blastic phase - A report from the Swedish CML Group2002In: British Journal of Haematology, ISSN 0007-1048, E-ISSN 1365-2141, Vol. 118, no 4, p. 1048-1054Article in journal (Refereed)
    Abstract [en]

    In attempting to restore the chronic phase (CP) of chronic myelogenous leukaemia (CML), the Swedish CML group utilized an intensive chemotherapy protocol for 83 patients (aged 16-79 years) in accelerated (AP, n = 22) or blastic phase (BC, n = 61). Most patients received a combination of mitoxantrone (12 mg/m2/d) and etoposide (100 mg/m2/d) together with cytosine arabinoside (1 g/m2 b.i.d) for 4 d. Overall, 39 patients (47%) achieved a second CP (CP2)/partial remission (PR). Responding patients <65 years were eligible for ablative chemotherapy followed by an allogeneic (SCT) or a double autologous stem cell transplant (ASCT). Seventeen of 34 responders <65 years failed to proceed to transplantation as a result of early disease progression (n = 15) or disease-related complications (n = 2). The remaining 17 patients underwent SCT (n = 9, including four unrelated donor SCT) or ASCT (n = 8). Only one of the eight ASCT patients had a second ASCT, the remaining seven failed because of progression (n = 5) or hypoplasia (n = 2). The median duration of CP2/PR was 6 months (range 1-72 months). Five patients achieved a longer CP2/PR than CP1. The 1 year survival was 70% for SCT/ASCT patients (median survival 21 months), 50% for responding patients overall, but only 7% for non-responders (P < 0.001). Three SCT/ASCT patients are long-term survivors (65+, 66+ and 73+ months). In conclusion, approximately half of the patients achieved a CP2/PR after intensive chemotherapy, with a clear survival advantage for responders vs non-responders. Subsequent SCT/ASCT was feasible for half of the responders (<65 years), and one individual underwent double ASCT. Novel therapeutic options for CML patients in AP/BP are needed.

  • 3.
    Baron, Frederic
    et al.
    ULg, Liege, Belgium .
    Labopin, Myriam
    University of Paris 06.
    Mohty, Mohamad
    CHU Hotel Dieu, Nantes, France .
    Basara, Nadezda
    University of Leipzig.
    Niederwieser, Dietger
    University of Leipzig.
    Milpied, Noel-Jean
    CHU Bordeaux.
    Cornelissen, J J
    Erasmus University.
    Malm, Claes
    Linköping University, Department of Clinical and Experimental Medicine, Oncology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology UHL.
    Sengeloev, Henrik
    Rigshosp, Copenhagen, Denmark .
    Blaise, Didier
    CHU Marseille.
    Janssen, Jeroen J W M
    Vrije University Amsterdam.
    Petersen, Eefke
    University Medical Centre Utrecht.
    Socie, Gerard
    St Louis Hospital, Paris, France .
    Rocha, Vanderson
    St Louis Hospital, Paris, France .
    Graft-Versus-Leukemia (GVL) Effect After Reduced Intensity Conditioning (RIC) Allogeneic Stem Cell Transplantation (allo-SCT) as Treatment for Acute Myeloid Leukemia (AML): a Survey From the Acute Leukemia Working Party of the EBMT in BLOOD, vol 114, issue 22, pp 1284-12852009In: BLOOD, American Society of Hematology , 2009, Vol. 114, no 22, p. 1284-1285Conference paper (Refereed)
    Abstract [en]

    n/a

  • 4. Brenne, Anne-Tove
    et al.
    Hejna Romstad, Lene
    Gimsing, Peter
    Juliusson, Gunnar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology UHL.
    Turesson, Ingemar
    Romundstad, Pål
    Borset, Magne
    Sundan, Anders
    Waage, Anders
    A low serum level of soluble tumor necrosis factor receptor p55 predicts response to thalidomide in advanced multiple myeloma2004In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 89, no 5, p. 552-556Article in journal (Refereed)
    Abstract [en]

    Background and Objectives. Thalidomide modulates the production of tumor necrosis factor (TNF-α). Soluble TNF receptors, TNFR p55 and TNFR p75, modify TNF-α activity. In this study, we explored the relation between soluble TNF receptors and outcome in patients with advanced multiple myeloma treated with thalidomide. Design and Methods. The levels of soluble TNF receptor p55 and p75 were assessed in serum from 34 myeloma patients with relapsed or refractory disease before starting thalidomide treatment. Serial measurements were performed for 16 patients in serum collected during treatment. Results. The pre-treatment serum level of soluble TNFR p55 in thalidomide responders was significantly lower than that in non-responders (median 1.75 ng/mL (range 1.19-2.84) vs. 2.79 ng/mL (1.36-5.51), p=0.004). The levels of p55 declined significantly during treatment. The levels of p75 showed the same pattern as p55, but the differences were not significant. The median survival of myeloma patients with pre-treatment levels of p55 < 2.79 ng/mL was 404 days, the median survival of patients with pre-treatment levels ≥ 2.79 ng/mL was shorter (65 days, log-rank test p=0.02). Interpretation and Conclusions. We conclude that soluble TNFR p55 is an adverse prognostic factor in myeloma patients with relapsed or refractory disease treated with thalidomide. Patients with a low pre-treatment level of this receptor have a better response rate and a longer overall survival.

  • 5.
    Bäckman, Eva
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology.
    Bergh, Ann-Charlotte
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology.
    Lagerdahl, I
    Rydberg, B
    Sundström, C
    Tobin, G
    Rosenquist, R
    Linderholm, Mats
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology UHL.
    Rosén, Anders
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology.
    Thioredoxin, produced by stromal cells retrieved from the lymph node microenvironment, rescues chronic lymphocytic leukemia cells from apoptosis in vitro2007In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 92, no 11, p. 1495-1504Article in journal (Refereed)
    Abstract [en]

    Background and Objectives: The redox-regulatory protein thioredoxin has several functions including transcriptional regulation, and antioxidant, cytokine, and chemokine activities. We have previously shown that extracellular thioredoxin protects B-cell chronic lymphocytic leukemia (CLL) cells from apoptosis in vitro. In this study we were interested to determine whether thioredoxin is produced by cells surrounding the CLL cells in the in vivo microenvironment and whether this cell-derived thioredoxin has any leukemia growth-promoting effect in vitro. Design and Methods: Lymph nodes from CLL patients (n=25) were analyzed for thioredoxin expression by immunohistology. Stromal cells purified from the lymph nodes were analyzed for thioredoxin secretion at the single cell level using an ELIspot assay. The survival effect of the stromal-derived thioredoxin was tested by co-culturing stromal- and CLL cells with and without Fab-fragments of an anti-thioredoxin antibody. Results: The results indicated that the thioredoxin production correlated with the amount of proliferating cells and was mainly localized to the proliferation centers (pseudofollicles) in the CLL lymph nodes. The leukemia cells per se showed minimal thioredoxin levels, in contrast, stromal cells strongly expressed thioredoxin. Purified primary stromal cells, which secreted extracellular thioredoxin, significantly protected the CLL cells from undergoing apoptosis in 72 h co-cultures. Interestingly, this anti-apoptotic effect could be abrogated by addition of Fab-fragments of an anti- thioredoxin antibody. Interpretation and Conclusions: In conclusion, we have shown that stromal cells in the lymph node microenvironment produce thioredoxin and that the thioredoxin production is localized to the proliferation centers of the CLL lymph nodes. In addition, thioredoxin produced by purified stromal cells rescued CLL cells from apoptosis in vitro. ©2007 Ferrata Storti Foundation.

  • 6.
    Carstensen, John
    et al.
    Linköping University, Faculty of Arts and Sciences. Linköping University, Department of Department of Health and Society, Tema Health and Society.
    Billström, R
    Universitetssjukhuset i Lund.
    Gruber, A
    Karolinska universitetssjukhuset.
    Hellström-Lindberg, E
    Karolinska universitetssjukhuset.
    Höglund, M
    Akademiska sjukhuset i Uppsala.
    Karlsson, Karin
    Hematologi Lunds universitet.
    Stockelberg, D
    Sahlgrenska universitetssjukhuset.
    Wahlin, A
    Norrlands universitetssjukhus.
    Åström, M
    Universitetssjukhuset i Örebro.
    Arnesson, C
    Universitetssjukhuset i Lund.
    Brunell-Abrahamsson, U
    Akademiska sjukhuset i Uppsala.
    Fredriksson, E
    Karolinska universitetssjukhuset.
    Holmberg, E
    Sahlgrenska universitetssjukhuset.
    Wiklund, F
    Norrlands universitetssjukhus.
    Juliusson, Gunnar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology UHL.
    Nordenskjöld, Kerstin
    Attitude towards remission induction for elderly patients with acute myeloid leukemia influences survival2006In: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 20, no 1, p. 42-47Article in journal (Refereed)
    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%) (χ2 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. © 2006 Nature Publishing Group All rights reserved.

  • 7. Crawley, C
    et al.
    Lalanacette, M
    Szydlo, R
    Gilleece, M
    Juliusson, Gunnar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Oncology . Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology UHL.
    Michallet, M
    Mackinnon, S
    Einsele, H
    Reiffers, J
    Zander, AR
    Carreras, E
    Carella, A
    Gratwohl, A
    Sotto, JJ
    Cavenagh, JD
    Niederweiser, D
    Ciceri, F
    Apperley, JF
    Reduced intensity conditioned allografts for myeloma: A study from the Chronic Leukaemia Working Party of the EBMT.2002In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 100, no 11, p. 542-Conference paper (Other academic)
  • 8. Crawley, C
    et al.
    Lalancette, M
    Szydlo, R
    Gilleece, M
    Peggs, K
    Mackinnon, S
    Juliusson, Gunnar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Oncology . Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology UHL.
    Ahlberg, Lucia
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Oncology . Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology UHL.
    Nagler, A
    Shimoni, A
    Sureda, A
    Boiron, JM
    Einsele, H
    Chopra, R
    Carella, A
    Cavenagh, J
    Gratwohl, A
    Garban, F
    Zander, A
    Bjorkstrand, B
    Outcomes for reduced-intensity allogeneic transplantation for multiple myeloma: an analysis of prognostic factors from the Chronic Leukaemia Working Party of the EBMT2005In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 105, no 11, p. 4532-4539Article in journal (Refereed)
    Abstract [en]

    We report the outcome of 229 patients who received an allograft for myeloma with reduced-intensity conditioning (RIC) regimens from 33 centers within the European Group for Blood and Marrow Transplantation (EBMT). The median age was 52 years and 64% were male. Conditioning regimens were heterogeneous, but most were fludarabine based and T cell depleted with antithymocyte globulin or alemtuzumab. Transplantation-related mortality (TRIM) at 1 year was 22%. The 3-year overall survival (OS) and progression-free survival (PFS) were 41% and 21 %, respectively. Adverse OS was associated with chemoresistant disease (relative risk [RR], 2.9), more than 1 prior transplantation (RR, 2.0), and male patients with female donors (FIR, 1.45). Adverse PFS was associated with chemoresistance (RR, 2.4) and alemtuzumab (RR, 1.8). TRM was increased with female-to-male donation (RR, 2.5) and transplantation more than 1 year from diagnosis (RR, 2.3). Grades II to IV acute graft-versus-host disease (aGvHD) occurred in 31%. Chronic GvHD was associated with better OS and PFS and were 84% and 46% for limited, 58% and 30% for extensive, and 29% and 12% in its absence suggesting that a graft-versus-myeloma effect is important. While RIC is feasible, heavily pretreated patients and patients with progressive disease do not benefit.

  • 9. Crawley, CR
    et al.
    Lalancette, M
    Szydlo, R
    Bacigalupo, A
    Lange, A
    Juliusson, Gunnar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Oncology . Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology UHL.
    Ringden, O
    Gratwohl, A
    Mayer, J
    Hansz, J
    Zander, AR
    Vitek, A
    Brune, ML
    Urbano-Ispizua, A
    Niederwieser, D
    Mufti, G
    Apperley, JF
    Reduced intensity conditioned allografts for chronic myeloid leukaemia: A study from the chronic leukaemia working party of the EBMT.2002In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 100, no 11, p. 3089-Conference paper (Other academic)
  • 10. De Angelo, DJ
    et al.
    Schiffer, C
    Stone, R
    Amrein, P
    Fernandez, H
    Bradstock, K
    Tallman, M
    Foran, J
    Juliusson, Gunnar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Oncology . Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology UHL.
    Liu, D
    Paul, C
    Russo, D
    Stenke, L
    Leopold, L
    Stevenson, D
    Richie, M
    Berger, M
    Interim analysis of a phase II study of the safety and efficacy of gemtuzumab ozogamicin (Mylotarg (R)) given in combination with cytarabine and daunorubicin to patients < 60 years old with untreated acute myeloid leukemia.2002In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 100, no 11, p. 745-Conference paper (Other academic)
  • 11.
    Delforge, M.
    et al.
    Katholieke University.
    de Samblanx, H.
    ZNA Middelheim.
    Zervas, K.
    Theagene Anticancer Hospital.
    Katodritou, E.
    Theagen Cancer Centre.
    Sargin, D.
    Istanbul University.
    Hulin, C.
    Central Hospital University Nancy Brabois.
    Ahlberg, Lucia
    Linköping University, Department of Clinical and Experimental Medicine, Oncology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology UHL.
    de la Rubia, J.
    Hospital La Fe.
    Abdulkadyrov, K.
    Russian Science Research Institute.
    Ganguly, R.
    Johnson & Johnson Pharmaceutical.
    Diels, J.
    Johnson & Johnson Pharmaceutical.
    Dhawan, R.
    Johnson & Johnson Pharmaceutical.
    SURVIVAL ANALYSIS OF PATIENTS WITH RELAPSED/REFRACTORY MULTIPLE MYELOMA: AN INTERIM REPORT FROM AN INTERNATIONAL ELECTRONIC OBSERVATIONAL STUDY OF BORTEZOMIB2009In: in HAEMATOLOGICA-THE HEMATOLOGY JOURNAL, vol 94, 2009, Vol. 94, p. 0956-Conference paper (Refereed)
    Abstract [en]

    n/a

  • 12.
    Dimopoulos, Meletios A
    et al.
    Greek Myeloma Study Group, Greece.
    De Samblanx, Hadewijch M
    AZ Sint-Dimpna, ZNA Middelheim, Antwerp, Belgium.
    Roussou, Maria G
    School of Medicine, University of Athens, Athens, Greece.
    Zervas, Konstantinos
    Greek Myeloma Study Group, Greece.
    Katodritou, Eirini
    Department of Hematology, Theagenion Cancer Center, Thessaloniki, Greece.
    Sargin, Deniz
    Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey.
    Hulin, Cyrille
    Hematology, Centre Hospitalier of Nancy-Brabois, Vandoeuvre, France.
    Ahlberg, Lucia
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology UHL.
    De La Rubia, Javier
    Hematology, Hospital La Fe, Valencia, Spain.
    Ganguly, Rita
    Johnson & Johnson Pharmaceuticals, Raritan, NJ, USA.
    Diels, Joris K
    Johnson & Johnson Pharmaceuticals, Beerse, Belgium.
    van de Velde, Helgi
    Johnson & Johnson Pharmaceuticals Research & Development, Beerse, Belgium.
    Dhawan, Ravinder
    Johnson & Johnson Pharmaceuticals, Raritan, NJ, USA.
    Spencer, Michael D
    Johnson & Johnson Pharmaceuticals, High Wycombe, United Kingdom.
    Delforge, Michel
    University Hospital Leuven, Leuven, Belgium .
    Efficacy of Bortezomib Plus Dexamethasone Versus Bortezomib Mono therapy In Patients with Relapsed/Refractory Multiple Myeloma An Interim Report from an International Electronic Observational Study2010In: BLOOD vol 116, issue 21 (ISSN 0006-4971), American Society of Hematology , 2010, Vol. 116, no 21, p. 1247-1248Conference paper (Refereed)
  • 13.
    E Johnsen, H
    et al.
    Aarhus University Hospital.
    Geisler, C
    Rigshosp, Copenhagen, Denmark .
    Juvonen, E
    University Hospital, Helsinki.
    Remes, K
    Turku University Hospital.
    Juliusson, Gunnar
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology UHL.
    Hornsten, P
    University Hospital, Umea.
    Kvaloy, S
    Radiumhospitalet, Oslo.
    Kvalheim, G
    Radiumhospitalet, Oslo.
    Jurgensen, G W
    Herlev University Hospital.
    Pedersen, L M
    Herlev University Hospital.
    Bergmann, O J
    Herlev University Hospital.
    Schmitz, A
    Aarhus University Hospital.
    Boegsted, M
    Aarhus University Hospital.
    Priming with r-metHuSCF and filgrastim or chemotherapy and filgrastim in patients with malignant lymphomas: a randomized phase II pilot study of mobilization and engraftment2011In: BONE MARROW TRANSPLANTATION, ISSN 0268-3369, Vol. 46, no 1, p. 44-51Article in journal (Refereed)
    Abstract [en]

    SCF has been shown to synergize with G-CSF to mobilize CD34(+) PBPCs. In this study we report results from this combination after a phase II trial of 32 patients with malignant lymphoma randomized to receive recombinant methionyl human SCF (ancestim, r-metHuSCF) in combination with recombinant methionyl human G-CSF (filgrastim, r-metHuG-CSF) (experimental arm A) or routine chemotherapy plus filgrastim (conventional arm B). The primary objective was to evaluate the side effects and toxicity during priming and mobilization. The secondary objectives were efficacy by the level of blood-circulating PBPCs, the number of harvest days and the time to three-lineage engraftment after autografting. First, during priming 5 patients had 8 serious events, 4 in each arm. A summary of all adverse events revealed 30 (94%) patients suffering from 132 events of all grading. Second, neutropenia and thrombocytopenia was documented in arm B. Third, 9/14 (64%) patients in arm A reached the target of 5 million CD34(+) cells/kg body weight (bw) compared with 13/15 (87%) in arm B. The results represent the first randomized trial of growth factor plus chemotherapy priming and indicate that a formal phase III trial very unlikely may challenge chemotherapy plus r-metHuG-CSF priming in candidates for high-dose therapy.

  • 14.
    Eliasson, Pernilla
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology.
    Andersson, Patiyan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology.
    Willander, Kerstin
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology.
    Linderholm, Mats
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology UHL.
    Söderkvist, Peter
    Linköping University, Department of Biomedicine and Surgery, Division of cell biology. Linköping University, Faculty of Health Sciences.
    Jönsson, Jan-Ingvar
    Linköping University, Department of Biomedicine and Surgery, Division of cell biology. Linköping University, Faculty of Health Sciences.
    Letter: Absence of hot spot mutations of the PIK3CA gene in acute myeloid leukaemia2006In: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 77, no 1, p. 86-87Article in journal (Other academic)
    Abstract [en]

    [No abstract available]

  • 15.
    Gimsing, Peter
    et al.
    Rigshosp, Copenhagen.
    Carlson, Kristina
    Uppsala University.
    Turesson, Ingemar
    Lund University.
    Fayers, Peter
    University Aberdeen.
    Waage, Anders
    St Olavs University Hospital.
    Vangsted, Annette
    Herlev University Hospital.
    Mylin, Anne
    Rigshosp, Copenhagen.
    Gluud, Christian
    Rigshosp, Copenhagen.
    Juliusson, Gunnar
    Linköping University, Department of Clinical and Experimental Medicine, Oncology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology UHL.
    Gregersen, Henrik
    University Hospital Aalborg.
    Hjorth-Hansen, Henrik
    St Olavs University Hospital.
    Nesthus, Ingerid
    Haukeland Hospital.
    Marie S Dahl, Inger
    University Tromso Hospital.
    Westin, Jan
    Sahlgrens University Hospital.
    Lanng Nielsen, Johan
    Arhus University Hospital.
    Meldgaard Knudsen, Lene
    Herlev University Hospital.
    Ahlberg, Lucia
    Linköping University, Department of Clinical and Experimental Medicine, Oncology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology UHL.
    Hjorth, Martin
    Lidkoping Hospital.
    Abildgaard, Niels
    Odense University Hospital.
    Frost Andersen, Niels
    Arhus University Hospital.
    Linder, Olle
    Orebro University Hospital.
    Wisloeff, Finn
    Ullevaal University Hospital.
    Effect of pamidronate 30 mg versus 90 mg on physical function in patients with newly diagnosed multiple myeloma (Nordic Myeloma Study Group): a double-blind, randomised controlled trial2010In: LANCET ONCOLOGY, ISSN 1470-2045, Vol. 11, no 10, p. 973-982Article in journal (Refereed)
    Abstract [en]

    Background Compared with placebo, prophylactic treatment with bisphosphonates reduces risk of skeletal events in patients with multiple myeloma. However, because of toxicity associated with long-term bisphosphonate treatment, establishing the lowest effective dose is important. This study compared the effect of two doses of pamidronate on health-related quality of life and skeletal morbidity in patients with newly diagnosed multiple myeloma. Methods This double-blind, randomised, phase 3 trial was undertaken at 37 clinics in Denmark, Norway, and Sweden. Patients with multiple myeloma who were starting antimyeloma treatment were randomly assigned in a 1:1 ratio to receive one of two doses of pamidronate (30 mg or 90 mg) given by intravenous infusion once a month for at least 3 years. Randomisation was done by use of a central, computerised minimisation system. Primary outcome was physical function after 12 months estimated by the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire (scale 0-100). All patients who returned questionnaires at 12 months and were still on study treatment were included in the analysis of the primary endpoint. This study is registered with ClinicalTrials. gov, number NCT00376883. Findings From January, 2001, until August, 2005, 504 patients were randomly assigned to pamidronate 30 mg or 90 mg (252 in each group). 157 patients in the 90 mg group and 156 in the 30 mg group were included in the primary analysis. Mean physical function at 12 months was 66 points (95% CI 62.9-70.0) in the 90 mg group and 68 points (64.6-71.4) in the 30 mg group (95% CI of difference -6.6 to 3.3; p=0.52). Median time to first skeletal-related event in patients who had such an event was 9.2 months (8.1-10.7) in the 90 mg group and 10-2 months (7.3-14.0) in the 30 mg group (p=0.63). In a retrospective analysis, eight patients in the pamidronate 90 mg group developed osteonecrosis of the jaw compared with two patients in the 30 mg group. Interpretation Monthly infusion of pamidronate 30 mg should be the recommended dose for prevention of bone disease in patients with multiple myeloma.

  • 16. Gorin, Norbert-Claude
    et al.
    Labopin, Myriam
    Boiron, Jean-Michel
    Theorin, Niklas
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Oncology . Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology UHL.
    Littlewood, Tim
    Slavin, Shimon
    Greinix, Hildegard
    Cahn, Jean Yves
    Alessandrino, E. Paolo
    Rambaldi, Alessandro
    Nagler, Arnon
    Polge, Emmanuelle
    Rocha, Vanderson
    Results of genoidentical hemopoietic stem cell transplantation with reduced intensity conditioning for acute myelocytic leukemia: Higher doses of stem cells infused benefit patients receiving transplants in second remission or beyond - The acute leukemia 2006In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 24, no 24, p. 3959-3966Article in journal (Refereed)
    Abstract [en]

    Purpose Nucleated cell dose is an important and modifiable factor in hematopoietic stem cell transplantation (HSCT), however its association with outcomes in the context of reduced intensity conditioning regimen (RIC) HSCT for adults with acute myelocytic leukemia (AML) is not known. Patients and Methods From 1998 to 2003, 253 patients with de novo AML, received transplants with RIC and peripheral blood from a genoidentical donor. Median age was 55 years (range, 18 to 72) and the median follow-up was 17 months (range, 2 to 67). One hundred forty one patients received transplants in first remission (CRI), 47 received transplants in second remission (CR2), and 65 patients received transplants in a more advanced phase. Fludarabin-based RIC was used in, 91%, of patients and low-dose (<4 Gy) total-body radiation in 23% of patients. The median nucleated and CD34 cell dose infused were 9.1 x 10(8)/kg and 5.8 x 10(6)/kg, respectively. Results,. Overall, 2-year leukemia-free survival (LFS) was 41% +/- 4% and it was 46% +/- 5% for patients receiving a higher cell dose (>9.1 x 10(8)/kg) and 37% +/- 5% for the remainders (P = .03). Higher cell doses exclusively benefited patients who received transplantations in CR2 or beyond, with LFS of 47 +/- 8 versus 20 +/- 8, with no detectable effect for patients who received transplants in CR1. In a multivariate analysis of the overall patient population, higher nucleated cell dose cells were associated with higher LFS (P = .04), higher incidence of chronic graft-versus-host disease (P = .01), and there was a trend towards a lower relapse incidence (P = .06). Interestingly, CD34+ cell dose was not associated with any outcomes. Conclusion Nucleated cell dose is an important factor that can be modified to improve results of RIC for patients with AML transplanted later than om CR1.

  • 17.
    Grabowski, Pawel
    et al.
    Umeå University.
    Hultdin, Magnus
    Karlsson, Karin
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology UHL.
    Tobin, Gerard
    Uppsala University.
    Åleskog, Anna
    Uppsala University.
    Thunberg, Ulf
    Uppsala University.
    Laurell, Anna
    Uppsala University.
    Sundström, Christer
    Uppsala University.
    Rosenquist, Richard
    Uppsala University.
    Roos, Göran
    Umeå University.
    Telomere length as a prognostic parameter in chronic lymphocytic leukemia with special reference to VH gene mutation status2005In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 105, no 12, p. 4807-4812Article in journal (Refereed)
    Abstract [en]

    B-cell chronic lymphocytic leukemia (CLL) consists of 2 prognostic entities where cases with mutated immunoglobulin VH genes have better outcome than unmutated cases. VH-mutated CLLs display longer telomeres compared with unmutated cases and telomere length has been indicated to predict outcome, although the prognostic value of telomere length has not been fully established in CLL. We analyzed telomere length, VH gene mutation status, and clinical parameters in a large series of CLL. Telomere length was assessed by quantitative polymerase chain reaction (PCR), giving a very good correlation to telomere length estimated by Southern blotting (P < .001). The prognostic information given by mutation status (n = 282) and telomere length (n = 246) was significant (P < .001, respectively). Telomere length was a prognostic factor for stage A (P = .021) and stage B/C (P = .018) patients, whereas mutation status predicted outcome only in stage A patients (P < .001). Furthermore, mutated CLLs were subdivided by telomere length into 2 groups with different prognoses (P = .003), a subdivision not seen for unmutated cases (P = .232). Interestingly, the VH-mutated group with short telomeres had an overall survival close to that of the unmutated cases. Thus, by combining VH mutation status and telomere length, an improvedsubclassification of CLL was achieved identifying previouslyunrecognized patient groups with different outcomes. (Blood.2005;105:4807-4812)

  • 18.
    Green, Henrik
    et al.
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Skoglund, Karin
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences.
    Rommel, Franz
    Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology UHL.
    Mirghani, Rajaa A
    Karolinska University Hospital.
    Lotfi, Kourosh
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pharmacology.
    CYP3A activity influences imatinib response in patients with chronic myeloid leukemia: a pilot study on in vivo CYP3A activity2010In: EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY, ISSN 0031-6970, Vol. 66, no 4, p. 383-386Article in journal (Refereed)
    Abstract [en]

    Imatinib is currently used for the treatment of chronic myeloid leukemia (CML). The main metabolite CGP74588 has similar potency to that of imatinib and is a product of CYP3A4 and CYP3A5 metabolism. However, the clinical significance of the metabolism on therapeutic response and pharmacokinetics is still unclear. We designed this study to investigate the role of the CYP3A activity in the response to imatinib therapy. Fourteen CML patients were phenotyped for in vivo CYP3A activity using quinine as a probe drug. The plasma concentration ratio of quinine and its CYP3A metabolite was used for assessing CYP3A activity. The patients were divided into complete molecular responders with undetectable levels of BCR-ABL transcripts after 12 months of therapy and into partial molecular responders who had failed to achieve a complete molecular response. Patients that achieved complete molecular response showed significantly (Mann-Whitney U-test, p = 0.013) higher in vivo CYP3A activity (median quinine metabolic ratio = 10.1) than patients achieving partial molecular response (median = 15.9). These results indicate a clinical significance of the CYP3A activity and its metabolic products in CML patients treated with imatinib.

  • 19. Gruber, A
    et al.
    Björkholm, M
    Brinch, L
    Evensen, S
    Gustavsson, B
    Hedenus, M
    Juliusson, Gunnar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Hematology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology UHL.
    Lofvenberg, E
    Nesthus, I
    Simonsson, B
    Sjö, M
    Stenke, L
    Tangen, JM
    Tidefelt, U
    Uden, AM
    Paul, C
    Liliemark, J
    A phase I/II study of the MDR modulator Valspodar (PSC 833) combined with daunorubicin and cytarabine in patients with relapsed and primary refractory acute myeloid leukemia2003In: Leukemia research: a Forum for Studies on Leukemia and Normal Hemopoiesis, ISSN 0145-2126, E-ISSN 1873-5835, Vol. 27, no 4, p. 323-328Article in journal (Refereed)
    Abstract [en]

    The cyclosporine analog Valspodar (PSC 833, Novartis Pharma) is a strong inhibitor of the mdr1 gene product p-glycoprotein (pgp). A phase I/II study was conducted in order to evaluate if addition of Valspodar to treatment with daunorubicin and cytarabine, given to patients with primary refractory or relapsed acute myeloid leukemia, could increase the complete remission rate. Fifty-three patients were treated in cohorts of three to six patients. Twelve patients reached a complete remission in bone marrow, five of whom also normalized their peripheral blood values. Three patients experienced treatment-related deaths from pneumonia, liver failure and cerebral hemorrhage, respectively. It is concluded that Valspodar 10mg/kg per 24h in combination with daunorubicin 45mg/m2 for 3 days and cytarabine 1g/m2 twice daily for 4 days is tolerable in this heavily pre-treated group of patients. Due to the moderate treatment results, the phase II part of the study was ended prematurely. The modulation of only pgp did not give an obvious improvement of the treatment results in this group of patients. ⌐ 2002 Elsevier Science Ltd. All rights reserved.

  • 20.
    Gréen, Henrik
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Pharmacology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pharmacology.
    Lindqvist Appell, Malin
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Pharmacology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pharmacology.
    Zackrisson, Anna Lena
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Pharmacology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pharmacology.
    Juliusson, Gunnar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Hematology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology UHL.
    Peterson, Curt
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Pharmacology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pharmacology.
    P-gp and mdr-1 mRNA in leukemic cells fromAML patients during chemotheraphy.2001In: Proceedings of the American Association for Cancer Research,2001, 2001, p. 345-355Conference paper (Refereed)
  • 21. Hallbook, H
    et al.
    Hagglund, H
    Stockelberg, D
    Nilsson, PG
    Karlsson, K
    Björkholm, M
    Linderholm, Mats
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology UHL.
    Wahlin, A
    Linder, O
    Smedmyr, B
    Autologous and allogeneic stem cell transplantation in adult ALL: The Swedish Adult ALL Group experience2005In: Bone Marrow Transplantation, ISSN 0268-3369, E-ISSN 1476-5365, Vol. 35, no 12, p. 1141-1148Article in journal (Refereed)
    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 counter-balanced 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. © 2005 Nature Publishing Group All rights reserved.

  • 22. Hallböök, Helene
    et al.
    Simonsson, Bengt
    Ahlgren, Thomas
    Björkholm, Magnus
    Carneskog, Jan
    Grimfors, Gunnar
    Hast, Robert
    Karlsson, Karin
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Hematology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology UHL.
    Kimby, Eva
    Lerner, Richard
    Linder, Olle
    Linderholm, Mats
    Löfvenberg, Eva
    Malm, Claes
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Hematology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology UHL.
    Nilsson, Per-Gunnar
    Paul, Christer
    Stenke, Leif
    Stockelberg, Dick
    Tidefelt, Ulf
    Turesson, Ingemar
    Uden-Blome, Ann-Marie
    Vilen, Lars
    Wahlin, Anders
    Winquist, Ingemar
    Smedmyr, Bengt
    High-dose cytarabine in upfront therapy for adult patients with acute lymphoblastic leukaemia2002In: British Journal of Haematology, ISSN 0007-1048, E-ISSN 1365-2141, Vol. 118, p. 748-754Article in journal (Refereed)
  • 23. Hedenus, M
    et al.
    Birgegård, G
    Näsman, P
    Ahlberg, Lucia
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology UHL.
    Karlsson, T
    Lauri, B
    Lundin, J
    Lärfars, G
    Österborg, A
    Addition of intravenous iron to epoetin beta increases hemoglobin response and decreases epoetin dose requirement in anemic patients with lymphoproliferative malignancies: A randomized multicenter study2007In: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 21, no 4, p. 627-632Article in journal (Refereed)
    Abstract [en]

    This randomized study assessed if intravenous iron improves hemoglobin (Hb) response and permits decreased epoetin dose in anemic (Hb 9-11,11 g/dl), transfusion-independent patients with stainable iron in the bone marrow and lymphoproliferative malignancies not receiving chemotherapy. Patients (n=67) were randomized to subcutaneous epoetin beta 30 000 IU once weekly for 16 weeks with or without concomitant intravenous iron supplementation. There was a significantly (P25%) lower in the iron group, as was the total epoetin dose (P=0.051). In conclusion, the Hb increase and response rate were significantly greater with the addition of intravenous iron to epoetin treatment in iron-replete patients and a lower dose of epoetin was required.

  • 24.
    Höglund, M
    et al.
    Uppsala University Hospital.
    Bjoreman, M
    Örebro University Hospital.
    Björkholm, M
    Karolinska Institutet.
    Brune, M
    Sahlgrenska University Hospital.
    Ekblom, M
    Lund University Hospital.
    Hellström, K
    Regional Oncology Centre Uppsala.
    Lehmann, S
    Karolinska Institutet .
    Ljungman, P
    Karolinska Institutet.
    Malm, Claes
    Linköping University, Department of Clinical and Experimental Medicine, Oncology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology UHL.
    Markevarn, B
    Umeå University Hospital.
    Sandin, F
    Regional Oncology Centre Uppsala.
    Stenke, L
    Karolinska Institutet.
    Wadenvik, H
    Sahlgrenska University Hospital.
    Wahlin, A
    Umeå University Hospital.
    Richter, J
    Lund University Hospital.
    Simonsson, B
    REAL WORLD DATA ON CHRONIC MYELOID LEUKEMIA - A REPORT FROM THE SWEDISH POPULATION BASED CML-REGISTRY in HAEMATOLOGICA-THE HEMATOLOGY JOURNAL, vol 95, issue , pp 337-3382010In: HAEMATOLOGICA-THE HEMATOLOGY JOURNAL, Pensiero Scientifico / Ferrata Storti Foundation , 2010, Vol. 95, p. 337-338Conference paper (Refereed)
    Abstract [en]

    n/a

  • 25. Itälä, M
    et al.
    Geisler, CH
    Kimby, E
    Juvonen, E
    Tjonnfjord, G
    Karlsson, Karin
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Hematology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology UHL.
    Remes, K
    Standard-dose anti-CD20 antibody rituximab has efficacy in chronic lymphocytic leukaemia: Results from a nordic multicentre study2002In: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 69, no 3, p. 129-134Article in journal (Refereed)
    Abstract [en]

    Objectives: This prospective multicentre study was conducted to assess the efficacy of the monoclonal anti-CD20 antibody rituximab in patients with chronic lymphocytic leukaemia (CLL). Secondary objectives were defined as the tolerability and feasibility of rituximab in patients with CLL. Methods: Twenty-four heavily pretreated patients with CLL were treated with a standard dose of 375 mg m-2 of rituximab given once weekly for four doses. Results: The overall response rate was 35% and all the responses were partial as defined by the revised NCI criteria. In 17 (85%) of 20 patients with initially measurable peripheral lymph nodes the size of lymph nodes decreased by at least 50%, while an improvement of the bone marrow infiltration was observed only in two (11%) of 18 evaluable patients. The median duration of the overall response was 12.5 wk. Rituximab was relatively well tolerated. Although side-effects were common (75%) they were usually mild or moderate. There was only one grade 3 adverse event and no grade 4 events. Conclusions: Standard-dose rituximab has activity in heavily pretreated patients with CLL, although the response is mainly limited to the lymph nodes and of short duration. Since rituximab has in vitro synergism with chemotherapeutic agents and is well tolerated by CLL patients, it is reasonable to investigate rituximab in combination with other treatments.

  • 26.
    Juliusson, Gunnar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology UHL.
    Common cytogenetic abnormalities2004In: Chronic lymphocytic leukemia. Molecular genetics, biology, diagnosis, and management / [ed] Guy B. Faguet, Totowa, New Jersey: Humana Press Inc. , 2004, p. 163-171Chapter in book (Other academic)
    Abstract [en]

    A comprehensive and critical review of the latest scientific advances in our understanding of the molecular genetics and biology of CLL and their application to the best management of CLL. The authors focus on diagnosis, prognosis, multifaceted treatment options, and complications. Among the diverse treatments considered are chemotherapy, autologous and allogenic transplantations, monoclonal antibody therapy, immunotoxin therapy, gene therapy, and several new therapeutic strategies. Familial and juvenile chronic lymphocytic leukemia are also discussed

  • 27.
    Juliusson, Gunnar
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Oncology . Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology UHL.
    Celsing, F
    Linkoping Univ Hosp, S-58185 Linkoping, Sweden Karolinska Hosp, S-10401 Stockholm, Sweden Univ Hosp MAS, Malmo, Sweden Cty Hosp, Kalmar, Sweden.
    Turesson, I
    Linkoping Univ Hosp, S-58185 Linkoping, Sweden Karolinska Hosp, S-10401 Stockholm, Sweden Univ Hosp MAS, Malmo, Sweden Cty Hosp, Kalmar, Sweden.
    Adriansson, M
    Linkoping Univ Hosp, S-58185 Linkoping, Sweden Karolinska Hosp, S-10401 Stockholm, Sweden Univ Hosp MAS, Malmo, Sweden Cty Hosp, Kalmar, Sweden.
    Malm, C
    Thalidomide frequently induces good partial remission and best response ever in patients with advanced myeloma and prior high dose melphalan and autotransplant.1999In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 94, no 10, p. 546-Conference paper (Other academic)
  • 28.
    Juliusson, Gunnar
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Hematology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology UHL.
    Celsing, Fredrik
    Turesson, Ingemar
    Lenhoff, Stig
    Adriansson, Magnus
    Malm, Claes
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Hematology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology UHL.
    Frequent good partial remissions from thalidomide including best response ever in patients with advanced refractory and relapsed myeloma2000In: British Journal of Haematology, ISSN 0007-1048, E-ISSN 1365-2141, Vol. 109, no 1, p. 89-96Article in journal (Refereed)
    Abstract [en]

    Twenty-three patients with advanced and heavily pretreated myeloma were treated with thalidomide. Starting dose was 200 mg/d, and 20 patients had dose escalations up to 400 (n = 5), 600 (n = 12) or 800 mg/d (n = 3), usually in divided doses. Nineteen patients were refractory to recent chemotherapy, and four had untreated relapse after prior intensive therapy. Ten out of 23 patients (43%) achieved partial response (PR, nine with refractory and one with relapsed disease), six patients had minor response or stabilization of the disease and four had disease progression. Another three patients died early from advanced myeloma at less than 3 weeks of thalidomide therapy. Of the 10 patients with PR, seven had a better response than after any prior therapy, despite vincristine-doxorubicin-dexamethasone (VAD)-based treatment in all but one and high-dose melphalan with autologous stem cell support in four. Time to achieve PR was rapid in patients receiving thalidomide in divided doses (median 31 d). Responses also included reduced bone marrow plasma cell infiltration and improved general status. Normalized polyclonal gammaglobulin levels were seen in four cases. Six out of 10 patients with PR remained in remission with a median time on treatment of 23 weeks (range 15- 50 weeks). Sedation was common but usually tolerable, and some patients continued full- or part-time work. Four patients had skin problems, three patients had pneumonia, one hypothyrosis, one sinus bradycardia and one minor sensory neuropathy. Thalidomide may induce good partial remissions in advanced refractory myeloma with tolerable toxicity, and should be evaluated in other settings for myeloma patients. Divided thalidomide doses seem to reduce time to achieve remission and may improve response rate.

  • 29.
    Juliusson, Gunnar
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Hematology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology UHL.
    Höglund, Martin
    Karlsson, Karin
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Hematology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology UHL.
    Löfgren, Christina
    Möllgård, Lars
    Paul, Christer
    Tidefelt, Ulf
    Björkholm, Magnus
    Increased remissions from one course for intermediate-dose cytosine arabinoside and idarubicin in elderly acute myeloid leukaemia when combined with cladribine. A randomized population-based phase II study2003In: British Journal of Haematology, ISSN 0007-1048, E-ISSN 1365-2141, Vol. 123, no 5, p. 810-818Article in journal (Refereed)
    Abstract [en]

    Cladribine has single-drug activity in acute myeloid leukaemia (AML), and may enhance the formation of the active metabolite (ara-CTP) of cytosine arabinoside (ara-C). To evaluate the feasibility of adding intermittent cladribine to intermediate-dose ara-C (1 g/m2/2 h) b.i.d. for 4 d with idarubicin (CCI), we performed a 2:1 randomized phase II trial in AML patients aged over 60 years. Primary endpoints were time to recovery from cytopenia and need for supportive care following the first course. Sixty-three patients (median 71 years, range 60-84 years) were included, constituting 72% of all eligible patients. Toxicity was limited, with no differences between the treatment arms. The early toxic death rate was 11%. The median time to recovery from neutropenia and thrombocytopenia was 22 and 17 d from the start of course no. 1, respectively, and the requirement for platelet and red cell transfusions was four and eight units respectively. Patients had a median of 8 d with fever over 38░C, and 17 d with intravenous antibiotic treatment. The overall complete remission (CR) rate was 62%, with 51% CR from one course of CCI in comparison with 35% for the two-drug therapy (P = 0.014). The median survival with a 2-year follow-up was 14 months, and the 2-year survival was over 30%, with no differences between the treatment arms. Considering the median age and our population-based approach, the overall results are encouraging.

  • 30.
    Juliusson, Gunnar
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Oncology . Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology UHL.
    Karlsson, K
    Frodin, U
    Backstrom, G
    Malm, Claes
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Oncology . Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology UHL.
    Subcutaneous Campath1H instead of thymoglobulin in nonmyeloablative allogeneic transplantation: Reduced acute toxicity, but delayed lymphocyte recovery leading to more mixed chimerism, more fatal infections and impaired long-term survival2002In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 100, no 11, p. 1665-Conference paper (Other academic)
  • 31.
    Juliusson, Gunnar
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Hematology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology UHL.
    Karlsson, Karin
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Hematology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology UHL.
    Malm, Claes
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Hematology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology UHL.
    More potent graft-versus-myeloma effect than graft-versus-renal cell cancer effect2002In: Leukemia and Lymphoma, ISSN 1042-8194, E-ISSN 1029-2403, Vol. 43, no 11, p. 2233-2234Article in journal (Refereed)
    Abstract [en]

    [No abstract available]

  • 32.
    Juliusson, Gunnar
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Hematology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology UHL.
    Karlsson, Karin
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Hematology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology UHL.
    Malm, Claes
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Hematology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology UHL.
    Frödin, U
    Mollen, AS
    Backström, G
    Söderkvist, Peter
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    Adjusted conditioning for allogeneic transplantation in a single center setting: Mixed chimerism heralds relapse2003In: Leukemia and Lymphoma, ISSN 1042-8194, E-ISSN 1029-2403, Vol. 44, no 4, p. 669-679Article in journal (Refereed)
    Abstract [en]

    The role of mixed chimerism on subsequent relapse was prospectively evaluated in an allotransplant program. Sixty-six patients with median age of 54 and mainly high-risk hematologic disease and/or solid tumors had individually adjusted non-myeloablative conditioning. Thirty-nine donors were siblings and 27 unrelated. Frequent chimerism analyses supported immune manipulation including donor lymphocyte infusions. The need for transfusions, iv fluids, and antibiotics, and weight loss was less than in a control cohort. Most patients had immediate full and consistent donor chimerism, one-third required immune manipulation. Eight of ten evaluable CML patients were BCR/ABL-negative at days 14-58 post-transplant. Mixed chimerism frequently preceded relapse, and the relapse rate was 38% in 26 patients with mixed chimerism vs. 11% among 35 with consistent full donor chimerism (p = 0.015). The current transplant- and disease-related mortality were 11 and 9%, respectively, among 35 non-high-risk patients, and 35 and 10% for 29 high-risk patients with hematologic malignancy. With a median follow-up of 15 months the 2-year overall survival is 73% for non-high-risk, and 46% for high-risk patients. Adjusted conditioning reduces early toxicity and resource requirements without impairing tumor control, probably due to a rapid establishment of the graft-versus-cancer effect. Mixed chimerism heralded relapse, and tumor-related mortality is not greater with adjusted than with conventional conditioning.

  • 33.
    Juliusson, Gunnar
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Oncology . Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology UHL.
    Lofgren, CR
    Univ Hosp, Linkoping, Sweden Huddinge Univ Hosp, S-14186 Huddinge, Sweden Acad Hosp, Uppsala, Sweden Med Ctr Hosp, Orebro, Sweden Karolinska Hosp, S-10401 Stockholm, Sweden.
    Mollgard, L
    Univ Hosp, Linkoping, Sweden Huddinge Univ Hosp, S-14186 Huddinge, Sweden Acad Hosp, Uppsala, Sweden Med Ctr Hosp, Orebro, Sweden Karolinska Hosp, S-10401 Stockholm, Sweden.
    Paul, C
    Univ Hosp, Linkoping, Sweden Huddinge Univ Hosp, S-14186 Huddinge, Sweden Acad Hosp, Uppsala, Sweden Med Ctr Hosp, Orebro, Sweden Karolinska Hosp, S-10401 Stockholm, Sweden.
    Hoglund, M
    Tidefelt, U
    Univ Hosp, Linkoping, Sweden Huddinge Univ Hosp, S-14186 Huddinge, Sweden Acad Hosp, Uppsala, Sweden Med Ctr Hosp, Orebro, Sweden Karolinska Hosp, S-10401 Stockholm, Sweden.
    Bjorkholm, M
    Univ Hosp, Linkoping, Sweden Huddinge Univ Hosp, S-14186 Huddinge, Sweden Acad Hosp, Uppsala, Sweden Med Ctr Hosp, Orebro, Sweden Karolinska Hosp, S-10401 Stockholm, Sweden.
    No additional toxicity from cladribine (CdA) when given with cytosin arabinoside and idarubicin (CCI) as primary treatment of acute myeloid leukemia in elderly patients: Results from a randomized phase II-study from the leukemia group of middle Sweden (LGMS).2001In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 98, no 11, p. 518-Conference paper (Other academic)
  • 34.
    Juliusson, Gunnar
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology UHL.
    Theorin, Niklas
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology UHL.
    Karlsson, Karin
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology UHL.
    Frödin, U
    Malm, Claes
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology UHL.
    Subcutaneous alemtuzumab vs ATG in adjusted conditioning for allogeneic transplantation: Influence of Campath dose on lymphoid recovery, mixed chimerism and survival2006In: Bone Marrow Transplantation, ISSN 0268-3369, E-ISSN 1476-5365, Vol. 37, no 5, p. 503-510Article in journal (Refereed)
    Abstract [en]

    Sixty-nine consecutive patients (median age 54 years) were prospectively enrolled in a single-institution protocol for allogeneic transplantation with adjusted non-myeloablative fludarabine-melfalan-based conditioning including cyclosporin A and MMF, and one of three modes of serotherapy. Thirty-one donors (45%) were unrelated. The first cohort of 29 had ATG (Thymoglobulin 2 mg/kg × 3 days), the subsequent 26 had Campath 30 mg × 3 days subcutaneously, and the final cohort of 14 had 30 mg Campath once. The groups were similar as regards age, diagnosis and risk factors. Campath-patients had no acute toxicity, fewer days with fever and antibiotics, and required fewer transfusions than ATG-treated patients. 3-d-Campath patients showed lower lymphocyte counts from day + 4, and CD4 +, CD8 +, CD19 + and NK cells recovered slower than in ATG-treated patients. More Campath patients developed mixed chimerism that required DLI. 3-d-Campath induced more serious and opportunistic infections than ATG, which resulted in a greater non-relapse mortality and an impaired overall survival despite a low tumor-related mortality. The change of the Campath dosing schedule to one dose abrogated the deleterious effect of 3-d-Campath on immune recovery, severe infections and survival. Subcutaneous Campath is simple and provides strong immune suppression with no early toxicity, but dose limitation to 30 mg once is recommended. © 2006 Nature Publishing Group. All rights reserved.

  • 35.
    Karlsson, Karin
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Hematology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology UHL.
    Strömberg, Mats
    Liliemark, Jan
    Delannoy, André
    Johnson, S A N
    Porwit, Anja
    Kimby, Eva
    Lärfars, Gerd
    Cristiansen, Ilse
    Nilsson, Göran
    Celsing, Fredrik
    Sundström, Gunnel
    Luthman, Mikaela
    Tidefelt, Ulf
    Wallvik, Jonas
    Juliusson, Gunnar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Hematology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology UHL.
    Oral cladribine for B-cell chronic lymphocytic leukaemia: Report of a phase II trial with a 3-d, 3-weekly schedule in untreated and pretreated patients, and a long-term follow-up of 126 previously untreated patients2002In: British Journal of Haematology, ISSN 0007-1048, E-ISSN 1365-2141, Vol. 116, no 3, p. 538-548Article in journal (Refereed)
    Abstract [en]

    A phase II study was undertaken to evaluate the efficacy and toxicity of a new schedule of cladribine administration (10 mg/m2 orally daily for 3 d every 3 weeks) in 107 patients with B-cell chronic lymphocytic leukaemia (CLL). To minimize toxicity, treatment withdrawal criteria were defined. The results of the 63 previously untreated patients were retrospectively compared with 63 from an earlier study using a 5-d monthly schedule. The compiled data were analysed for prognostic factors for survival. No significant difference regarding response were seen in the two cohorts of the 126 previously untreated patients. The complete response (CR), nodular partial response (nPR) and partial response (PR) rates were 15%, 21% and 41%. Quality of response had no impact on survival. The 3- and 5-year overall survival for previously untreated patients was 73% and 58%, respectively, with a median follow-up of 54 months. Pretreatment haemoglobin < 11.0 g/dl and elevated beta-2-microglobulin had a negative influence on survival. Major infections occurred in 21% of patients in the 3-d study compared with 35% in the 5-d study. The overall response (OR) and CR rates in the 40 previously treated patients were 34% and 5% respectively. Median overall survival was 24 months and median progression-free survival for responding patients was 14 months. Cladribine used as a single agent is an effective treatment with an acceptable safety profile for pretreated and untreated B-CLL. The achievement of complete remission was not a prerequisite for long-term survival.

  • 36.
    Kihlberg, Johan
    et al.
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Radiology. Linköping University, Faculty of Health Sciences.
    Fransson, Sven-Göran
    Linköping University, Department of Medical and Health Sciences, Radiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medical Imaging, Department of Radiology in Linköping.
    Engvall, Jan
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Physiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Clinical Physiology.
    Maret, Eva
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Clinical Physiology. Linköping University, Faculty of Health Sciences.
    Warntjes, Marcel
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Clinical Physiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Clinical Physiology.
    Rommel, Franz
    Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology UHL.
    Ackumulering av överskottsjärn kan bestämmas med MR2009In: Ackumulering av överskottsjärn kan bestämmas med MR, 2009Conference paper (Refereed)
    Abstract [sv]

    Järnöverskott kan vara toxiskt i kroppen. Järnöverskott ses fr a efter multipla blodtransfusioner vid vissa blodsjukdomar. Internationellt är den vanligaste orsaken thalassemi. Antalet patienter med denna problematik är i Sverige ännu begränsat. Järnöverskott kan leda till allvarlig, svårbehandlad hjärtsvikt man kan behandlas med chelaterande perorala läkemedel och styrs då i allmänhet utifrån ferritin/s. Vår hypotes var att överensstämmelsen mellan järnöverskott och transferrin är låg, att järnöverskott bättre karaktäriseras med MR som också kan differentiera mellan järnöverskott i  hjärta respektive lever.

  • 37.
    Lalancette, M
    et al.
    Hammersmith Hosp, London, England UCL, London, England Linkoping Univ Hosp, S-58185 Linkoping, Sweden Hop Edouard Herriot, Lyon, France Hadassah Univ Hosp, IL-91120 Jerusalem, Israel Osped San Martino Genova, Genoa, Italy Univ Leipzig, D-7010 Leipzig, Germany Huddinge Univ Hosp, S-14186 Huddinge, Sweden.
    Rezvani, K
    Hammersmith Hosp, London, England UCL, London, England Linkoping Univ Hosp, S-58185 Linkoping, Sweden Hop Edouard Herriot, Lyon, France Hadassah Univ Hosp, IL-91120 Jerusalem, Israel Osped San Martino Genova, Genoa, Italy Univ Leipzig, D-7010 Leipzig, Germany Huddinge Univ Hosp, S-14186 Huddinge, Sweden.
    Szydlo, R
    Hammersmith Hosp, London, England UCL, London, England Linkoping Univ Hosp, S-58185 Linkoping, Sweden Hop Edouard Herriot, Lyon, France Hadassah Univ Hosp, IL-91120 Jerusalem, Israel Osped San Martino Genova, Genoa, Italy Univ Leipzig, D-7010 Leipzig, Germany Huddinge Univ Hosp, S-14186 Huddinge, Sweden.
    Mackinnon, S
    Hammersmith Hosp, London, England UCL, London, England Linkoping Univ Hosp, S-58185 Linkoping, Sweden Hop Edouard Herriot, Lyon, France Hadassah Univ Hosp, IL-91120 Jerusalem, Israel Osped San Martino Genova, Genoa, Italy Univ Leipzig, D-7010 Leipzig, Germany Huddinge Univ Hosp, S-14186 Huddinge, Sweden.
    Juliusson, Gunnar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Oncology . Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology UHL.
    Michallet, M
    Hammersmith Hosp, London, England UCL, London, England Linkoping Univ Hosp, S-58185 Linkoping, Sweden Hop Edouard Herriot, Lyon, France Hadassah Univ Hosp, IL-91120 Jerusalem, Israel Osped San Martino Genova, Genoa, Italy Univ Leipzig, D-7010 Leipzig, Germany Huddinge Univ Hosp, S-14186 Huddinge, Sweden.
    Slavin, S
    Hammersmith Hosp, London, England UCL, London, England Linkoping Univ Hosp, S-58185 Linkoping, Sweden Hop Edouard Herriot, Lyon, France Hadassah Univ Hosp, IL-91120 Jerusalem, Israel Osped San Martino Genova, Genoa, Italy Univ Leipzig, D-7010 Leipzig, Germany Huddinge Univ Hosp, S-14186 Huddinge, Sweden.
    Frassoni, F
    Hammersmith Hosp, London, England UCL, London, England Linkoping Univ Hosp, S-58185 Linkoping, Sweden Hop Edouard Herriot, Lyon, France Hadassah Univ Hosp, IL-91120 Jerusalem, Israel Osped San Martino Genova, Genoa, Italy Univ Leipzig, D-7010 Leipzig, Germany Huddinge Univ Hosp, S-14186 Huddinge, Sweden.
    Niederwieser, D
    Hammersmith Hosp, London, England UCL, London, England Linkoping Univ Hosp, S-58185 Linkoping, Sweden Hop Edouard Herriot, Lyon, France Hadassah Univ Hosp, IL-91120 Jerusalem, Israel Osped San Martino Genova, Genoa, Italy Univ Leipzig, D-7010 Leipzig, Germany Huddinge Univ Hosp, S-14186 Huddinge, Sweden.
    Gahrton, G
    Hammersmith Hosp, London, England UCL, London, England Linkoping Univ Hosp, S-58185 Linkoping, Sweden Hop Edouard Herriot, Lyon, France Hadassah Univ Hosp, IL-91120 Jerusalem, Israel Osped San Martino Genova, Genoa, Italy Univ Leipzig, D-7010 Leipzig, Germany Huddinge Univ Hosp, S-14186 Huddinge, Sweden.
    Apperley, J
    Hammersmith Hosp, London, England UCL, London, England Linkoping Univ Hosp, S-58185 Linkoping, Sweden Hop Edouard Herriot, Lyon, France Hadassah Univ Hosp, IL-91120 Jerusalem, Israel Osped San Martino Genova, Genoa, Italy Univ Leipzig, D-7010 Leipzig, Germany Huddinge Univ Hosp, S-14186 Huddinge, Sweden.
    Excellent outcome of non-myeloablative stem cell transplant (NMSCT) for good risk myeloma: The EBMT experience.2000In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 96, no 11, p. 872-Conference paper (Other academic)
  • 38.
    Lanemo Myhrinder, Anna
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Cell Biology.
    Hellqvist, Eva
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Cell Biology.
    Sidorova, Ekaterina
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Söderberg, Anita
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Cell Biology.
    Baxendale, Helen
    Infectious Disease & Microbiology Unit, Institute of Child Health, University of London Medical School, London, United Kingdom.
    Dahle, Charlotte
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Willander, Kerstin
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Oncology . Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology UHL.
    Tobin, Gerard
    Department of Genetics and Pathology, Uppsala University, Uppsala, Sweden.
    Bäckman, Eva
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Cell Biology.
    Söderberg, Ola
    Department of Genetics and Pathology, Uppsala University, Uppsala, Sweden.
    Rosenquist, Richard
    Department of Genetics and Pathology, Uppsala University, Uppsala, Sweden.
    Hörkko, Sohvi
    Department of Pharmacology and Toxicology and Biocenter Oulu, University of Oulu, and Clinical Research Center, Oulu University Hospital, Oulu, Finland.
    Rosén, Anders
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Cell Biology.
    A new perspective: molecular motifs on oxidized LDL, apoptotic cells, and bacteria are targets for chronic lymphocytic leukemia antibodies2008In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 111, no 7, p. 3838-3848Article in journal (Refereed)
    Abstract [en]

    The restricted immunoglobulin (Ig) repertoire found in B-cell chronic lymphocytic leukemia (CLL) implies a role for antigen(s) in the leukemogenesis. The nature of the antigens has, however, not been characterized, although examples of autoantigens have been demonstrated. We have analyzed a panel of 28 CLL cell lines and primary cultures, producing monoclonal Ig with different Ig heavy-chain variable region gene usage and mutational status, including several complementarity determining region 3 homology subset members. Using mass-spectrometry, immunoassays, or protein macroarrays, we have discovered novel antigens binding to CLL Igs. These antigens included cytoskeletal proteins vimentin, filamin B, and cofilin-1, but also phosphorylcholine-containing antigens (eg, Streptococcus pneumoniae polysaccharides and oxidized low-density lipoprotein [oxLDL]). Additional new antigens identified were cardiolipin and proline-rich acidic protein-1. Remarkably, these antigens represent molecular motifs exposed on apoptotic cells/blebs and bacteria, and several CLL Igs bound to apoptotic Jurkat cells. In conclusion, these intriguing data, showing a limited target structure recognition, indicate that CD5+ CLL B cells are derived from a cell compartment that produces "natural antibodies," which may be instrumental in elimination and scavenging of apoptotic cells and pathogenic bacteria.

  • 39.
    Lenhoff, S.
    et al.
    Lund University Hospital, Lund, Sweden, Department of Haematology, University Hospital, SE-221 85 Lund, Sweden.
    Hjorth, M.
    Department of Internal Medicine, Lidköping Hospital, Lidköping, Sweden.
    Westin, J.
    Lund University Hospital, Lund, Sweden.
    Brinch, L.
    Rikshospitalet, Oslo, Norway.
    Backstrom, B.
    Bäckström, B., Norrland University Hospital, Umeå, Sweden.
    Carlson, K.
    Uppsala University Hospital, Uppsala, Sweden.
    Christiansen, I.
    Odense University Hospital, Odense, Denmark.
    Dahl, I.M.
    Tromsö University Hospital, Tromsö, Norway.
    Gimsing, P.
    Rigshospitalet, Copenhagen, Denmark.
    Hammerstrom, J.
    Hammerström, J., Trondheim University Hospital, Trondheim, Norway.
    Johnsen, H.E.
    Copenhagen University Hospital, Herlev, Denmark.
    Juliusson, Gunnar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Oncology . Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology UHL.
    Linder, O.
    Örebro University Hospital, Örebro, Sweden.
    Mellqvist, U.-H.
    Sahlgrenska University Hospital, Gothenburg, Sweden.
    Nesthus, I.
    Haukeland Hospital, Bergen, Norway.
    Nielsen, J.L.
    Århus University Hospital, Århus, Denmark.
    Tangen, J.M.
    Ullevål Hospital, Oslo, Norway.
    Turesson, I.
    Malmö University Hospital, Malmö, Sweden.
    Impact of age on survival after intensive therapy for multiple myeloma: A population-based study by the Nordic Myeloma Study Group2006In: British Journal of Haematology, ISSN 0007-1048, E-ISSN 1365-2141, Vol. 133, no 4, p. 389-396Article in journal (Refereed)
    Abstract [en]

    The value of intensive therapy, including autologous stem cell transplantation, in newly diagnosed myeloma patients >60 years is not clear. We evaluated the impact of age (<60 years vs. 60-64 years) on survival in a prospective, population-based setting and compared survival with conventionally treated historic controls. The prospective population comprised 452 patients registered between 1998 and 2000. Of these, 414 received intensive therapy. The historic population, derived from our most recent population-based study on conventional therapy, comprised 281 patients. Of these, 243 fulfilled our eligibility criteria for intensive therapy. For patients undergoing intensive therapy it was found that two factors, beta-2-microglobulin and age <60 years vs. 60-64 years, had independent prognostic impact on survival. However, compared with the historic controls a survival advantage was found both for patients <60 (median 66 months vs. 43 months, P < 0.001) and 60-64 years (median 50 months vs. 27 months, P = 0.001). We conclude that in a population-based setting higher age adversely influences outcome after intensive therapy. Our results indicate that intensive therapy prolongs survival also at age 60-64 years but with less superiority than in younger patients. © 2006 Blackwell Publishing Ltd.

  • 40. Lenhoff, Stig
    et al.
    Hjorth, Martin
    Holmberg, Erik
    Turesson, Ingemar
    Westin, Jan
    Lanng Nielsen, Johan
    Wislöff, Finn
    Brinch, Lorentz
    Carlson, Kristina
    Carlsson, Margaretha
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Hematology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology UHL.
    Dahl, Inger-Marie
    Gimsing, Peter
    Hippe, Erik
    Johnsen, Hans
    Lamvik, Jon
    Löfvenberg, Eva
    Nesthus, Ingerid
    Rödjer, Stig
    Impact on survival of high-dose therapy with autologous stem cell support in patients younger than 60 years with newly diagnosed multiple myeloma: a population-based study.2000In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 95Article in journal (Refereed)
  • 41. Lenhoff, Stig
    et al.
    Hjorth, Martin
    Turesson, Ingemar
    Westin, Jan
    Gimsing, Peter
    Wisloff, Finn
    Ahlberg, Lucia
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Oncology . Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology UHL.
    Carlson, Kristina
    Christiansen, Ilse
    Dahl, Inger Marie
    Forsberg, Karin
    Brinch, Lorentz
    Hammerstrom, Jens
    Johnsen, Hans E.
    Knudsen, Lene Me
    Intensive therapy for multiple myeloma in patients younger than 60 years. Long-term results focusing on the effect of the degree of response on survival and relapse pattern after transplantation2006In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 91, no 9, p. 1228-1233Article in journal (Refereed)
    Abstract [en]

    Background and Objectives. From 1994 to 1997 we conducted a population-based, prospective study on intensive therapy in newly diagnosed symptomatic myeloma patients younger than 60 years, comparing their survival to that of a conventionally treated historic population. Long-term results are presented, including the impact of the degree of response on survival and relapse pattern after transplantation. Design and Methods. The prospective population was formed of 397 patients and the historic population of 313 patients. Both populations were calculated to comprise more than 75% of the expected number of new cases. Results. After a median follow-up of 7 years survival was longer in the prospective population than in the historic one (median 60 versus 39 months, p=0.0002). When comparing only patients eligible for intensive therapy the median survival was 63 versus 44 months (p < 0.0001). Attaining a complete response was associated with prolonged event-free survival but not overall survival. The pattern of relapse after transplantation was heterogeneous but could be divided into four major groups, insidious, classical, plasmacytoma form and transformed disease. The median survival after relapse was 29 months. The relapse pattern and time to relapse predicted outcome. Patients relapsing with an insidious or classical form of disease with skeletal events only, or after a long lasting first response were likely to respond well to conventional salvage therapy. In contrast, relapse with multiple symptoms, transformed disease or a short duration of first response implied bad prognosis. Interpretation and conclusions. The relapse pattern after autologous transplantation is heterogeneous and response to salvage therapy is variable. The degree of response and event-free survival after transplantation are not reliable surrogate markers for survival.

  • 42.
    Liliemark, E
    et al.
    Orebro Med Ctr Hosp, Orebro, Sweden Huddinge Hosp, S-14186 Huddinge, Sweden Karolinska Hosp, Stockholm, Sweden Linkoping Univ, S-58183 Linkoping, Sweden.
    Wang, Y
    Orebro Med Ctr Hosp, Orebro, Sweden Huddinge Hosp, S-14186 Huddinge, Sweden Karolinska Hosp, Stockholm, Sweden Linkoping Univ, S-58183 Linkoping, Sweden.
    Tidefelt, U
    Orebro Med Ctr Hosp, Orebro, Sweden Huddinge Hosp, S-14186 Huddinge, Sweden Karolinska Hosp, Stockholm, Sweden Linkoping Univ, S-58183 Linkoping, Sweden.
    Paul, C
    Orebro Med Ctr Hosp, Orebro, Sweden Huddinge Hosp, S-14186 Huddinge, Sweden Karolinska Hosp, Stockholm, Sweden Linkoping Univ, S-58183 Linkoping, Sweden.
    Gruber, A
    Orebro Med Ctr Hosp, Orebro, Sweden Huddinge Hosp, S-14186 Huddinge, Sweden Karolinska Hosp, Stockholm, Sweden Linkoping Univ, S-58183 Linkoping, Sweden.
    Juliusson, Gunnar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Oncology . Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology UHL.
    Stenke, Lilian
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion.
    Frostvik-Stolt, M
    Orebro Med Ctr Hosp, Orebro, Sweden Huddinge Hosp, S-14186 Huddinge, Sweden Karolinska Hosp, Stockholm, Sweden Linkoping Univ, S-58183 Linkoping, Sweden.
    Zhou, R
    Orebro Med Ctr Hosp, Orebro, Sweden Huddinge Hosp, S-14186 Huddinge, Sweden Karolinska Hosp, Stockholm, Sweden Linkoping Univ, S-58183 Linkoping, Sweden.
    Sundman-Engberg, B
    Orebro Med Ctr Hosp, Orebro, Sweden Huddinge Hosp, S-14186 Huddinge, Sweden Karolinska Hosp, Stockholm, Sweden Linkoping Univ, S-58183 Linkoping, Sweden.
    Gustavsson, B
    Pfister, C
    Orebro Med Ctr Hosp, Orebro, Sweden Huddinge Hosp, S-14186 Huddinge, Sweden Karolinska Hosp, Stockholm, Sweden Linkoping Univ, S-58183 Linkoping, Sweden.
    Liliemark, J
    Orebro Med Ctr Hosp, Orebro, Sweden Huddinge Hosp, S-14186 Huddinge, Sweden Karolinska Hosp, Stockholm, Sweden Linkoping Univ, S-58183 Linkoping, Sweden.
    Etoposide accumulation of AML cells is affected by PSC 833 in vivo and in vitro.1999In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 94, no 10, p. 4055-Conference paper (Other academic)
  • 43. Lindemalm, S
    et al.
    Liliemark, J
    Juliusson, Gunnar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology UHL.
    Larsson, R
    Albertioni, F
    Cytotoxicity and pharmacokinetics of cladribine metabolite, 2-chloroadenine in patients with leukemia2004In: Cancer Letters, ISSN 0304-3835, E-ISSN 1872-7980, Vol. 210, no 2, p. 171-177Article in journal (Refereed)
    Abstract [en]

    The nucleoside analog 2-chlorodeoxyadenosine (Cladribine, CdA) is used in the treatment of patients with several hematological malignancies. After administration of CdA, the major catabolite measured in plasma and urine is 2-chloroadenine (CAde). This study was performed to determine the pharmacokinetics after oral and intravenous (iv) infusion of CdA in patients treated for chronic lymphocytic leukemia and to evaluate the toxicity of CAde to leukemia cells in vitro. CdA and CAde were also determined in plasma from 31 patients and in urine from 16 patients with reversed-phase high-performance liquid chromatographic. The toxicity of CdA and CAde was also determined in leukemic cells from 7 patients by fluorometric microculture cyotoxicity assay. Five times more CAde was quantified after oral treatment compared with an iv infusion of CdA. After iv infusion, the half-life was the same for CdA and CAde, but after oral administration the half-life was doubled for CAde. Excreted amount of CAde in urine constituted about 1.1% after iv infusion and 4.7% after oral CdA treatment. In vitro exposure of leukemia cells to CAde showed that it was eight times less toxic as compared to CdA. We conclude that CAde has a lower cytotoxic effect than CdA but may contribute significantly to the cytotoxicity after oral administration.

  • 44.
    Linderholm, B
    et al.
    Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Bergqvist, J
    Karolinska Institute.
    Hellborg, H
    Karolinska Institute.
    Johansson, U
    Karolinska Institute.
    Linderholm, M
    Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology UHL.
    Elmberger, G
    Karolinska Institute.
    Skoog, L
    Karolinska Institute.
    Bergh, J
    Karolinska Institute.
    Shorter survival-times following adjuvant endocrine therapy in oestrogen- and progesterone-receptor positive breast cancer overexpressing HER2 and/or with an increased expression of vascular endothelial growth factor2009In: MEDICAL ONCOLOGY, ISSN 1357-0560, Vol. 26, no 4, p. 480-490Article in journal (Refereed)
    Abstract [en]

    Purpose: To investigate the possible correlation between expression of HER2 and vascular endothelial growth factor (VEGF), and to determine the predictive value of these factors in patients receiving adjuvant endocrine therapy including the group with a breast cancer (BC) positive for both oestrogen receptor (ER) and progesterone receptor (PgR). Material and methods: By enzyme immuno-sorbent assays (ELISA) tumour levels of HER2 and VEGF proteins were determined in 679 consecutive primary BC patients, median age 63 years, median follow-up time 92 months. A total of 404 patients received adjuvant endocrine therapy, mainly tamoxifen, out of them 295 had an ER and PgR positive BC. In 160 patients, HER2 status was also determined by immunohistochemistry (IHC) using the monoclonal antibody CB11. Results: Overexpression of HER2 by IHC was found in 15% of the patients. Overexpression of HER2 by ELISA correlated with HER2 by IHC (P andlt; 0.001) and a higher VEGF expression (P = 0.004). Patients receiving adjuvant endocrine therapy with high VEGF (RFS P = 0.0087, BCCS P = 0.0012) or over-expressing HER2 (RFS P = 0.0116, BCCS P = 0.0036) had significantly shorter survival. Factors retaining statistical significance in multivariate analyses for recurrence-free survival (RFS) were nodal status (P andlt; 0.001), tumour size (P = 0.005) and VEGF (P = 0.032) and for breast cancer corrected survival (BCCS) nodal status (P andlt; 0.001), tumour size (P = 0.001), ER status (P = 0.022), and VEGF (P = 0.016). Both factors were significantly correlated with survival in the group with a BC positive for both ER and PgR; VEGF (RFS P = 0.0177, BCCS P = 0.0321) and HER2 (RFS P = 0.0143, BCCS P = 0.0311). In multivariate analyses, nodal status (P andlt; 0.001) and VEGF (P = 0.021) were independent factors for RFS. Nodal status (P andlt; 0.001) and tumour size (P = 0.016) retained independent factors for BCCS. Combined analysis identified a high-risk group (HER2 positive and high VEGF) with significantly reduced survival. Conclusion: The results from this retrospective analysis suggest that overexpression of HER2 and higher VEGF expression may add information on patients outcome after adjuvant endocrine therapy in ER and PgR positive BC.

  • 45.
    Linderholm, Mats
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Oncology . Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology UHL.
    Höglund, Martin
    Svensk förening för hematologi Uppsala.
    Stockelberg, Dick
    Svensk förening för hematologi Göteborg.
    Specialist associations' mission: equal and good cancer care for all2008In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 105, no 5, p. 306-307Article in journal (Refereed)
    Abstract [en]

      

  • 46.
    Lj Lazarevic, Vladimir
    et al.
    Lund University.
    Hagglund, Hans
    Karolinska University.
    Remberger, Mats
    Karolinska Institute.
    Wahlin, Anders
    Umeå University Hospital.
    Hallbook, Helene
    Uppsala University Hospital.
    Juliusson, Gunnar
    Lund University.
    Kimby, Eva
    Karolinska University.
    Malm, Claes
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology UHL.
    Omar, Hamdy
    Karolinska University.
    Johansson, Jan-Erik
    Sahlgrens University Hospital.
    Long-term survival following allogeneic or syngeneic stem cell transplant for follicular lymphoma in Sweden2011In: LEUKEMIA and LYMPHOMA, ISSN 1042-8194, Vol. 52, no 1, p. 69-71Article in journal (Refereed)
    Abstract [en]

    n/a

  • 47.
    Lotfi, Kourosh
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Health Sciences, Clinical Pharmacology . Linköping University, Department of Medicine and Health Sciences, Clinical Pharmacology .
    Juliusson, Gunnar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Oncology . Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology UHL.
    Albertioni, Freidoun
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Health Sciences, Clinical Pharmacology .
    Pharmacological basis for cladribine resistance2003In: Leukemia and Lymphoma, ISSN 1042-8194, E-ISSN 1029-2403, Vol. 44, no 10, p. 1705-1712Article in journal (Refereed)
    Abstract [en]

    The inherent or acquired resistance of leukemic cells to cytostatic agents is a major clinical challenge. The purpose of this review was to elucidate and analyse the available data concerning mechanisms of resistance of cladribine with emphasis on recent advances in the characterization of activating and inactivating enzymes in the induction of resistance to cladribine. All available in vitro and clinical data on cladribine was undertaken. Cladribine, unlike many other drugs, is toxic to both dividing and indolent lymphoid malignancies. Cladribine is a prodrug and must be phosphorylated intracellularly to cladribine-monophosphate (MP) by the nuclear/cystosol enzyme deoxycytidine kinase (dCK) and the mitochondrial enzyme deoxyguanosine kinase. The cytotoxicity mainly depends on the accumulation of cladribine-triphosphates (TP) after phosphorylation of cladribine-MP by nucleoside monophosphate kinase and nucleoside diphosphate kinase. 5'-Nucleotidase (5'-NT) dephosphorylates cladribine-MP and the accumulation of cladribine-TP depends on the ratio of dCK and 5'-NT in the cells. The mechanisms underlying cladribine resistance are multifactorial, e.g. decreased nucleoside transport, decreased activity or deficiency of dCK, altered intracellular pools of competing nucleotides, altered regulation of ribonucleotide reductase and increased drug inactivation by 5'-NT. Finally, cladribine resistance may be a consequence of a defective induction of apoptosis. In spite of the fact that more than one mechanism can contribute to a cladribine resistance phenotype, a reduction in dCK activity is probably the major determinant of cladribine resistance. Insight into the mechanism of action and resistance to cladribine is crucial for its optimal use as well as for the development of newer analogues.

  • 48.
    Lotfi, Kourosh
    et al.
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Pharmacology.
    Karlsson, Karin
    Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology UHL.
    Fyrberg, Anna
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Juliusson, Gunnar
    Lund University Hospital.
    Jonsson, Viggo
    Oslo University.
    Peterson, Curt
    Linköping University, Department of Medicine and Care, Clinical Pharmacology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Pharmacology.
    Eriksson, Staffan
    Swedish University of Agricultural Sciences, The Biomedical Center, Uppsala.
    Albertioni, Freidoun
    Linköping University, Department of Medicine and Care, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    The pattern of deoxycytidine- and deoxyguanosine kinase activity in relation to messenger RNA expression in blood cells from untreated patients with B-cell chronic lymphocytic leukemia2006In: Biochemical Pharmacology, ISSN 0006-2952, E-ISSN 1356-1839, Vol. 71, no 6, p. 882-890Article in journal (Refereed)
    Abstract [en]

    Deoxycytidine kinase (dCK) and deoxyguanosine kinase (dGK) catalyze the first step in the intracellular cascade of fludarabine (2-fluoroadenine-β- d-arabinofuranoside) and cladribine (2-chlorodeoxyadenosine) phosphorylation, which leads to activation of these prodrugs, commonly used for treatment of chronic lymphocytic leukemia (CLL). Thus, resistance to nucleoside analogues may primarily be due to low levels of deoxynucleoside kinase activity. The purpose of this study was to investigate the activity profiles of dCK and dGK and characterize the possible relationship between the levels of dCK enzymatic activities and mRNA levels in B-CLL cells from untreated patient samples in an attempt to determine the best approach for predicting sensitivity to nucleoside analogues and thereby optimizing treatment of CLL. For this purpose, dCK and dGK analyses were done in blood cells from 59 untreated symptomatic patients with CLL. The dGK activity towards 2-chlorodeoxyadenosine was significantly lower than of dCK (median 73 pmol/mg protein/min (85-121, 95% CI) versus 353 pmol/mg protein/min (331-421)). The median dCK mRNA level was 0.107 (0.096-0.120, 95% CI). There was a lack of correlation between the activities of dCK and dGK, which indicates that these proteins are regulated independently. We also found that the dCK and dGK activity measurement towards their endogenous substrates were comparable to the nucleoside analogues tested. Such variations in enzyme activities and mRNA levels may well explain differences in clinical responses to treatment. There was no correlation between the levels of dCK mRNAs and enzymatic activities using a quantitative real-time PCR procedure. Sequencing of dCK mRNA did not reveal alternate splicing or mutations in the coding region. The relation between activity and mRNA levels was studied by short interfering RNA (siRNA) method, which showed that in the siRNA treated cells the down-regulation of dCK expression, and activity followed each other. However, in control cells the mRNA levels remained stable but the protein activity markedly decreased. These data demonstrate that the dCK activity is not reflected by dCK mRNA expression that indicates a post-translational mechanism(s). © 2005 Elsevier Inc. All rights reserved.

  • 49.
    Lotfi, Kourosh
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Pharmacology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pharmacology.
    Peterson, Curt
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Pharmacology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pharmacology.
    Juliusson, Gunnar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology UHL.
    Letter: Monitoring oral cyclosporine therapy2005In: Bone Marrow Transplantation, ISSN 0268-3369, E-ISSN 1476-5365, Vol. 36, p. 367-367Article in journal (Other academic)
  • 50. Lundin, J
    et al.
    Hagberg, H
    Repp, R
    Cavallin-Stahl, E
    Freden, S
    Juliusson, Gunnar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Oncology . Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology UHL.
    Rosenblad, E
    Tjonnfjord, G
    Wiklund, T
    Osterborg, A
    Phase 2 study of alemtuzumab (anti-CD52 monoclonal antibody) in patients with advanced mycosis fungoides/Sezary syndrome2003In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 101, no 11, p. 4267-4272Article in journal (Refereed)
    Abstract [en]

    This phase 2 study evaluated the safety and efficacy of alemtuzumab in 22 patients with advanced mycosis fungoides/Sezary syndrome (MF/SS). Most patients had stage III or IV disease, reduced performance status, and severe itching. The overall response (OR) rate was 55%, with 32% of patients in complete remission (CR) and M in, partial remission (PR). Sezary cells were cleared from the blood in 6 of 7 (86%) patients, and CR in lymph nodes was observed in 6 of 11 (55%) patients. The effect was better on erythro-derma (OR, 69%) than on plaque or skin tumors (OR, 40%) and in patients who had received 1 to 2 previous regimens (OR, 80%) thin in those who had received 3 or more prior regimens (OR, 33%). Itching, self-assessed on a 0 to 10 visual analog scale, was reduced from a median of 8 before treatment to 2 at end. of therapy. Median time to treatment failure was 12 months (range, 5-32+ months). Cytomegalovirus (CMV), reactivation (causing fever without pneumonitis and responding to ganciclovir) occurred in 4 (18%) patients. Six additional patients had suspect or manifest infection (fever of unknown origin, 3, generalized herpes simplex, 1, fatal aspergillosis, 1). One patient had fatal Mycobacterium pneumonia at 10+ months. All serious infectious adverse events (except CMV) occurred in patients who had received 3 or more prior regimens. Progression of squamous cell skin carcinoma was noted in 1 patient. Alemtuzumab shows promising clinical activity and an acceptable safety profile in patients with advanced MF/SS, particularly in patients with erythroderma and severe itching and those who were not heavily pretreated. (C) 2003 by The American Society of Hematology.

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