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  • 1. 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.

  • 2.
    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.

  • 3. Castor, Anders
    et al.
    Nilsson, Lars
    Åstrand-Grundström, Ingbritt
    Buitenhuis, Miranda
    Ramirez, Carole
    Anderson, Kristina
    Strömbeck, Bodil
    Garwicz, Stanislaw
    Békássy, Albert N
    Schmiegelow, Kjeld
    Lausen, Birgitte
    Hokland, Peter
    Lehmann, Sören
    Juliusson, Gunnar
    Lund University .
    Johansson, Bertil
    Jacobsen, Sten Eirik W
    Distinct patterns of hematopoietic stem cell involvement in acute lymphoblastic leukemia2005In: Nature Medicine, ISSN 1078-8956, E-ISSN 1546-170X, Vol. 11, no 6, p. 630-637Article in journal (Refereed)
    Abstract [en]

    The cellular targets of primary mutations and malignant transformation remain elusive in most cancers. Here, we show that clinically and genetically different subtypes of acute lymphoblastic leukemia (ALL) originate and transform at distinct stages of hematopoietic development. Primary ETV6-RUNX1 (also known as TEL-AML1) fusions and subsequent leukemic transformations were targeted to committed B-cell progenitors. Major breakpoint BCR-ABL1 fusions (encoding P210 BCR-ABL1) originated in hematopoietic stem cells (HSCs), whereas minor BCR-ABL1 fusions (encoding P190 BCR-ABL1) had a B-cell progenitor origin, suggesting that P190 and P210 BCR-ABL1 ALLs represent largely distinct tumor biological and clinical entities. The transformed leukemia-initiating stem cells in both P190 and P210 BCR-ABL1 ALLs had, as in ETV6-RUNX1 ALLs, a committed B progenitor phenotype. In all patients, normal and leukemic repopulating stem cells could successfully be separated prospectively, and notably, the size of the normal HSC compartment in ETV6-RUNX1 and P190 BCR-ABL1 ALLs was found to be unaffected by the expansive leukemic stem cell population.

  • 4. 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)
  • 5. 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.

  • 6. Crawley, C
    et al.
    Szydlo, R
    Lalancette, M
    Bacigalupo, A
    Lange, A
    Brune, M
    Juliusson, Gunnar
    Nagler, A
    Gratwohl, A
    Passweg, J
    Komarnicki, M
    Vitek, A
    Mayer, J
    Zander, A
    Sierra, J
    Rimbaldi, A
    Ringden, O
    Niederwieser, D
    Apperley, JF
    Outcomes of reduced-intensity transplantation for chronic myeloid leukemia: an analysis of prognóstic factors from the Chronic Leukemia Working Party of the EBMT2005In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 106, no 9, p. 2969-2976Article in journal (Refereed)
    Abstract [en]

    This study reports outcomes of allogeneic hematopoietic stem cell transplantation with reduced-intensity conditioning (RIC) in 186 patients with chronic myeloid leukemia (CML) from the European Group for Blood and Marrow Transplantation (EBMT). The median age was 50 years, and 64% were in first chronic phase (CP1), CP2 13%, accelerated phase 17%, and blast crises 6%. The median EBMT transplant score was 3. The day 100 transplantation-related mortality (TRM) was 6.1% (confidence interval [CI], 3.4%-11%) but rose to 23.3% (CI, 14%-27%) at 2 years. Fludarabine, busulfan, and antithymocyte globulin (Fd/Bu/ATG) was associated with the lowest TRM of 11.6% (CI, 4.7%-11%) at 1 year. Acute graft-versus-host disease (GvHD) grade II to IV occurred in 32% and chronic GvHD in 43% (extensive in 24%). ATG was associated with a lower incidence of chronic GvHD (cGvHD). The overall survival (OS) and progression-free survival (PFS) at 3 years were 58% (CI, 50%-66%) and 37% (CI, 30%-45%), respectively. Adverse OS was associated with advanced disease (relative risk [RR], 3.4). PFS was inferior in advanced disease (RR, 2.7) and a trend to improved outcomes with Fd/Bu/ATG (RR, 0.58). RIC allografts are feasible in CML in first or second CP. Since no other RIC regimen demonstrated superiority, Fd/Bu/ATG should be considered as baseline in future prospective trials.

  • 7. 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)
  • 8. 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)
  • 9.
    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.

  • 10.
    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.

  • 11. 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.

  • 12.
    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)
  • 13.
    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

  • 14.
    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)
  • 15.
    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.

  • 16.
    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.

  • 17.
    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)
  • 18.
    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]

  • 19.
    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.

  • 20.
    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)
  • 21.
    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.

  • 22.
    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.

  • 23.
    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)
  • 24.
    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.

  • 25.
    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)
  • 26. 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.

  • 27.
    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.

  • 28.
    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.

  • 29.
    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
    Lund Strategic Centre for Stem Cell Biology and Therapy, Department of Hematology, Lund University Hospital, Lund, Sweden.
    Monitoring oral cyclosporine therapy2005In: Bone Marrow Transplantation, ISSN 0268-3369, E-ISSN 1476-5365, Vol. 36, p. 367-367Article in journal (Other academic)
  • 30. 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.

  • 31.
    Mulligan, Stephen P.
    et al.
    Royal N Shore Hospital, Australia.
    -Karlsson, Karin
    Department of Hematology, Skåne University Hospital, Lund , Sweden.
    Stromberg, Mats
    Karolinska University Hospital, Sweden.
    Jonsson, Viggo
    National Hospital, Denmark.
    Gill, Devinder
    Princess Alexandra Hospital, Australia.
    Hammerstrom, Jens
    St Olavs University Hospital, Norway.
    Hertzberg, Mark
    Westmead Hospital, Australia.
    McLennan, Roger
    Ballarat Base Hospital, Australia.
    Uggla, Bertil
    University Hospital Örebro, Sweden.
    Norman, John
    Royal Adelaide Hospital, Australia.
    Wallvik, Jonas
    Department Med, Sweden.
    Sundstrom, Gunnel
    Norrlands University Hospital, Sweden.
    Johansson, Hemming
    Karolinska Institute, Sweden.
    Brandberg, Yvonne
    Karolinska Institute, Sweden.
    Liliemark, Jan
    Karolinska University Hospital, Sweden; Swedish Council Health Technology Assessment, Sweden.
    Juliusson, Gunnar
    Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Haematology. Department of Hematology, Sk å ne University Hospital, Lund, Sweden.
    Cladribine prolongs progression-free survival and time to second treatment compared to fludarabine and high-dose chlorambucil in chronic lymphocytic2014In: Leukemia and Lymphoma, ISSN 1042-8194, E-ISSN 1029-2403, Vol. 55, no 12, p. 2769-2777Article in journal (Refereed)
    Abstract [en]

    We conducted a randomized phase III trial to compare the efficacy and safety of two purine analogs, cladribine and fludarabine, with high-dose chlorambucil, in patients with previously untreated chronic lymphocytic leukemia (CLL). Between 1997 and 2004, 223 patients with CLL were randomly assigned to cladribine, fludarabine or chlorambucil, for six cycles of therapy with frequent health-related quality of life assessments. There was no statistical difference for the primary endpoint of overall response with cladribine (70%), fludarabine (67%) and chlorambucil (59%), or complete remission (12%, 7% and 8%), respectively. However, the median progression-free survival (25, 10, 9 months) and median time to second treatment (40, 22, 21 months) were superior with cladribine. There was no significant difference in overall survival (96, 82 and 91 months), nor in toxicity or HRQoL assessments. Monotherapy with cladribine gives superior PFS and longer response duration than fludarabine and chlorambucil as first-line treatment of CLL.

  • 32. Panagopoulos, Ioannis
    et al.
    Fioretos, Thoas
    Isaksson, Margareth
    Mitelman, Felix
    Johansson, Bertil
    Theorin, Niklas
    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.
    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.
    RT-PCR analysis of acute myeloid leukemia with t(8,16)(p11,p13): Identification of a novel MOZ/CBP transcript and absence of CBP/MOZ expression [1]2002In: Genes, Chromosomes and Cancer, ISSN 1045-2257, E-ISSN 1098-2264, Vol. 35, no 4, p. 372-374Article in journal (Refereed)
    Abstract [en]

    [No abstract available]

  • 33. Storlazzi, Clelia T
    et al.
    Fioretos, Thoas
    Paulsson, Kajsa
    Strömbeck, Bodil
    Lassen, Carin
    Ahlgren, Tomas
    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.
    Mitelman, Felix
    Rocchi, Mariano
    Johansson, Bertil
    Identification of a commonly amplified 4.3 Mb region with overexpression of C8FW, but not MYC in MYC-containing double minutes in myeloid malignancies2004In: Human Molecular Genetics, ISSN 0964-6906, E-ISSN 1460-2083, Vol. 13, no 14, p. 1479-1485Article in journal (Refereed)
    Abstract [en]

    Double minutes (dmin), the cytogenetic hallmark of genomic amplification, are found in ∼1% of karyotypically abnormal acute myelold leukemias (AML) and myelodysplastic syndromes (MDS). The MYC gene at 8q24 has been reported to be amplified in the majority of the cases, and generally it has been assumed that MYC is the target gene. However, only a few studies have focused on the extent of the amplicon or on the expression patterns of the amplified genes. We have studied six cases (five AML and one MDS) with MYC-containing dmin. Detailed fluorescence in situ hybridization analyses identified a common 4.3 Mb amplicon, with clustered proximal and distal breakpoints, harboring eight known genes (C8FW, NSE2, POU5FLC20, MYC, PVT1, AK093424, MGC27434 and MLZE). The corresponding region was deleted in one of the chromosome 8 homologues in five of the six cases, suggesting that the dmin originated through extra replication (or loop-formation)-excision-amplification. Northern blot analysis revealed that MYC was not overexpressed. Instead, the C8FW gene, encoding a phosphoprotein regulated by mitogenic pathways, displayed increased expression. These results exclude MYC as the target gene and indicate that overexpression of C8FW may be the functionally important consequence of 8q24 amplicons in AML and MDS. © Oxford University Press 2004, all rights reserved.

  • 34.
    Söderholm, Johan D
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Surgery . Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    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.
    Sjödahl, Rune
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Surgery . Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Long-term endoscopic remission in a case of Crohn's disease after autologous bone marrow transplantation.2000In: Gastroenterology, ISSN 0016-5085, E-ISSN 1528-0012, Vol. 118, no 4, p. 4212-Conference paper (Other academic)
  • 35.
    Söderholm, Johan D
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Surgery. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    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.
    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.
    Sjödahl, Rune
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Surgery. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Long-term endoscopic remission of Crohn disease after autologous stem cell transplantation for acute myeloid leukaemia2002In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 37, no 5, p. 613-616Article in journal (Refereed)
    Abstract [en]

    A favourable course of Crohn disease has been observed after allogeneic bone marrow transplantation, and there is now mounting evidence that autologous stem cell may be an effective treatment for severe autoimmune diseases. Here, we present the first long-term endoscopic follow-up of a patient with Crohn disease undergoing autologous stem cell transplantation for haematological disease. A 54-year-old woman developed Crohn disease and was submitted to ileocaecal resection. Four months after surgery, the patient contracted acute myeloid leukaemia. She was initially treated with chemotherapy, and subsequently underwent autologous stem cell transplantation. Following transplantation, the patient has remained in clinical remission regarding both diseases, without anti-inflammatory medication. She has undergone ileo-colonoscopy with normal findings at 1, 2, 3 and 5 years after transplantation. This case suggests that autologous stem cell transplantation can change not only the clinical course, but also the natural history of intestinal inflammation in Crohn disease. This has pathophysiological as well as therapeutic implications.

  • 36. Tidefelt, U
    et al.
    Liliemark, J
    Gruber, A
    Sundman-Engberg, B
    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.
    Stenke, L
    Elmhorn-Rosenborg, A
    Möllgård, L
    Lehman, S
    Xu, D
    Covelli, A
    Gustavsson, B
    Paul, C
    Liliemark, E
    P-glycoprotein inhibitor valspodar (PSC 833) increases the intracellular concentrations of Deunorubicin in vivo in patients with P-glycoprotein-positive acute myeloid leukemia.2000In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 18, p. 1837-1844Article in journal (Refereed)
  • 37. Tobin, G
    et al.
    Thunberg, U
    Johnson, A
    Eriksson, I
    Soderberg, O
    Karlsson, K
    Merup, M
    Enblad, G
    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.
    Vilpo, J
    Sundstrom, C
    Roos, G
    Rosenquist, R
    V(a)3-21 gene utilizing chronic lymphocytic leukemias display restricted V lambda 2-14 gene usage and homologous CDR3s.2002In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 100, no 11, p. 362-Conference paper (Other academic)
  • 38. Tobin, G
    et al.
    Thunberg, U
    Johnson, A
    Eriksson, I
    Soderberg, O
    Karlsson, Karin
    Linköping University, Department of Biomedicine and Surgery, Hematology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology.
    Merup, 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.
    Vilpo, J
    Enblad, G
    Sundstrom, C
    Roos, G
    Rosenquist, R
    Chronic lymphocytic leukemias utilizing the V(H)3-21 gene display highly restricted V(lambda)2-14 gene use and homologous CDR3s: implicating recognition of a common antigen epitope2003In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 101, no 12, p. 4952-4957Article in journal (Refereed)
    Abstract [en]

    The immunoglobulin variable heavy chain (IgV(H)) gene mutation status is an important prognostic factor in chronic lymphocytic leukemia (CLL), since cases with mutated V-H genes show significantly longer survival than unmutated cases. Recently, we reported a preferential use of the V(H)3-21 gene in mutated CLL and showed that mutated V(H)3-21 cases had an inferior overall survival compared with other mutated CLL. In order to further characterize this subset, we performed VH gene analysis in 265 CLL cases and identified 31 V(H)3-21 cases (11.7%), 21 cases had mutated and 10 cases unmutated VH genes. Regardless Of VH gene mutation status, a poor overall survival was found in the VH3-21 cases with a median survival of 83 months. These survival data confirm that V(H)3-21 cases do not fit into the general prognostic grouping of mutated and unmutated CLL. A large fraction Of V(H)3-21 cases also demonstrated unique features with shorter lengths of the third complementarity determining region (CDR3) and CDR3s with highly homologous amino acid sequences. Furthermore, the V(H)3-21 cases showed a striking dominance of X light chain expression, and analysis of the Iglambda gene rearrangements revealed highly restricted use of the Vlambda2-14/J(lambda)3 genes in the majority of cases. Taken together, our new findings strengthen the suggestion that V(H)3-21-using cases comprise a new CLL entity, irrespective Of VH gene mutation status, and implicate that a common antigen epitope, perhaps of pathogenic significance, is recognized by the highly homologous V(H)3-21/V(lambda)2-14 Ig molecules expressed in individual tumors. (Blood. 2003,101:4952-4957).

  • 39. Tobin, Gerard
    et al.
    Thunberg, Ulf
    Karlsson, Karin
    Murray, Fiona
    Laurell, Anna
    Willander, Kerstin
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology.
    Enblad, Gunilla
    Merup, Mats
    Vilpo, Juhani
    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.
    Sundström, Christer
    Söderberg, Ola
    Roos, Göran
    Rosenquist, Richard
    Subsets with restricted immunoglobulin gene rearrangement features indicate a role for antigen selection in the development of chronic lymphocytic leukemia2004In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 104, p. 2879-2885Article in journal (Refereed)
  • 40. Waage, A
    et al.
    Romstad, L
    Brenne, AT
    Gimsing, P
    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.
    Turesson, I
    Borset, M
    Sundan, A
    Low serum levels of soluble tumor necrosis factor receptors predict for response to thalidomide in advanced myeloma.2002In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 100, no 11, p. 5082-Conference paper (Other academic)
  • 41. Waage, Anders
    et al.
    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
    Gulbrandsen, Nina
    Eriksson, Tommy
    Hjorth, Martin
    Lanng Nielsen, Johan
    Lenhoff, Stig
    Westin, Jan
    Wislöff, Finn
    Early response predicts thalidomide efficiency in patients with advanced multiple myeloma2004In: British Journal of Haematology, ISSN 0007-1048, E-ISSN 1365-2141, Vol. 125, no 2, p. 149-155Article in journal (Refereed)
    Abstract [en]

    Sixty-five patients who were primary or secondary refractory to melphalan/ prednisone or other type of chemotherapy, or relapsed within 6 months after high dose chemotherapy with stem cell support, were given thalidomide at a dose of 200 mg/d escalating to 800 mg. The patients were followed for a median of 2 years and 22 weeks. Response was evaluated according to M-protein reduction combined with improvement of haemoglobin (Hb) concentration, renal function and pain. Altogether, 14% of patients had a minor response, 14% partial response and 6% complete response. Median survival was 12 months and 29% were alive at last contact. Decline of M protein started early and a minimum 25% reduction of M protein was detected in 14 of 20 responders (70%) after 3 weeks, and in 20 of 22 responders (91%) after 5 weeks of treatment. Reduction of M protein continued for 3 months and further decline was observed in only four patients. The Hb concentration showed a different time course, with a significant increase after 3 months and further increases continued for up to 12 months. Blood concentration levels of thalidomide from 40 patients were used to evaluate the pharmacokinetics of the drug. Rate of absorption, rate of elimination, volume of distribution, clearance and elimination half-life were calculated to be 0.200/h, 0.140/h, 0.886 l/kg, 0.126 l/h/kg and 4.98 h respectively. We found no relationship between thalidomide concentration and effect after 12 weeks.

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